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  1. Development and clinical course of diseases accompanied by connective tissue dysplasia in children of puberty age

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    Elizarova S.Yu.

    2011-03-01

    Full Text Available The risk of development and clinical course of somatic diseases have been analyzed in the research work. 111 adolescents suffering from connective tissue dysplasia have been under the study. It has been stated that the frequency of somatic diseases among adolescents with connective tissue dysplasia is higher than this frequency among adolescents without such disease. Phenotypic signs of connective tissue dysplasia have been revealed. They are responsible for the development of bronchial asthma and severe stomach ulcer

  2. [Pulmonary involvement in connective tissue disease].

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    Bartosiewicz, Małgorzata

    2016-01-01

    The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

  3. The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

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    Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

    2017-12-01

    In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

  4. Morphological, clinical and radiological aspects in diagnostics of bronchopulmonary diseases and their complications in children with dysplasia of connective tissue

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    Palchik S.M.

    2016-06-01

    Full Text Available The article provides an overview of the literature devoted to study of radiological, morphological and clinical aspects of diagnostics of respiratory diseases and their complications in children with dysplasia of connective tissue nowadays. We made an analysis of the role of connective tissue disorders in pathogenesis of bronchopulmonary diseases. Theoretically was substantiated the importance of radiological methods in early diagnostics of this disease in children.

  5. Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease.

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    Kong, Eric F; Kucharíková, Sona; Van Dijck, Patrick; Peters, Brian M; Shirtliff, Mark E; Jabra-Rizk, Mary Ann

    2015-02-01

    The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV(+) and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Undifferentiated Connective Tissue Disease

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    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  7. Celiac disease: clinical observations

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    Yu. A. Emel’yanova

    2016-01-01

    Full Text Available Presented clinical cases of patients with a diagnosis of gluten enteropathy in treatment in the department of gastroenterology Regional Clinical Hospital. The case is of interest to doctors of different specialties for the differential diagnosis of anemia and malabsorption syndrome, demonstrate both the classic version, and atypical forms of the disease course. Diagnosis of celiac disease is based on three key positions: clinical findings, histology and serological markers. The clinical picture of celiac disease is characterized by pronounced polymorphism, by going beyond the a gastroenterological pathology. For screening of gluten sensitive celiac typically used an antibody to tissue transglutaminase. Morphological research of the mucous membrane of the small intestine is the determining criterion in the diagnosis of celiac disease. The use of specific gluten-free diet leads to the positive dynamics of the disease and improve the quality of life of patients.

  8. Mixed Connective Tissue Disease

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    Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

  9. Oral manifestations of connective tissue disease and novel therapeutic approaches.

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    Heath, Kenisha R; Rogers, Roy S; Fazel, Nasim

    2015-10-16

    Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

  10. [Mixed connective tissue disease: prevalence and clinical characteristics in African black, study of 7 cases in Gabon and review of the literature].

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    Missounga, Landry; Ba, Josaphat Iba; Nseng Nseng Ondo, Ingrid Rosalie; Nziengui Madjinou, Maria Ines Carine; Malekou, Doris; Mouendou Mouloungui, Emeline Gracia; Nzengue, Emmanuel Ecke; Boguikouma, Jean Bruno; Kombila, Moussavou

    2017-01-01

    The literature reports that mixed connective tissue disease seems more frequent in the black population and among Asians. This study aims to determine the prevalence of mixed connective tissue disease (MCTD) among connective tissue disorders and all rheumatologic pathologies in a hospital population in Gabon as well as to describe the clinical features of this disease. We conducted a retrospective study by reviewing the medical records of patients treated for mixed connective tissue disease (Kasukawa criteria) and other entities of connective tissue disorders (ACR criteria) in the Division of Rheumatology at the University Hospital in Libreville between January 2010 and December 2015. For each case of MCTD the parameters studied were articular and extra-articular manifestations, anti-U1RNP antibodies levels, patient's evolution. Over a period of 6 years, data were collected by medical records of 7 patients out of 6050 patients and 67 cases of connective tissue disorders, reflecting a prevalence of 0.11% and 10.44% respectively. the 7 patients were women (100%), with an average age of 39.5 years. Articular manifestations included: polyarthritis, myalgias, chubby fingers and Raynaud's phenomenon in 87.5%, 87.5%, 28.6% and 14% respectively. The 7 patients had high anti-U1RNP antibodies levels, ranging between 5 and 35N (N≤ 7 IU). A case of death due to pulmonary arterial hypertension (PAH) was certified. This is the largest case series of MCTD reported in Black Africa. The disease seems to be rare among the black Africans; the reason could be genetic. The demographic and clinical aspects appear similar to those in Caucasians, Asians and Blacks except for a low frequency of Raynaud?s phenomenon among Blacks.

  11. Clinical use of fungal PCR from deep tissue samples in the diagnosis of invasive fungal diseases: a retrospective observational study.

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    Ala-Houhala, M; Koukila-Kähkölä, P; Antikainen, J; Valve, J; Kirveskari, J; Anttila, V-J

    2018-03-01

    To assess the clinical use of panfungal PCR for diagnosis of invasive fungal diseases (IFDs). We focused on the deep tissue samples. We first described the design of panfungal PCR, which is in clinical use at Helsinki University Hospital. Next we retrospectively evaluated the results of 307 fungal PCR tests performed from 2013 to 2015. Samples were taken from normally sterile tissues and fluids. The patient population was nonselected. We classified the likelihood of IFD according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG), comparing the fungal PCR results to the likelihood of IFD along with culture and microscopy results. There were 48 positive (16%) and 259 negative (84%) PCR results. The sensitivity and specificity of PCR for diagnosing IFDs were 60.5% and 91.7%, respectively, while the negative predictive value and positive predictive value were 93.4% and 54.2%, respectively. The concordance between the PCR and the culture results was 86% and 87% between PCR and microscopy, respectively. Of the 48 patients with positive PCR results, 23 had a proven or probable IFD. Fungal PCR can be useful for diagnosing IFDs in deep tissue samples. It is beneficial to combine fungal PCR with culture and microscopy. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Coeliac disease - clinical presentation and diagnosis by anti tissue transglutaminase antibodies titre in children

    International Nuclear Information System (INIS)

    Hussain, S.; Sabir, M.U.D.; Afzal, M.; Asghar, I.

    2014-01-01

    Objective: To study the spectrum of clinical presentation of coeliac disease and the role of IgA anti-tissue transglutaminase antibodies titer in the diagnosis and effect of gluten-free diet on such titers in children. Methods: The prospective study was conducted in the paediatric department of Combined Military Hospital, Kharian from Sep 2011 to Sep 2012. Children of 1-12 years of age presenting with chronic diarrhoea, malnutrition and failure to thrive were included regardless of gender, socioeconomic status, ethnicity and geographical distribution. Anti-tissue transglutaminase antibodies titers were done on enrolment. Patients with levels more than 30u/ml were enrolled. They were advised strict gluten-free diet for six months. These titers were repeated after six months to document the effect of gluten-free diet on these titers. Paediatric endoscopy and duodenal biopsy facilities were not available at the study site, so the response was monitored through titers. Data was analysed using SPSS-20. Results: Out of 61 patients with IgA levels more than 10 u/ml, 52 (85.24%) were found to have a positive (>30u/ml) anti-tissue transglutaminase antibodies titers with a mean value of 42.67+-7.60 U/ml. These 52 patients were then put on a trial of gluten-free diet for six months after which significant reduction in titer was noticed, with a mean value of 13.25+-2.59 U/ml. This reduction in titer was associated with marked clinical improvement and regression of symptoms. Frequency of different clinical features in descending order revealed that chronic diarrhoea, abdominal distension, iron deficiency anaemia, failure to thrive, pallor and rickets were present in 38 (73.1%), 30 (57.7%), 29 (55.8%), 29 (53.8%), 28 (53.8%) patients respectively. Conclusion: Chronic diarrhoea, failure to thrive, pallor, abdominal distention and iron deficiency anaemia were common modes of presentation. The antibodies were strongly positive in most of the cases. All children showed significant

  13. MRI evaluation of soft tissue hydatid disease

    International Nuclear Information System (INIS)

    Garcia-Diez, A.I.; Ros Mendoza, L.H.; Villacampa, V.M.; Cozar, M.; Fuertes, M.I.

    2000-01-01

    Infestation in soft tissue by Echinococcus granulosus is not a common disease, and its diagnosis is based on clinical, laboratory data and radiological findings. The aim of our retrospective study is to give an overview of the different signs and patterns shown by MRI that can be useful in characterizing soft tissue hydatid disease. The MRI images obtained in seven patients with soft tissue and subcutaneous hydatidosis were reviewed. Typical signs of hydatidosis were multivesicular lesions with or without hypointense peripheral ring (''rim sign''). Related to the presence and absence, respectively, of viable scolices in the microscopic exam, daughter cysts were presented either as high signal intensity or low signal intensity on T2-weighted images. Low-intensity detached layers within the cyst and peripheral enhancement with gadolinium-DTPA were also presented. Atypical signs were presented in an infected muscular cyst, a subcutaneous unilocular cyst and several unilocular cysts. Knowledge of the different patterns in MRI of soft tissue hydatid disease can be useful in diagnosing this entity. We observed that the ''rim sign'' is not as common as in other locations, and in addition, MRI seems to be of assistance when evaluating the vitality of the cysts. (orig.)

  14. Interstitial lung disease associated with connective tissue diseases

    International Nuclear Information System (INIS)

    Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

    2007-01-01

    An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

  15. MRI evaluation of soft tissue hydatid disease

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    Garcia-Diez, A.I.; Ros Mendoza, L.H.; Villacampa, V.M.; Cozar, M.; Fuertes, M.I. [Dept. of Radiology, Hospital Miguel Servet, Zaragoza (Spain)

    2000-03-01

    Infestation in soft tissue by Echinococcus granulosus is not a common disease, and its diagnosis is based on clinical, laboratory data and radiological findings. The aim of our retrospective study is to give an overview of the different signs and patterns shown by MRI that can be useful in characterizing soft tissue hydatid disease. The MRI images obtained in seven patients with soft tissue and subcutaneous hydatidosis were reviewed. Typical signs of hydatidosis were multivesicular lesions with or without hypointense peripheral ring (''rim sign''). Related to the presence and absence, respectively, of viable scolices in the microscopic exam, daughter cysts were presented either as high signal intensity or low signal intensity on T2-weighted images. Low-intensity detached layers within the cyst and peripheral enhancement with gadolinium-DTPA were also presented. Atypical signs were presented in an infected muscular cyst, a subcutaneous unilocular cyst and several unilocular cysts. Knowledge of the different patterns in MRI of soft tissue hydatid disease can be useful in diagnosing this entity. We observed that the ''rim sign'' is not as common as in other locations, and in addition, MRI seems to be of assistance when evaluating the vitality of the cysts. (orig.)

  16. Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

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    Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

    2018-02-01

    Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

  17. Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease Prions in Tissues of Clinical and Asymptomatic Patients.

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    Douet, Jean Y; Lacroux, Caroline; Aron, Naima; Head, Mark W; Lugan, Séverine; Tillier, Cécile; Huor, Alvina; Cassard, Hervé; Arnold, Mark; Beringue, Vincent; Ironside, James W; Andréoletti, Olivier

    2017-06-01

    In the United-Kingdom, ≈1 of 2,000 persons could be infected with variant Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by medical procedures remains a major concern for public health authorities. In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. PMCA identified major levels of vCJD prions in a range of tissues, including liver, salivary gland, kidney, lung, and bone marrow. Bioassays confirmed that the quantitative estimate of levels of vCJD prion accumulation provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings provide critical data for the design of measures to minimize risk for iatrogenic transmission of vCJD.

  18. Tissue banking and clinical research on radiation and ethylene oxide sterilization of tissue grafts

    International Nuclear Information System (INIS)

    Pe Khin

    1987-06-01

    The research works carried out in Rangoon, Burma under the Agency supported project RC4420/RB have dealt with an elucidation of the radiation interaction(s) with the species of biomolecules such as proteins, lipids, collagens, connective tissues present in the cleaned and freeze-dried non-viable tissue grafts. Radiation as a cool process furthermore effectively helps to destroy the microbial bioburden as the undesirable contaminants which may associate the tissue grafts. Radiation also concomitantly helps to suppress the tissue-specific immunogenicity. All these attributes of radiation induced effects have proved successful towards the development of a sterilization process. A series of non-viable tissue grafts, such as bone, nerve, fascia, dura, cartilage, chorion-amnion (as dressings in burn wounds) and tympanic membrane have been successfully attempted in Burma and many more possibilities seem to still remain unexplored. Radiation sterilization modality has proved as a blessing for the promotion of clinical surgical applications of tissue allografts in the corrective/reconstructive surgery on the disability cases due to diseases which accompany tissue losses. The investigator in Burma has reported on the case histories where freeze dried radiation sterilized tissue allografts have been successfully used in the osteogenic inductions (bone grafts); midear tympanoplasty; partial recovery of nerve sensation throught nerve allografts; rapid healing of high degree burn wounds through the use of amnion dressings. Besides, there have been a widespread surgical use of radiation sterilized dura and fascia as allografts. A national tissue banking facility has been established in Burma surrounding the processing and clinical utilization of tissue allografts which has involved over ten hospital centres throughout the country. Radiation induced effects on the biomolecules of clinical significance in the tissue grafts have been researched to help gain insight into a better

  19. Clinically Unsuspected Prion Disease Among Patients With Dementia Diagnoses in an Alzheimer's Disease Database.

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    Maddox, Ryan A; Blase, J L; Mercaldo, N D; Harvey, A R; Schonberger, L B; Kukull, W A; Belay, E D

    2015-12-01

    Brain tissue analysis is necessary to confirm prion diseases. Clinically unsuspected cases may be identified through neuropathologic testing. National Alzheimer's Coordinating Center (NACC) Minimum and Neuropathologic Data Set for 1984 to 2005 were reviewed. Eligible patients had dementia, underwent autopsy, had available neuropathologic data, belonged to a currently funded Alzheimer's Disease Center (ADC), and were coded as having an Alzheimer's disease clinical diagnosis or a nonprion disease etiology. For the eligible patients with neuropathology indicating prion disease, further clinical information, collected from the reporting ADC, determined whether prion disease was considered before autopsy. Of 6000 eligible patients in the NACC database, 7 (0.12%) were clinically unsuspected but autopsy-confirmed prion disease cases. The proportion of patients with dementia with clinically unrecognized but autopsy-confirmed prion disease was small. Besides confirming clinically suspected cases, neuropathology is useful to identify unsuspected clinically atypical cases of prion disease. © The Author(s) 2015.

  20. Epicardial adipose tissue in endocrine and metabolic diseases.

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    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  1. Immersion radiography for enhancement of soft tissue contrast - experimental study and clinical application -

    International Nuclear Information System (INIS)

    Lee, Kyung Soo; Kang, Heung Sik; Kim, Chu Wan

    1986-01-01

    Detection and evaluation of early soft tissue changes are important in rheumatoid arthritis or other joint diseases. The most important factors for radiologic demonstration of soft tissue changes are resolving power and the optimization of contrast differences between structures representing skin and subcutaneous tissue densities. Phantom study was done by using combination of immersion technique and mammography to get the most reliable method for improvement of soft tissue contrast without deterioration of resolution. Clinical application was also done in 5 normal volunteers and 5 rheumatoid patients. The results indicate that soft tissue contrast, especially between skin and subcutaneous tissues can be significantly improved with combination of immersion technique and mammography with 50% ethanol in both phantom and clinical study.

  2. Nail unit in collagen vascular diseases: A clinical, histopathological and direct immunofluorescence study

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    Nabil P

    2006-01-01

    Full Text Available Background: Abnormalities of the nail unit are common in patients with connective tissue diseases. Clinical examination of the nail unit, coupled with biopsy of proximal nail fold offers an additional advantage in the diagnosis. Purpose: Our aim was to record clinical changes of the nail unit in connective tissue diseases and to study the histopathological (both H and E and periodic acid Schiff and direct immunofluorescence (DIF findings of nail-fold biopsy. Materials and Methods: Thirty-eight confirmed cases connective tissue diseases attending skin OPD were enrolled in the study. After detailed clinical examination of the nail unit, a crescentric biopsy was taken from the proximal nail fold (PNF. Histopathological and DIF studies were was carried out. Findings: Nail changes could be demonstrated in 65% connective tissue diseases. Specific histopathological (H and E and immunofluorescence findings were also encountered in many patients. Conclusion: Clinical examination of the nail unit offers additional clue in the diagnosis of connective tissue diseases. Though DIF of PNF biopsy is useful in the diagnosis, it is not an ideal site for H and E study, as the yield is very low. Limitations: Lack of adequate comparison group and non-utilization of capillary microscopy for the detection of nail fold capillary abnormalities.

  3. On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors

    International Nuclear Information System (INIS)

    Terui, Shoji; Terauchi, Takashi; Abe, Hiroyuki; Fukuma, Hisatoshi; Beppu, Yasuo; Chuman, Koichi; Yokoyama, Ryohei

    1994-01-01

    The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201 (81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas. (author)

  4. Radiotherapy in patients with connective tissue diseases.

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    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Scleroderma renal crisis in a case of mixed connective tissue disease

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    Mukul Vij

    2014-01-01

    Full Text Available Mixed connective tissue disease (MCTD is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma and polymyositis. Scleroderma renal crisis (SRC is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  6. Scleroderma renal crisis in a case of mixed connective tissue disease.

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    Vij, Mukul; Agrawal, Vinita; Jain, Manoj

    2014-07-01

    Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  7. Imaging of connective tissue diseases of the head and neck

    Science.gov (United States)

    2016-01-01

    We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

  8. Dudrick Research Symposium 2015-Lean Tissue and Protein in Health and Disease.

    Science.gov (United States)

    Earthman, Carrie P; Wolfe, Robert R; Heymsfield, Steven B

    2017-02-01

    The 2015 Dudrick Research Symposium "Lean Tissue and Protein in Health and Disease: Key Targets and Assessment Strategies" was held on February 16, 2015, at Clinical Nutrition Week in Long Beach, California. The Dudrick Symposium honors the many pivotal and innovative contributions to the development and advancement of parenteral nutrition made by Dr Stanley J. Dudrick, physician scientist, academic leader, and a founding member of the American Society for Parenteral and Enteral Nutrition. As the 2014 recipient of the Dudrick award, Dr Carrie Earthman chaired the symposium and was the first of 3 speakers, followed by Dr Robert Wolfe and Dr Steven Heymsfield. The symposium addressed the importance of lean tissue to health and response to disease and injury, as well as the many opportunities and challenges in its assessment at the bedside. Lean tissue assessment is beneficial to clinical care in chronic and acute care clinical settings, given the strong relationship between lean tissue and outcomes, including functional status. Currently available bioimpedance techniques, including the use of bioimpedance parameters, for lean tissue and nutrition status assessment were presented. The connection between protein requirements and lean tissue was discussed, highlighting the maintenance of lean tissue as one of the most important primary end points by which protein requirements can be estimated. The various tracer techniques to establish protein requirements were presented, emphasizing the importance of practical considerations in research protocols aimed to establish protein requirements. Ultrasound and other new and emerging technologies that may be used for lean tissue assessment were discussed, and areas for future research were highlighted.

  9. Facts and controversies in mixed connective tissue disease.

    Science.gov (United States)

    Martínez-Barrio, Julia; Valor, Lara; López-Longo, F Javier

    2018-01-12

    Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

    Science.gov (United States)

    Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

    2018-01-03

    Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

  11. Clinical management of soft tissue sarcomas

    International Nuclear Information System (INIS)

    Pinedo, H.M.; Verweij, J.

    1986-01-01

    This book is concerned with the clinical management of soft tissue sarcomas. Topics covered include: Radiotherapy; Pathology of soft tissue sarcomas; Surgical treatment of soft tissue sarcomas; and Chemotherapy in advanced soft tissue sarcomas

  12. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  13. Clinical neurorestorative progress in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen L

    2015-06-01

    Full Text Available Lin Chen,1,2 Hongyun Huang,3–5 Wei-Ming Duan,6 Gengsheng Mao3 1Department of Neurosurgery, Yuquan Hospital, Tsinghua University, 2Department of Neurosurgery, Medical Center, Tsinghua University, 3Department of Neurosurgery, General Hospital of Chinese People's Armed Police Forces, 4Center of Cell Research, Beijing Rehabilitation Hospital of Capital Medical University, 5Beijing Hongtianji Neuroscience Academy, 6Department of Anatomy, Capital Medical University, Beijing, People's Republic of China Abstract: Parkinson’s disease (PD is one of the common neurodegenerative diseases. Besides the symptomatic therapies, the increasing numbers of neurorestorative therapies have shown the potential therapeutic value of reversing the neurodegenerative process and improving the patient's quality of life. Currrently available novel clinical neurorestorative strategies include pharmacological managements (glial cell-line derived neurotrophic factor, selegiline, recombinant human erythropoietin, neuromodulation intervention (deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, tissue and cell transplantation (fetal ventral mesencephalic tissue, sympathetic neurons, carotid body cells, bone marrow stromal cells, retinal pigment epithelium cells, gene therapy, and neurorehabilitative therapy. Herein, we briefly review the progress in this field and describe the neurorestorative mechanisms of the above-mentioned therapies for PD. Keywords: Parkinson’s disease, clinical study, neurorestorative treatment, cell transplantation, neuromodulation

  14. Soft tissue manifestations of early rheumatic disease. Imaging with MRI

    International Nuclear Information System (INIS)

    Treitl, M.; Panteleon, A.; Koerner, M.; Becker-Gaab, C.; Reiser, M.; Wirth, S.

    2006-01-01

    The aim of this study was to evaluate typical magnetic resonance imaging (MRI) findings in early rheumatic diseases manifesting at the soft tissues of the hand using a retrospective analysis. A total of 186 MRI examinations of patients with clinical suspicion of a rheumatic disease were evaluated in a consensus reading by two experienced radiologists. All imaging patterns were assessed with respect to their type and localization. Under blinded and non-blinded conditions diagnoses were correlated with final clinical diagnosis. The most frequent diagnoses were rheumatoid arthritis (RA, 45.7%) and psoriatic arthritis (PsA, 15.6%). The mean correlation between clinical and MRI diagnosis (r) was 0.75 in blinded and 0.853 in non-blinded reading (p [de

  15. FEATURES OF CLINICAL COURSE OF GASTROESOPHAGEAL REFLUX DISEASE IN NEWLY RECRUITED WITH CONNECTIVE TISSUE UNDIFFERENTIATED DYSPLASIA SYNDROME

    Directory of Open Access Journals (Sweden)

    E.I. Kashkina

    2008-12-01

    Full Text Available The presence of connective tissue undifferentiated dysplasia syndrome against a background of psychological stress at newly recruited can promote the risk of gastroesophageal reflux disease occurrence. To the utmost, correlation between the gastroesophageal reflux disease and such manifestations of connective tissue undifferentiated dysplasia syndrome as asthenic constitution, chest deformation, Gothic palate and hypermobility of joints was found

  16. Connective tissue diseases, multimorbidity and the ageing lung.

    Science.gov (United States)

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

  17. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2016-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  18. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2009-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  19. Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

    Science.gov (United States)

    O'Keefe, Regis J; Mao, Jeremy

    2011-12-01

    A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

  20. Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

    Science.gov (United States)

    Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

    2009-06-01

    Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

  1. Pregnancy and autoimmune connective tissue diseases

    Science.gov (United States)

    Marder, Wendy; Littlejohn, Emily A

    2016-01-01

    The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  2. Ineffectiveness of rat liver tissues in the screening of connective tissue disease

    International Nuclear Information System (INIS)

    Aziz, Khalil A.

    2004-01-01

    To assess the effectiveness of using rat liver tissue (RLT) for the screening of connective tissue disease (CTD). Results of patient samples submitted to the Clinical Immunology Laboratory, Brimingham Heartlands Hospital, Bordsley Green East, Brimingham, United Kingdom for the investigation of CTD between 2001 and 2002 were analyzed. Positive results for anti-double stranded DNA (dsDNA) antibodies and anti-extractable nuclear antigen (ENA) antibodies were correlated with the results of the corresponding antinuclear antibodies (ANA), obtained by indirect immunofluorescence (IIF) using RLT. In the second part of study samples that were previously tested positive for anti-ENA or anti-dsDNA antibodies were investigated prospectively for ANA using both RLTand human epithelial (Hep-2) cell line. The IIF method employing RLT for screening of CTD, failed to detect ANA patterns from 45% and 25%of patients sample know to contain antibodies to dsDNA and ENA.The anti -dsDNA antibodies that failed to be detected by the RLTwere of low avidity and their clinical significance is unknown. In contrast the antibodies to ENAwere mostly directed against the Ro antigen.In cotrast and like RLT, Hep-2 cell line failed to detect the low avidity anti-dsDNA antibdies.The present study has clearly shown that RLT are ineffective for screening of CTD. It is recommended that laboratories which ars still using these tissues should consider replacing them with the Hep-2 cell line. (author)

  3. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    International Nuclear Information System (INIS)

    Burkhardt, W.C.; Jackson, J.F.; Songcharoen, S.; Meydrech, E.F.

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05). (author)

  4. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Burkhardt, W C; Jackson, J F; Songcharoen, S; Meydrech, E F [Mississippi Univ., Jackson (USA). Medical Center

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05).

  5. Morphometric assessment of periodontal tissues in relation to periodontal disease in dogs.

    Science.gov (United States)

    Kyllar, Michal; Doskarova, Barbora; Paral, Vaclav

    2013-01-01

    Dimensions of periodontal tissues are thought to predispose to the development of periodontal disease in man and dogs. Several studies have suggested that thin gingiva correlates with an increased incidence of periodontal disease. In this study, we hypothesized that the dimensions of periodontal tissues will vary in different breeds of dogs and could possibly correlate with the incidence of periodontal disease. Forty-two jaws of dogs aged up to 5-years were examined post-mortem and gingival and alveolar bone thickness were measured using methods of transgingival probing and digital calipers, respectively. Dogs were divided into three groups based on their body weight. Group I (dogs compared with small and medium-sized breed dogs. Both gingival and alveolar bone dimensions may be predictors for severity of periodontal disease and influence clinical outcome in certain periodontal surgical procedures.

  6. Heat-shock proteins in stromal joint tissues: innocent bystanders or disease-initiating proteins?

    Science.gov (United States)

    Lambrecht, Stijn; Juchtmans, Nele; Elewaut, Dirk

    2014-02-01

    Heat-shock proteins (HSPs) are molecular chaperones that are highly conserved between species. In recent decades it has become clear that these proteins play an important role in the pathogenesis of inflammatory and degenerative joint diseases by (dys)regulating the immune system and by direct effects on the stromal tissues of the joint. In this review we discuss current insights into the expression pattern of HSPs in connective tissues, the direct biological role of HSPs in stromal tissues and the potential clinical applications.

  7. New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

    Institute of Scientific and Technical Information of China (English)

    Charles H Knowles; Joanne E Martin

    2009-01-01

    Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

  8. Oral soft tissue disorders are associated with gastroesophageal reflux disease: retrospective study.

    Science.gov (United States)

    Watanabe, Masaaki; Nakatani, Eiji; Yoshikawa, Hiroo; Kanno, Takahiro; Nariai, Yoshiki; Yoshino, Aya; Vieth, Michael; Kinoshita, Yoshikazu; Sekine, Joji

    2017-08-07

    Dental erosion (DE), one of oral hard tissue diseases, is one of the extraoesophageal symptoms defined as the Montreal Definition and Classification of gastroesophageal reflux disease (GERD). However, no study evaluated the relationship between GERD and oral soft tissues. We hypothesized that oral soft tissue disorders (OSTDs) would be related to GERD. The study aimed to investigate the association OSTDs and GERD. GERD patients (105 cases), older and younger controls (25 cases each) were retrospectively examined for oral symptoms, salivary flow volume (Saxon test), swallowing function (repetitive saliva swallowing test [RSST]), teeth (decayed, missing, and filled [DMF] indices), and soft tissues (as evaluation of OSTDs, gingivitis; papillary, marginal, and attached [PMA] gingival indexes, simplified oral hygiene indices [OHI-S], and inflammatory oral mucosal regions). Clinical histories, which included body mass index [BMI], the existence of alcohol and tobacco use, and bruxism, were also investigated. A P value of bruxism, as an exacerbation factor of periodontal disease, in the GERD patients was significantly more frequent than in either control group (P = 0.041). OSTDs were associated with GERD, which was similar to the association between DE and GERD.

  9. Histopathology of lung disease in the connective tissue diseases.

    Science.gov (United States)

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. [CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

    Science.gov (United States)

    Madiyeva, M; Rymbayeva, T

    2017-11-01

    The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

  11. The establishment of a national tissue bank for inflammatory bowel disease research in Canada.

    Science.gov (United States)

    Collins, Stephen M; McHugh, Kevin; Croitoru, Ken; Howorth, Michael

    2003-02-01

    The Crohn's and Colitis Foundation of Canada (CCFC) has established a national bank for tissue, serum and blood from patients with inflammatory bowel disease (IBD). Investigators from across the country submit material to the bank together with clinical data. Investigators may access their own patient information from the bank for their own study purposes, but the distribution of tissue is restricted to specific CCFC-funded projects. Currently, tissues are being collected from newly diagnosed, untreated IBD patients to support a recent initiative aimed at characterizing microbes in colonic and ileal biopsies from such patients. In the future, criteria for the submission of tissue will be tailored to specific research questions. This bank is believed to be the first national bank of its kind dedicated to research in Crohn's disease and ulcerative colitis

  12. Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

    Science.gov (United States)

    Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

    To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  13. Significance of connective tissue diseases features in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2013-09-01

    Full Text Available Interstitial lung disease (ILD can occur in any of the connective tissue diseases (CTD with varying frequency and severity, and an overall long-term prognosis that is less severe than that of idiopathic pulmonary fibrosis (IPF. Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD. Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered “highly specific” of an autoimmune condition, but who do not fit with established international CTD criteria may be called undifferentiated CTD or “lung-dominant CTD”. Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.

  14. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The Establishment of a National Tissue Bank for Inflammatory Bowel Disease Research in Canada

    Directory of Open Access Journals (Sweden)

    Stephen M Collins

    2003-01-01

    Full Text Available The Crohn’s and Colitis Foundation of Canada (CCFC has established a national bank for tissue, serum and blood from patients with inflammatory bowel disease (IBD. Investigators from across the country submit material to the bank together with clinical data. Investigators may access their own patient information from the bank for their own study purposes, but the distribution of tissue is restricted to specific CCFC-funded projects. Currently, tissues are being collected from newly diagnosed, untreated IBD patients to support a recent initiative aimed at characterizing microbes in colonic and ileal biopsies from such patients. In the future, criteria for the submission of tissue will be tailored to specific research questions. This bank is believed to be the first national bank of its kind dedicated to research in Crohn’s disease and ulcerative colitis.

  16. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  17. Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.

    Science.gov (United States)

    Pérez-Merino, E M; Usón-Casaús, J M; Zaragoza-Bayle, C; Duque-Carrasco, J; Mariñas-Pardo, L; Hermida-Prieto, M; Barrera-Chacón, R; Gualtieri, M

    2015-12-01

    Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Foot-and-mouth disease virus infection in young lambs: pathogenesis and tissue tropism

    DEFF Research Database (Denmark)

    Ryan, Eoin; Horsington, Jacquelyn; Durand, Stephanie

    2008-01-01

    Foot-and-mouth disease (FMD) in adult sheep usually causes milder clinical signs than in cattle or pigs, and is often subtle enough to go undiagnosed. In contrast, FMD in lambs has been reported to cause high mortality during field outbreaks. In order to investigate the pathogenesis of FMD in lambs......, two groups, aged 10–14 days, were infected with foot-and-mouth disease virus (FMDV) type O UKG. One group of lambs (n = 8) was inoculated with FMDV in the coronary band, while the other (n = 4) was infected by direct contact with FMDV-inoculated ewes. Daily serum samples and temperature measurements...... were taken. Lambs were killed sequentially and tissue samples taken for analysis. Using real-time RT-PCR, viral RNA levels in tissue samples and serum were measured, and a novel strand-specific real-time RT-PCR assay was used to quantify viral replication levels in tissues. Tissue sections were...

  19. Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Paola Cordiali-Fei

    2013-01-01

    Full Text Available In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc and undifferentiated connective tissue disease (UCTD, we have explored the setting of peripheral T regulatory (T reg cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc or diffuse (dcSSc disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

  20. Radiosterilization of Tissues Preserved for Clinical Purposes: Effect on Tissue Antigenicity

    International Nuclear Information System (INIS)

    Ostrowski, K.; Kossowska, B.; Moskalewski, S.; Komender, A.; Kurnatowski, W.

    1967-01-01

    The first part of the paper contains practical considerations on the radiosterilization of preserved human bone, human and calf cartilage, cow’s fascia and aponeurosis, based on material from the Tissue Bank which produces about 2500 transplants yearly. The method of preservation and packing of each type of tissue is mentioned briefly. The preserved tissues are irradiated in a cobalt bomb or in a nuclear reactor. The conditions of irradiation and the control of sterility are described. The advantages and disadvantages of radiosterilization are discussed on the basis of the authors’ own experience and clinical reports of surgeons using radiosterilized tissues in practice. In the second part of the paper, experimental studies on the influence of freezing, lyophilization and radiosterilization on tissue antigenicity are reported. The regional lymph node reacts to an antigenic stimulus by an increased production of large, pyroninophylic cells, so-called ''blast'' cells. The rabbits used as recipients received grafts of allogeneic cancellous bone, fresh or subjected to different experimental procedures. Smears from lymph node cell suspension were prepared and the percentage of blast cells was estimated. On the basis of the lymph node response, it appears that freezing and lyophilization, as well as radiosterilization, may abolish the antigenicity of cancellous bone. The practical implication of these results for methods of preservation of tissues for clinical purposes is discussed. (author)

  1. Trace element determinations in brain tissues from normal and clinically demented individuals

    International Nuclear Information System (INIS)

    Saiki, Mitiko; Genezini, Frederico A.; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson

    2013-01-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  2. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  3. Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Anna Minchom

    2010-01-01

    Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

  4. An analysis of the clinical features of lung cancer in patients with connective tissue diseases.

    Science.gov (United States)

    Saijo, Atsuro; Hanibuchi, Masaki; Goto, Hisatsugu; Toyoda, Yuko; Tezuka, Toshifumi; Nishioka, Yasuhiko

    2017-03-01

    Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors. Forty-four LC patients without CTD were also analyzed as a control cohort. LC patients with CTD had a significantly higher incidence of ILD as a complication compared with those without CTD (52% and 14%, respectively). CTD-associated ILD (CTD-ILD) at diagnosis was associated with significantly worse survival in LC patients with CTD. Multivariate analysis demonstrated that the complication of CTD-ILD was an independent poor prognostic factor in LC patients with CTD. The incidence of acute exacerbation (AE) of CTD-ILD was 21% among LC patients with CTD, and all of these patients died despite intensive treatment including high-dose corticosteroids. The restrictions in curative therapy for LC due to the presence of ILD and AE of CTD-ILD were thought to be the major reasons for the poor outcome. LC patients with CTD had a high prevalence of ILD, and the presence of CTD-ILD was significantly associated with poor prognosis. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  5. Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

    Directory of Open Access Journals (Sweden)

    Renata Miossi

    2013-01-01

    Full Text Available OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1 virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0 and geometric mean titer (p = 0.83 between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7, seroconversion (68.1% vs. 65.2%, (p = 1.00 and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40 were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20, skin ulcers (p = 0.48, lupus-like cutaneous disease (p = 0.74, secondary Sjogren syndrome (p = 0.78, scleroderma-pattern in the nailfold capillaroscopy (p = 1.0, lymphopenia #1000/mm³ on two or more occasions (p = 1.0, hypergammaglobulinemia $1.6 g/d (p = 0.60, pulmonary hypertension (p = 1.0 and pulmonary fibrosis (p = 0.80 revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94, aldolase (p = 0.73, creatine

  6. Tissue Renin-Angiotensin Systems: A Unifying Hypothesis of Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Jeppe eSkov

    2014-02-01

    Full Text Available The actions of angiotensin peptides are diverse and locally acting tissue renin-angiotensin systems (RAS are present in almost all tissues of the body. An activated RAS strongly correlates to metabolic disease (e.g. diabetes and its complications and blockers of RAS have been demonstrated to prevent diabetes in humans.Hyperglycemia, obesity, hypertension, and cortisol are well-known risk factors of metabolic disease and all stimulate tissue RAS whereas glucagon-like peptide-1, vitamin D, and aerobic exercise are inhibitors of tissue RAS and to some extent can prevent metabolic disease. Furthermore, an activated tissue RAS deteriorates the same risk factors creating a system with several positive feedback pathways. The primary effector hormone of the RAS, angiotensin II, stimulates reactive oxygen species, induces tissue damage, and can be associated to most diabetic complications. Based on these observations we hypothesize that an activated tissue RAS is the principle cause of metabolic syndrome and type 2 diabetes, and additionally is mediating the majority of the metabolic complications. The involvement of positive feedback pathways may create a self-reinforcing state and explain why metabolic disease initiate and progress. The hypothesis plausibly unify the major predictors of metabolic disease and places tissue RAS regulation in the center of metabolic control.

  7. [Relationship between epicardial adipose tissue and clinical prognosis of patients with coronary heart disease after percutaneous coronary intervention].

    Science.gov (United States)

    Zhang, Y Y; Li, X; Lin, W H; Liu, J J; Jing, R; Lu, Y J; Di, C Y; Shi, H Y; Gao, P

    2018-01-16

    Objective: To further evaluate the clinical value of epicardial adipose tissue volume (EATV) in predicting the prognosis of coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: From July 2013 to July 2016 in TEDA International Cardiovascular Disease Hospital, a total of 474 patients diagnosed with CHD were included in this study.According to the result of EATV, patients were divided into three groups, group A (EATV≤75 ml), group B (75 mlEATVEATV≥150 ml). Then the level of body mass index (BMI), hypersensitive c-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested for all the three groups.All the patients were followed up for 1 year for major adverse cardiovascular events (MACE). The clinical value of EATV in predicting the occurrence of MACE events was evaluated. Results: The BMI, level of hs-CRP, TNF-α in group B were higher than group A, group C were significantly higher than group B, with statistically significant difference across all the comparisons ( P EATV was positively correlated with hs-CRP, IL-6, TNF-α ( r =0.675-0.700, P EATV level was 120.39 ml to predict MACE (area under cure: 0.751, 95% CI : 0.634-0.868, P EATV>120.39 ml can be used as an independent risk factor for predicting the occurrence of MACE. Conclusion: The level of EATV is closely related to the occurrence of MACE events, and EATV>120.39 ml is an independent risk factor for MACE in patients with CHD after PCI.

  8. Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Samantha L. Wilson

    2012-09-01

    Full Text Available Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation.

  9. Tissue engineered vascular grafts: Origins, development, and current strategies for clinical application.

    Science.gov (United States)

    Benrashid, Ehsan; McCoy, Christopher C; Youngwirth, Linda M; Kim, Jina; Manson, Roberto J; Otto, James C; Lawson, Jeffrey H

    2016-04-15

    Since the development of a dependable and durable synthetic non-autogenous vascular conduit in the mid-twentieth century, the field of vascular surgery has experienced tremendous growth. Concomitant with this growth, development in the field of bioengineering and the development of different tissue engineering techniques have expanded the armamentarium of the surgeon for treating a variety of complex cardiovascular diseases. The recent development of completely tissue engineered vascular conduits that can be implanted for clinical application is a particularly exciting development in this field. With the rapid advances in the field of tissue engineering, the great hope of the surgeon remains that this conduit will function like a true blood vessel with an intact endothelial layer, with the ability to respond to endogenous vasoactive compounds. Eventually, these engineered tissues may have the potential to supplant older organic but not truly biologic technologies, which are used currently. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

    Science.gov (United States)

    Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

    2016-03-01

    It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

  11. Pruritus in Autoimmune Connective Tissue Diseases.

    Science.gov (United States)

    Smith, Gideon P; Argobi, Yahya

    2018-07-01

    Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic

    Directory of Open Access Journals (Sweden)

    Oguzhan Sıtkı Dizdar

    2016-02-01

    Full Text Available Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002 and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient’s admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40, 46.6% (n = 29, 39.7% (n = 27, 35.3% (n = 24, 14.1% (n = 9, respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission.

  13. Celiac disease in non-clinical populations of Japan.

    Science.gov (United States)

    Fukunaga, Mai; Ishimura, Norihisa; Fukuyama, Chika; Izumi, Daisuke; Ishikawa, Nahoko; Araki, Asuka; Oka, Akihiko; Mishiro, Tomoko; Ishihara, Shunji; Maruyama, Riruke; Adachi, Kyoichi; Kinoshita, Yoshikazu

    2018-02-01

    Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease. Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests. Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings. The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms.

  14. Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yi-Wen Wang

    2017-04-01

    Full Text Available Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD. However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM, a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height2. An LTI of less than 10% of the normal value (low LTI indicates muscle wasting. Patients with low LTI (n = 40 tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.

  15. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon.

    Science.gov (United States)

    Wu, Po-Chang; Huang, Min-Nung; Kuo, Yu-Min; Hsieh, Song-Chou; Yu, Chia-Li

    2013-08-01

    Nailfold capillaroscopy is a useful tool to distinguish primary from secondary Raynaud's phenomenon (RP) by examining the morphology of nailfold capillaries but its role in disease diagnosis is not clearly established. The purpose of this study was to evaluate the roles of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases (CTDs) with RP. The data between the year 2005 and 2009 were retrieved from the nailfold capillaroscopic database of National Taiwan University Hospital (NTUH). Only the data from the patients with RP were analyzed. The criteria for interpretation of capillaroscopic findings were predefined. The final diagnoses of the patients were based on the American College of Rheumatology classification criteria for individual diseases, independent of nailfold capillaroscopic findings. The sensitivity and the specificity of each capillaroscopic pattern to the diseases were determined. The data from a total of 67 patients were qualified for the current study. We found the sensitivity and specificity of scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the specificity of the early, active, and late scleroderma patterns for SSc reached 87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for MCTD were 20%/100%. The nailfold capillaroscopic (NC) patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity. Copyright © 2012. Published by Elsevier B.V.

  16. Radiological approach to systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wiesmann, W; Schneider, M

    1988-07-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented.

  17. Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

    Science.gov (United States)

    Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

    2015-08-06

    Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

  18. New perspectives on rare connective tissue calcifying diseases.

    Science.gov (United States)

    Rashdan, Nabil A; Rutsch, Frank; Kempf, Hervé; Váradi, András; Lefthériotis, Georges; MacRae, Vicky E

    2016-06-01

    Connective tissue calcifying diseases (CTCs) are characterized by abnormal calcium deposition in connective tissues. CTCs are caused by multiple factors including chronic diseases (Type II diabetes mellitus, chronic kidney disease), the use of pharmaceuticals (e.g. warfarin, glucocorticoids) and inherited rare genetic diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification in infancy (GACI) and Keutel syndrome (KTLS). This review explores our current knowledge of these rare inherited CTCs, and highlights the most promising avenues for pharmaceutical intervention. Advancing our understanding of rare inherited forms of CTC is not only essential for the development of therapeutic strategies for patients suffering from these diseases, but also fundamental to delineating the mechanisms underpinning acquired chronic forms of CTC. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. US detection and classification of hepatic disease: Comparison of quantitative algorithms with clinical readings

    International Nuclear Information System (INIS)

    Insana, M.F.; Garra, B.S.; Shawker, T.H.; Wagner, R.F.; Bradford, M.; Russell, M.A.

    1986-01-01

    A method of quantitative digital analysis of US B-scans is used to differentiate between normal and diseased liver in vivo. The tissue signature is based on five measured parameters: four describe the tissue structure and scattering properties, the fifth is the US attenuation. The patient groups studied included 31 healthy subjects, 97 patients with chronic active hepatitis, 62 with Gaucher disease, and 10 with lymphomas. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of the quantitative method with the clinical reading of trained observers. The quantitative method showed greater diagnostic capability for detecting and classifying diffuse and some focal disease

  20. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

  1. The problem of gastroptosis as a manifestation of undifferentiated connective tissue dysplasia in the clinical practice of pediatric gastroenterologist

    Directory of Open Access Journals (Sweden)

    O.M. Shulhai

    2018-04-01

    Full Text Available In the article, the authors describe a clinical case of undifferentiated connective tissue dysplasia in 10- and 15-year-old girls. This pathology is common because it has a lot of clinical, morphological and visceral manifestations, but it is hard to diagnose. Many chronic diseases have been formed based on this pathology. Clinical cases in this article describe confirmed gastroptosis (greater curvature of the stomach is displaced downwards, below the level of the iliac crests in standing position as one of the visceral manifestations of undifferentiated connective tissue dysplasia, laboratory and instrumental findings that help to diagnose this syndrome. Gastroptosis occurs in children with asthenic type of constitution (elongated limbs, thin body, small chest, narrow shoulders, hypermobility of the joints. It comes from weak development of muscle and connective tissues so they can not endure overload, resulting is many problems, including the gastroptosis, visceroptosis etc. There are many causes of gastroptosis: congenital anomalies of the ligamentous apparatus structure, maternal disease during pregnancy, surgical intervention, sharp decrease in body weight, vitamin and proteins deficiency, irrational nutrition, lengthening the mesentery of an organ such as large intestine. If we know clinical manifestations and features of undifferentiated connective tissue dysplasia, it will allow diagnosing this pathology in a timely manner and will help more fully provide medical care to such patients, carry out their rehabilitation, psychological ada­ptation, and prevent early development of disability.

  2. Mixed connective tissue disease: The King Faisal Specialist Hospital experience

    International Nuclear Information System (INIS)

    Al-Rayes, H.; Al-Sheikh, A.; Al-Dalaan, A.; Al-Saleh, S.

    2002-01-01

    The aim of this study was to assess the clinical presentation, complications and serological analysis of mixed connective tissue disease (MCTD) at King Faisal Specialist Hospital and Research Centre (KFSHRC), and to determine the long-term clinical and immunologic outcomes. This was a retrospective study with prospective follow-up of 18 patients with MCTD who were followed at KFSHRC between 1982 and 1999. The age at onset of the disease ranged from 6 to 44 years, with mean age of 17.9 years. The female to male ratio was 2.5:1 and the mean follow-up time was 5 years. The most frequent presenting symptoms were arthralgia in all patients, Raynaud's phenomenon in 16 patients (88%) and swollen hands in 11 patients (61%). Arthritis was seen in 12 patients in (67%) and definite myositis in 10 patients (58%). The most common skin rashes encountered included lupus-like rash in 8 patients (44%) and cutaneous vasculitis in 5 patients (28%). Pulmonary hypertension occurred in 4 patients (22%). Other clinical manifestations encountered were esophageal hypomotility in 10 patients (56%), myocarditis in 2 patients (11%) and proteinurea in 2 patients (11%), while various neurological manifestations were present in 7 patients (39%). All patients exhibited higher titer of ANA and anti-nRNP antibodies. Five of the 18 patients (28%) had marked reduction in the anti-nRNP during remission. Following treatment, features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension persisted. A favorable outcome was observed in 12 patients (67%), 3 patients (17%) had continued active disease, while 3 patients (17%) died, with death related to pulmonary hypertension occurring in 2 patients (11%). The studied patients demonstrated the typical clinical and serological findings of MCTD, which support the correlation between anti-nRNP antibody specificities and MCTD. Autoantibody reactivity against nRNP polypeptides tends to regress during

  3. Radiological approach to systemic connective tissue diseases

    International Nuclear Information System (INIS)

    Wiesmann, W.; Schneider, M.

    1988-01-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented. (orig.) [de

  4. Celiac disease or positive tissue transglutaminase antibodies in patients undergoing renal biopsies.

    Science.gov (United States)

    Nurmi, Rakel; Metso, Martti; Pörsti, Ilkka; Niemelä, Onni; Huhtala, Heini; Mustonen, Jukka; Kaukinen, Katri; Mäkelä, Satu

    2018-01-01

    An association between celiac disease and renal diseases has been suggested, but the results are controversial. To investigate the prevalence of celiac disease autoimmunity among individuals undergoing renal biopsies and to evaluate whether co-existent celiac autoimmunity influences the clinical outcome of the renal disease. The prevalence of celiac autoimmunity (previous diagnosis of celiac disease or positive tissue transglutaminase antibodies) was determined in 827 consecutive patients undergoing kidney biopsies due to clinical indications. Up to 15 years' follow-up data on kidney function and co-morbidities were obtained. Celiac autoimmunity was found in 45 (5.4%) patients. Among the IgA nephropathy patients, 8.2% of had celiac autoimmunity. At the time of kidney biopsy and after a median follow-up of 5 to 6 years, renal function measured by estimated glomerular filtration rate (eGFR) was inferior in IgA nephropathy patients with celiac autoimmunity compared to those without it (P=0.048 and P=0.022, respectively). The prevalence of celiac autoimmunity seems to be high in patients undergoing renal biopsies, especially in patients with IgA nephropathy. Such autoimmunity may be associated with worse renal function in IgA nephropathy. Hence the co-existence of celiac disease should be taken into consideration when treating patients with renal diseases. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease)

    NARCIS (Netherlands)

    Karkampouna, S.; Kreulen, M.; Obdeijn, M. C.; Kloen, P.; Dorjée, A. L.; Rivellese, F.; Chojnowski, A.; Clark, I.; Kruithof-de Julio, Marianna

    2016-01-01

    Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated

  6. Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

    Science.gov (United States)

    Pandey, Manoj K; Burrow, Thomas A; Rani, Reena; Martin, Lisa J; Witte, David; Setchell, Kenneth D; Mckay, Mary A; Magnusen, Albert F; Zhang, Wujuan; Liou, Benjamin; Köhl, Jörg; Grabowski, Gregory A

    2017-03-02

    Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

  7. Histology-specific therapy for advanced soft tissue sarcoma and benign connective tissue tumors.

    Science.gov (United States)

    Silk, Ann W; Schuetze, Scott M

    2012-09-01

    Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.

  8. Tissue engineered constructs: perspectives on clinical translation.

    Science.gov (United States)

    Lu, Lichun; Arbit, Harvey M; Herrick, James L; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J

    2015-03-01

    In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

  9. Multiparametric monitoring of tissue vitality in clinical situations

    Science.gov (United States)

    Mayevsky, Avraham; Manor, Tamar; Meilin, Sigal; Razon, Nisim; Ouknine, George E.; Ornstein, Eugene

    2001-05-01

    The monitoring of various tissue's physiological and biochemical parameters is one of the tools used by the clinicians to improve diagnosis capacity. As of today, the very few devices developed for real time clinical monitoring of tissue vitality are based on a single parameter measurement. Tissue energy balance could be defined as the ratio between oxygen or energy supply and demand. In order to determine the vitality of the brain, for example, it is necessary to measure at least the following 3 parameters: Energy Demand--potassium ion homeostasis; Energy Supply-- cerebral blood flow; Energy Balance--mitochondrial NADH redox state. For other tissues one can measure various energy demand processes specific to the tested organ. We have developed a unique multiparametric monitoring system tested in various experimental and clinical applications. The multiprobe assembly (MPA) consists of a fiber optic probe for measurement of tissue blood flow and mitochondrial NADH redox state, ion selective electrodes (K+, Ca2+, H+), electrodes for electrical activities (ECoG or ECG and DC potential), temperature probe and for monitoring the brain - Intra Cranial Pressure probe (ICP). The computerized monitoring system was used in the neurological intensive care unit to monitor comatose patients for a period of 24-48 hours. Also, a simplified MPA was used in the neurosurgical operating room or during organ transplantation procedure. It was found that the MPA could be used in clinical situations and that the data collected has a significant diagnosis value for the medical team.

  10. Parvovirus B19 infection in an adult presenting with connective tissue disease-like symptoms: a report of the clinical and histological findings.

    Science.gov (United States)

    Liles, J E; Shalin, S C; White, B A; Trigg, L B; Kaley, J R

    2017-06-15

    Parvovirus B19 infections in adults are usually associated with nonspecific and mild symptoms. However, cases presenting with a lupus-like syndrome have been described, leading to the hypothesis that parvovirus infection can induce connective tissue disease. Various histopathologic features of cutaneous manifestations of parvovirus have been reported, including features which overlap with those of connective tissue disease. Herein, we discuss an unusual case of Parvovirus  B19 infection in a middle-aged woman. The biopsy results showed granulomatous vasculitis and were consistent with the previously described superantigen id reaction. This case demonstrates that infectious causes should be considered in the differential diagnosis for granulomatous vasculitis and clinicopathologic correlation is required for accurate diagnosis. We also provide a review of the literature highlighting the possible role of parvovirus in induction of a connective tissue disease-like presentation.

  11. Clinical comparison of guided tissue regeneration, with collagen membrane and bone graft, versus connective tissue graft in the treatment of gingival recessions

    Directory of Open Access Journals (Sweden)

    Haghighati F

    2006-06-01

    Full Text Available Background and Aim: Increasing patient demands for esthetic, put the root coverage procedures in particular attention. Periodontal regeneration with GTR based root coverage methods is the most common treatment used. The purpose of this study was to compare guided tissue regeneration (GTR with collagen membrane and a bone graft, with sub-epithelial connective tissue graft (SCTG, in treatment of gingival recession. Materials and Methods: In this randomized clinical trial study, eleven healthy patients with no systemic diseases who had miller’s class I or II recession defects (gingival recession  2mm were treated with SCTG or GTR using a collagen membrane and a bone graft. Clinical measurements were obtained at baseline and 6 months after surgery. These clinical measurements included recession depth (RD, recession width (RW, probing depth (PD, and clinical attachment level (CAL. Data were analyzed using independent t test with p<0.05 as the limit of significance. Results: Both treatment methods resulted in a statistically significant reduction of recession depth (SCTG=2.3mm, GTR=2.1mm; P<0.0001. CAL gain after 6 months was also improved in both groups (SCG= 2.5mm, GTR=2.1mm, compared to baseline (P<0.0001. No statistical differences were observed in RD, RW, CAL between test and control groups. Root coverage was similar in both methods (SCTG= 74.2%, GTR= 62.6%, P=0.87. Conclusion: Based on the results of this study, the two techniques are clinically comparable. Therefore the use of collagen membrane and a bovine derived xenograft may alleviate the need for connective tissue graft.

  12. Tissue-specific functional networks for prioritizing phenotype and disease genes.

    Directory of Open Access Journals (Sweden)

    Yuanfang Guan

    Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

  13. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Farini

    2014-01-01

    Full Text Available Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials.

  14. Secular trends of pregnancies in women with inflammatory connective tissue disease.

    Science.gov (United States)

    Wallenius, Marianne; Salvesen, Kjell Å; Daltveit, Anne K; Skomsvoll, Johan F

    2015-11-01

    This study examined secular trends in reproductive outcome in women with inflammatory connective tissue disease compared with reference deliveries from the general population. Historical cohort study based on data registered in the Medical Birth Register of Norway from 1967 to 2009. The study included singleton births in women recorded with connective tissue disease (n = 851) and reference deliveries from the general population (n = 2 437 110). Births were stratified in four periods, 1967-1979, 1980-1989, 1990-1999 and 2000-2009. Associations between connective tissue disease and maternal and perinatal outcomes by decade were assessed in logistic regression analyses and adjusted for maternal age at delivery and parity. In the 1970s, around 2.7 deliveries/year were registered for women with connective tissue disease (0.004% of all deliveries). This increased to 42 deliveries/year (0.07% of all deliveries) after 2000. Adjusted odds ratios (aOR) for cesarean section were 5.0 (95% CI 2.1-11.9) in the first and 1.8 (95% CI 1.4-2.3) in the last period. For preterm delivery the aOR decreased from 4.9 (95% CI 2.1-11.4) to 3.1 (95% CI 2.3-4.2) and the aOR for birthweight connective tissue disease. Adverse pregnancy outcomes were more common among women with connective tissue disease but risks have decreased over time. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  15. Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.

    Science.gov (United States)

    Vereckei, András; Fazakas, Adám; Baló, Timea; Fekete, Béla; Molnár, Mária Judit; Karádi, István

    2013-04-01

    The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case. Therefore, looking for another cause of QT(c) prolongation the possibility of chloroquine cardiotoxicity emerged, which the patient had been receiving for almost two years in supramaximal doses. Biopsy of the deltoid muscle was performed, because in chloroquine toxicity, specific lesions are present both in the skeletal muscle and in the myocardium, and electron microscopy revealed the accumulation of cytoplasmic curvilinear bodies, which are specific to antimalarial-induced myocyte damage and are absent in all other muscle diseases, except neuronal ceroid lipofuscinosis. Thus, the diagnosis of chloroquine cardiotoxicity was established. It might be advisable to supplement the periodic ophthalmological examination, which is currently the only recommendation for patients on long-term chloroquine therapy, with ECG screening.

  16. Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

    Science.gov (United States)

    von Mehren, Margaret; Randall, R Lor; Benjamin, Robert S; Boles, Sarah; Bui, Marilyn M; Ganjoo, Kristen N; George, Suzanne; Gonzalez, Ricardo J; Heslin, Martin J; Kane, John M; Keedy, Vicki; Kim, Edward; Koon, Henry; Mayerson, Joel; McCarter, Martin; McGarry, Sean V; Meyer, Christian; Morris, Zachary S; O'Donnell, Richard J; Pappo, Alberto S; Paz, I Benjamin; Petersen, Ivy A; Pfeifer, John D; Riedel, Richard F; Ruo, Bernice; Schuetze, Scott; Tap, William D; Wayne, Jeffrey D; Bergman, Mary Anne; Scavone, Jillian L

    2018-05-01

    Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations. Copyright © 2018 by the National Comprehensive Cancer Network.

  17. Identification of histological patterns in clinically affected and unaffected palm regions in dupuytren's disease.

    Directory of Open Access Journals (Sweden)

    Camilo-Andrés Alfonso-Rodríguez

    Full Text Available Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues-Dupuytren's diseased contracture cords (DDC, palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF, and normal forehand fascia (NFF. Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA, fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.

  18. Clinical manifestations and management of Gaucher disease.

    Science.gov (United States)

    Linari, Silvia; Castaman, Giancarlo

    2015-01-01

    Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

  19. Addison's disease secondary to connective tissue diseases: a report of six cases.

    Science.gov (United States)

    Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

    2009-04-01

    Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

  20. Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in inflammatory bowel disease: a pilot study.

    Science.gov (United States)

    Uchino, M; Ikeuchi, H; Bando, T; Sasaki, H; Chohno, T; Horio, Y; Takesue, Y

    2018-03-01

    Introduction Fistula formation around the ostomy site is a stoma-related complication often requiring surgical intervention. This complication may be caused by sutures or may develop as a complication of inflammatory bowel disease. Before conducting a clinical trial, we set out to investigate the safety of ostomy creation with fewer sutures using tissue adhesives in this pilot study. Methods Patients with inflammatory bowel disease who required surgery with ostomy creation at the Hyogo College of Medicine between January 2014 and December 2015 were enrolled. Safety was assessed by evaluating the incidence of stoma-related complications. Ostomy was restricted to loop ileostomy and was created with two sutures and tissue adhesives. Results A total of 14 patients were enrolled. Mean body mass index was 18.9 ± 2.0 kg/m 2 . There were no cases of ostomy retraction and no severe adverse events were observed. Conclusions This pilot study demonstrates that ostomy creation using tissue adhesives is safe. Although retraction and adverse events were not observed, even in patients with inflammatory bowel disease who generally exhibit delayed wound healing, the body mass index was extremely low in this series. This study does not strongly recommend ostomy creation with tissue adhesives; further studies are needed to clarify the efficacy and safety of the procedure.

  1. Nailfold Capillaroscopy Within and Beyond the Scope of Connective Tissue Diseases.

    Science.gov (United States)

    Lambova, Sevdalina Nikolova; Muller-Ladner, Ulf

    2018-04-20

    Nailfold capillaroscopy is a noninvasive instrumental method for morphological analysis of the nutritive capillaries in the nailfold area. In rheumatology, it is a method of choice among instrumental modalities for differential diagnosis between primary and secondary Raynaud's phenomenon (RP) in systemic rheumatic diseases. RP is a common diagnostic problem in rheumatology. Defining the proper diagnosis is a prerequisite for administration of the appropriate treatment. Thus, nailfold capillaroscopic examination is of crucial importance for the every-day practice of the rheumatologists and is currently gaining increasing attention. The most specific capillaroscopic changes are observed in Systemic Sclerosis (SSc). Due to the high prevalence of the capillaroscopic changes in this clinical entity and their early appearance, they could be used for early and very early diagnosis of the disease. More recently, "scleroderma" type capillaroscopic changes have been defined as diagnostic criterion in the new EULAR/ACR classification criteria for SSc together with the presence of scleroderma-related autoantibodies, RP, telangiectasia and other clinical signs. Capillaroscopic changes in other connective tissue diseases and in different rheumatic-like conditions like those in diabetes mellitus (e.g., diabetic stiff-hand syndrome) and paraneoplastic syndromes associated with microvascular pathology should be interpreted properly in order to obtain precise diagnosis in the shortest possible differential diagnostic process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. STANDARDISED CLINICAL EXAMINATION OF SOFT-TISSUE PAIN IN PATIENTS WITH HIP DYSPLASIA USING THE CLINICAL ENTITIES APPROACH

    DEFF Research Database (Denmark)

    Jacobsen, Julie Sandell; Hölmich, Per; Thorborg, Kristian

    2016-01-01

    Introduction In patients with symptomatic hip dysplasia soft-tissue pain may be a prevalent condition that might affect the outcome of periacetabular osteotomy (PAO). However, the distribution of soft-tissue pain in hip dysplasia has never been examined systematically using a standardised...... and reliable protocol. The aim of this study was to investigate five clinical entities in 100 patients with hip dysplasia using the clinical entities approach identifying the anatomic location of soft-tissue pain. The first 50 patients are presented in this paper. Material and Methods Fifty patients (10 males...... prevalence in the iliopsoas and the hip abductors. This indicates that patients with hip dysplasia also experience pain related to the surrounding soft-tissues, and not only from the hip joint. References (1) Holmich P, Holmich LR, Bjerg AM. Clinical examination of athletes with groin pain: an intraobserver...

  3. The Genotype-Tissue Expression (GTEx Project: Linking Clinical Data with Molecular Analysis to Advance Personalized Medicine

    Directory of Open Access Journals (Sweden)

    Judy C. Keen

    2015-02-01

    Full Text Available Evaluation of how genetic mutations or variability can directly affect phenotypic outcomes, the development of disease, or determination of a tailored treatment protocol is fundamental to advancing personalized medicine. To understand how a genotype affects gene expression and specific phenotypic traits, as well as the correlative and causative associations between such, the Genotype-Tissue Expression (GTEx Project was initiated The GTEx collection of biospecimens and associated clinical data links extensive clinical data with genotype and gene expression data to provide a wealth of data and resources to study the underlying genetics of normal physiology. These data will help inform personalized medicine through the identification of normal variation that does not contribute to disease. Additionally, these data can lead to insights into how gene variation affects pharmacodynamics and individualized responses to therapy.

  4. The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

    Science.gov (United States)

    Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

    2017-12-12

    Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

  5. Treatment of periodontal disease with guided tissue regeneration technique using a hydroxyapatite and polycaprolactone membrane

    Directory of Open Access Journals (Sweden)

    L.M.A. Martins

    Full Text Available ABSTRACT The aim of this study was to evaluate the use of a malleable membrane composed of hydroxyapatite (60% and polycaprolactone (40% as treatment of periodontal disease experimentally induced in dogs. A bone defect of standardized dimensions was created between the roots of the third and fourth premolar of 12 dogs for periodontal disease induction. Six dogs had the defect covered by the membrane and six dogs received only standard treatment for periodontal disease, also applied to dogs in the treated group. The animals were clinically monitored during the experiment. Radiographs were taken after surgery and at 60 days after treatment initiation. Clinical attachment level was also assessed in those moments. On the 60th day, dental sample of all animals, containing tooth, defect and periodontal tissues, were harvested, fixed in formalin and analyzed by microtomography and histology. During the experimental period, the animals showed no pain and purulent discharge, however, there was dehiscence in 50% of animals and membrane exposure in five out of six animals in the treated group. Clinical attachment level showed no difference between groups. Radiographs showed radiopacity equal to the alveolar bone in both groups. The microtomography revealed that the control group had higher bone volume in the defect compared to the treated group; however, the furcation was not filled by new alveolar bone in any animal. Histological analysis revealed that junctional epithelium invasion was lighter in the control group. New bone was only observed in the apical edge of the defect in both groups. Although the composite is biocompatible and able to keep the space of the defect, it did not promote periodontal tissue regeneration within 60 days of observation.

  6. A portrait of tissue phosphoprotein stability in the clinical tissue procurement process.

    Science.gov (United States)

    Espina, Virginia; Edmiston, Kirsten H; Heiby, Michael; Pierobon, Mariaelena; Sciro, Manuela; Merritt, Barbara; Banks, Stacey; Deng, Jianghong; VanMeter, Amy J; Geho, David H; Pastore, Lucia; Sennesh, Joel; Petricoin, Emanuel F; Liotta, Lance A

    2008-10-01

    Little is known about the preanalytical fluctuations of phosphoproteins during tissue procurement for molecular profiling. This information is crucial to establish guidelines for the reliable measurement of these analytes. To develop phosphoprotein profiles of tissue subjected to the trauma of excision, we measured the fidelity of 53 signal pathway phosphoproteins over time in tissue specimens procured in a community clinical practice. This information provides strategies for potential surrogate markers of stability and the design of phosphoprotein preservative/fixation solutions. Eleven different specimen collection time course experiments revealed augmentation (+/-20% from the time 0 sample) of signal pathway phosphoprotein levels as well as decreases over time independent of tissue type, post-translational modification, and protein subcellular location (tissues included breast, colon, lung, ovary, and uterus (endometrium/myometrium) and metastatic melanoma). Comparison across tissue specimens showed an >20% decrease of protein kinase B (AKT) Ser-473 (p 20% increases within 90-min postprocurement. Endothelial nitric-oxide synthase Ser-1177 did not change over the time period evaluated with breast or leiomyoma tissue. Treatment with phosphatase or kinase inhibitors alone revealed that tissue kinase pathways are active ex vivo. Combinations of kinase and phosphatase inhibitors appeared to stabilize proteins that exhibited increases in the presence of phosphatase inhibitors alone (ATF-2 Thr-71, SAPK/JNK Thr-183/Tyr-185, STAT1 Tyr-701, JAK1 Tyr-1022/1023, and PAK1/PAK2 Ser-199/204/192/197). This time course study 1) establishes the dynamic nature of specific phosphoproteins in excised tissue, 2) demonstrates augmented phosphorylation in the presence of phosphatase inhibitors, 3) shows that kinase inhibitors block the upsurge in phosphorylation of phosphoproteins, 4) provides a rational strategy for room temperature preservation of proteins, and 5) constitutes a

  7. Thrombomodulin Expression in Tissues From Dogs With Systemic Inflammatory Disease.

    Science.gov (United States)

    Kim, S D; Baker, P; DeLay, J; Wood, R D

    2016-07-01

    Thrombomodulin (TM) is a membrane glycoprotein expressed on endothelial cells, which plays a major role in the protein C anticoagulation pathway. In people with inflammation, TM expression can be down-regulated on endothelial cells and a soluble form released into circulation, resulting in increased risk of thrombosis and disseminated intravascular coagulation. TM is present in dogs; however, there has been minimal investigation of its expression in canine tissues, and the effects of inflammation on TM expression in canine tissues have not been investigated. The objective of this study was to evaluate endothelial TM expression in tissues from dogs with systemic inflammatory diseases. A retrospective evaluation of tissue samples of lung, spleen, and liver from dogs with and without systemic inflammatory diseases was performed using immunohistochemistry (IHC) and a modified manual IHC scoring system. TM expression was significantly reduced in all examined tissues in dogs diagnosed with septic peritonitis or acute pancreatitis. © The Author(s) 2016.

  8. Breast implant rupture and connective tissue disease: a review of the literature

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Lipworth, Loren; McLaughlin, Joseph K

    2007-01-01

    Large-scale epidemiologic studies to date have not found any credible association between silicone breast implants and either well-defined connective tissue diseases or undefined or atypical connective tissue diseases. It has been hypothesized that implant rupture could prompt an immunologic reac...

  9. Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

    Science.gov (United States)

    Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

    2015-01-01

    Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

  10. Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

    Science.gov (United States)

    Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

    2008-12-01

    We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

  11. Clinical presentation of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Ruocco Heloísa H.

    2006-01-01

    Full Text Available OBJECTIVE: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. METHOD: All patients were interviewed following a structured clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG repeat in the Huntington Disease gene. High resolution brain MRI was performed in all patients. RESULTS: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our Neurogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001 and reduced cerebral and cerebellum volumes (p=0.01. CONCLUSION: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were seizures and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.

  12. Clinical application for the preservation of phospho-proteins through in-situ tissue stabilization

    Directory of Open Access Journals (Sweden)

    Ding Wei

    2010-11-01

    Full Text Available Abstract Background Protein biomarkers will play a pivotal role in the future of personalized medicine for both diagnosis and treatment decision-making. While the results of several pre-clinical and small-scale clinical studies have demonstrated the value of protein biomarkers, there have been significant challenges to translating these findings into routine clinical care. Challenges to the use of protein biomarkers include inter-sample variability introduced by differences in post-collection handling and ex vivo degradation of proteins and protein modifications. Results In this report, we re-create laboratory and clinical scenarios for sample collection and test the utility of a new tissue stabilization technique in preserving proteins and protein modifications. In the laboratory setting, tissue stabilization with the Denator Stabilizor T1 resulted in a significantly higher yield of phospho-protein when compared to standard snap freeze preservation. Furthermore, in a clinical scenario, tissue stabilization at collection resulted in a higher yield of total phospho-protein, total phospho-tyrosine, pErkT202/Y204 and pAktS473 when compared to standard methods. Tissue stabilization did not have a significant effect on other post-translational modifications such as acetylation and glycosylation, which are more stable ex-vivo. Tissue stabilization did decrease total RNA quantity and quality. Conclusion Stabilization at the time of collection offers the potential to better preserve tissue protein and protein modification levels, as well as reduce the variability related to tissue processing delays that are often associated with clinical samples.

  13. Celiac disease in Saudi children. Evaluation of clinical features and diagnosis

    Directory of Open Access Journals (Sweden)

    Anjum Saeed

    2017-09-01

    Full Text Available Objectives: To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease. Methods: All children (less than 18 years with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh, Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading. Results: A total of 59 children had confirmed celiac disease. Thirty (50.8% were male. Median age was 8 years (range 1 to 16 years. The mean duration of symptoms before diagnosis was 2.3 (±1.5 years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease. Conclusion: Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

  14. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...

  15. Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases.

    Science.gov (United States)

    Pascucci, Anabella; Lynch, Peter J; Fazel, Nasim

    2016-05-01

    Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.

  16. Clinical patterns in Parkinson's disease

    NARCIS (Netherlands)

    Rooden, Stephanie Maria van

    2012-01-01

    The clinical heterogeneity of Parkinson’s disease (PD) patients may reflect the existence of subtypes of the disease. PD subtypes have often been defined by a classification according to researcher-specified criteria, such as age-at-onset or predominant clinical motor features. The general objective

  17. Whipple's disease. Report of five cases with different clinical features.

    Science.gov (United States)

    Ferrari, M de L; Vilela, E G; Faria, L C; Couto, C A; Salgado, C J; Leite, V R; Brasileiro Filho, G; Bambirra, E A; Mendes, C M; Carvalho, S de C; de Oliveira, C A; da Cunha, A S

    2001-01-01

    Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

  18. Whipple's disease. Report of five cases with different clinical features

    Directory of Open Access Journals (Sweden)

    FERRARI Maria de Lourdes de Abreu

    2001-01-01

    Full Text Available Whipple's disease (WD is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

  19. Clinical and imaging diagnosis of IgG4-related disease in the head and neck

    International Nuclear Information System (INIS)

    Yu Changliang; Liu Bin; Yu Yongqiang

    2013-01-01

    IgG4-related disease in the head and neck is a newly recognized multi-organ system disease characterized by elevated serum IgG4, infiltration of numerous IgG4-positive plasma cells, tissue fibrosis, and dramatic response to corticosteroid treatment. IgG4-related disease of the head and neck has some relative characteristics on CT and MRI, which can provide valuable information for the diagnosis and differential diagnosis, and are helpful for the clinical treatment, evaluation of therapeutic effects and prediction of prognosis. (authors)

  20. Clinical heterogeneity in Fabry disease

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    G. N. Salogub

    2015-01-01

    Full Text Available Fabry disease is an X-linked, lysosomal storage disease (OMIM: 301500, caused by α-galactosidase A deficiency, resulting in accumulation of its substrates, glycosphingolipids, primarily – globotriaosylceramide, in the lysosomes of multiple cell types with multi-system clinical manifestations, even within the same family, including abnormalities of the central and peripheral nervous system, kidneys, heart, gastrointestinal tract, lungs, organ of vision. Clinical heterogeneity is often the reason of the delayed diagnosis. Nowadays enzyme replacement therapy has proved its efficiency in the treatment of Fabry disease. Including Fabry disease in the differential diagnosis of a large range of disorders is important because of its wide clinical heterogeneity and the possibility of an earlier intervention with a beneficial treatment.

  1. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    Science.gov (United States)

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Clinical Presentation of Soft‑tissue Infections and its Management: A ...

    African Journals Online (AJOL)

    2018-03-05

    Mar 5, 2018 ... Background: Soft‑tissue infections vary widely in their nature and severity. A clear approach to the management must allow their rapid identification and treatment as they can be life‑threatening. Objective: Clinical presentation of soft‑tissue infections and its management. Materials and Methods: A ...

  3. Clinical diagnostic value of viable Schistosoma japonicum eggs detected in host tissues.

    Science.gov (United States)

    Gu, Kongzhen; Li, Yuesheng; Driguez, Patrick; Zeng, Qingren; Yu, Xinlin; Sun, Hui; Cai, Liting; He, Yongkang; Wang, Wenyang; McManus, Donald P

    2017-04-04

    Schistosomiasis, one of the neglected tropical diseases, is endemic in more than 70 countries. However, the clinical diagnosis of patients with a low degree of infection is an unsolved technical problem. In areas endemic for schistosomiasis japonica, proctoscopy detection of eggs has been one method used for clinical diagnosis. However, it is often a challenge to find typical live eggs and it is difficult to distinguish live eggs from large numbers of partially degraded and/or completely degraded eggs within colon biopsy tissue. To address this problem, we tested six different morphological and biochemical/molecular markers (ALP; morphological characteristics of egg; CalS (calcified substance); AOS (antioxidase); SDHG (succinic dehydrogenase) and SjR2 mRNA (retrotransposons 2 of S.japonicum genome mRNA)), including four new markers (CalS; AOS; SDHG and SjR2 mRNA.), to determine the viability of S. japonicum eggs deposited in human and mouse colon tissues. Our ultimate aim is to obtain a new method that is more sensitive, practical and accurate to clinically diagnose schistosomiasis. Tissue samples were collected from mice at six different time points during S. japonicum infection with or without treatment with praziquantel (PZQ). Four new biochemical or molecular markers were used for the detection of egg viability from mouse liver and intestinal samples: CalS; AOS; SDHG and SjR2 mRNA. Subsequently, all markers were employed for the detection and analysis of eggs deposited in biopsy materials from patients with suspected schistosomiasis japonica for clinical evaluation. Microscopic examination of the egg morphology, worm burden in vivo and ALP (alkaline phosphatase) levels were used as a reference standard to evaluate the sensitivity and reliability of four new markers detecting egg viability. The results of the study showed that the morphology of S. japonicum eggs deposited in tissues of hosts with schistosomiasis, especially cases with chronic schistosomiasis, is

  4. Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

    Directory of Open Access Journals (Sweden)

    K Gautam

    2015-03-01

    Full Text Available Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2 cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it difficult to take clinical decisions. Newer technologies were introduced for the antibody detection to ensure high sensitivity and specificity. This article intends to provide an overview of the concepts on ANA testing, the different diagnostic methods available, the various patterns and clinical utility, the clinical guidelines to be followed, the drawbacks and what lies ahead in the future of ANA testing.Journal of Pathology of Nepal (2015 Vol. 5, 766-773

  5. Clinical significance of abnormal nonosseous soft tissue uptake of bone tracer

    International Nuclear Information System (INIS)

    Zhu Bao; Shang Yukun; Li Jiannan; Bai Jing; Cai Liang

    2006-01-01

    Objective: To evaluate the clinical significance of abnormal soft tissue uptake of bone tracer. Methods: Thirty patients with abnormal soft tissue uptake of bone tracer on 99 Tc m -methylene diphosphonic acid (MDP) skeletal imaging were analyzed. Radioactivity of soft tissue accumulated equal to or greater than the ribs were considered as abnormal. The result was compared with pathology, MRI, CT, X-ray, ultrasound, findings for evaluating its clinical significance. Results: In 7 patients with diffuse liver uptake of 99 Tc m -MDP, 6 were massive and 1 nodular liver cancer. In 2 patients with local liver uptake, one was metastatic and the other primary liver cancer. In 5 local lung uptake cases 4 were primary lung cancer and one metastatic. In 5 cases with colonic uptake 1 was schistosomiasis while the other 4 unexplainable. Subcutaneous tissue uptake was observed in 4 patients, symmetrical uptake in 2 patients with metastatic calcification microfoci in multiple myeloma, unsymmetrical uptake in 2 patients with hemangioma and abscess. Pleural uptake in 3 patients all was metastatic cancer. Abdominal uptake in 3 patients was omentum, paravertebral soft tissue metastasis and unknown cause. Breast uptake in one patient was due to breast cancer. Conclusions: There are many causes resulting in abnormal nonosseous soft tissue uptake of 99 Tc m -MDP. The final diagnosis should correlate with clinical data and other examinations. (authors)

  6. [Nailfold capillaroscopy in the evaluation of Raynaud's phenomenon and undifferentiated connective tissue disease].

    Science.gov (United States)

    Cortes, Sara; Clemente-Coelho, Paulo

    2008-01-01

    Microvascular abnormalities involved in the pathogenic mechanism of several connective tissue disorders can be detected by nailfold capillaroscopy. Evaluation of the interest of nailfold capillaroscopy results in patients with Raynaud s phenomenon or undifferentiated connective tissue disease and their correlation with diagnostic and therapeutical evolution. Selection of capillaroscopic and laboratory results of patients with the diagnosis of Raynaud s phenomenon (without defined connective tissue disease) or undifferentiated connective tissue disease. Evaluation of the present diagnosis and treatment comparing with the ones existed at the time of capillaroscopy performance. 80 patients were enrolled with an age of 51.4+/-14.3 years (mean+/-SD) 78 females (97.5%) with Raynaud s phenomenon and undifferentiated connective tissue disease 27 patients (33.8%); Raynaud s Phenomenon 46 patients (57.5%); undifferentiated connective tissue disease 7 patients (8.7%). The capillaroscopic results were normal 30 patients (37.5%); minor changes tortuosity enlargement 16 patients (20.0%) major changes 34 patients (42.5%) hemorrhages 25 patients (31.3%) megacapillaries 26 patients (32.5%) avascular areas 3 patients (3.8%). The introduction of new treatments after the capillaroscopy occurred in 32 patients (40.0%) and a new diagnosis was done in 39 patients (48.8%). Major changes in capillaroscopy correlated with the change of diagnosis and the introduction of a new treatment (pNailfold capillaroscopy performed in patients with isolated Raynaud s phenomenon or undifferentiated connective tissue disease has a role in the prognostic evaluation related to the possibility of an evolution of the diagnosis or to the need of the introduction of new treatments.

  7. Fibrocystic disease of vulvar ectopic breast tissue. Case report and review of the literature.

    Science.gov (United States)

    Baykal, C; Tulunay, G; Usubutun, A; Küçükali, T; Ozer, S; Demir, O F

    2004-01-01

    Mammary glands located in the vulvar region have been named as ectopic breast tissue or anogenital mammary glands by different authors. Literature on pathologies of ectopic breast tissue located in the vulvar region is rare. Most of the reports are about the malignancies arising from this ectopic tissue. We report a case of fibrocystic disease of the mammary glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated during pregnancy. Ectopic breast tissue in the vulva is a rare entity and fibrocystic disease of this tissue has rarely been reported in the English literature. Copyright (c) 2004 S. Karger AG, Basel.

  8. A Histopathological Study of Pulmonary Hypertension in Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Nobuhito Sasaki

    2011-01-01

    Full Text Available Connective tissue diseases (CTD, such as systemic sclerosis (SSc, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCTD, develop pulmonary hypertension (PH. Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

  9. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  10. Selection, processing and clinical application of muscle-skeletal tissue

    International Nuclear Information System (INIS)

    Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G.

    2007-01-01

    Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

  11. Maintaining clinical tissue archives and supporting human research: challenges and solutions.

    Science.gov (United States)

    Giannini, Caterina; Oelkers, Michael M; Edwards, William D; Aubry, Marie Christine; Muncil, Maureen M; Mohamud, Koshin H; Sandleback, Sara G; Nowak, John M; Bridgeman, Andrew; Brown, Marie E; Cheville, John C

    2011-03-01

    The increasing number of requests for use of clinically archived tissue in translational research poses unique challenges. Conflicts may arise between pathologists who are responsible for overseeing and preserving the tissues and investigators who need these materials for research purposes. To evaluate the status of our institution's Tissue Registry Archive and to develop updated written policies and procedures to support a new modern and robust tracking system with features of a library loan system. An observational study was performed. We found the existing process for managing loans of tissue (slides and paraffin blocks) to be insufficient for the complexity and volume of this task. After extensive customization, a new tracking system was implemented in January 2008. Analysis of the first year of the system's use (2008) showed that of the 206,330 slides and 51,416 blocks loaned out in 2008, 92% and 94%, respectively, were returned by the due date. These rates were markedly improved from those before the new system: 61% and 47%, respectively, in 2005. Material permanently "lost" in 2008 represented only 0.02% of slides and 0.05% of blocks, none of which was the only diagnostic material for the case. With expanding needs for archived tissues for clinical care and growing demands for translational research, it is essential that pathology departments at institutions with large tissue-based research endeavors have a tracking and management system in place to meet clinical, educational, and research needs, as well as legal requirements.

  12. Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

    Directory of Open Access Journals (Sweden)

    João Tadeu Damian Souto Filho

    2011-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

  13. Celiac disease in Saudi children. Evaluation of clinical features and diagnosis.

    Science.gov (United States)

    Saeed, Anjum; Assiri, Asaad; Assiri, Hebah; Ullah, Anhar; Rashid, Mohsin

    2017-09-01

     Objectives: To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease. Methods: All children (less than 18 years) with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh,  Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading. Results: A total of 59 children had confirmed celiac disease. Thirty (50.8%) were male. Median age was 8 years (range 1 to 16 years). The mean duration of symptoms before diagnosis was 2.3 (±1.5) years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease. Conclusion: Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

  14. MINERALIZATION DISORDER OF OSSEOUS TISSUE AMONG THE CHILDREN, SUFFERING FROM INFLAMMATORY BOWEL DISEASES

    Directory of Open Access Journals (Sweden)

    E.A. Yablokova

    2006-01-01

    Full Text Available The growth rate of inflammatory bowel diseases among children actualizes early detection of this pathology form and its aftera effects, including secondary osteoporosis. The research purpose is to study the characteristics of osseous tissue mineralization, disorder of physical growth and sexual maturity of children, suffering from inflammatory bowel diseases. The researchers have examined 116 children, including 33 children, suffering from inflammatory bowel diseases; 26 children, suffering from persistent colitis; 29 children, suffering from gasatroduodenitis; and 28 children with no GI tract pathologies. The study deals with estimate of level of mineral osseous tissue density, biochemical rates of osseous metabolism, as well as physical growth and sexual maturity. reduction of mineral osseous tissue density was found among 48,5% of children, suffering from inflammatory bowel diseases, 23% of children, suffering from persistent colitis, 31% of children, suffering from chronic gastritis and 18% of almost healthy children, at the same time, it was more apparent among children, suffering from inflammatory bowel diseases. The lowest rates of mineral osseous tissue density were among girls. Calcium phosphoric metabolism did not change apart from calcium creatinine coefficient, if osteopenia was observed. Thus, reduction of mineral osseous tissue density is often observed among children, suffering from inflammatory bowel diseases, especially among adolescent girls. Therefore, it conditions the necessity to include densimetry into the conventional examination plan for children, suffering from inflammatory bowel diseases. Authors also find it advisable to monitor physical growth and sexual maturity of children.Key words: children, inflammatory bowel diseases, osteoporosis.

  15. Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma.

    Science.gov (United States)

    Keung, Emily Z; Chiang, Yi-Ju; Voss, Rachel K; Cormier, Janice N; Torres, Keila E; Hunt, Kelly K; Feig, Barry W; Roland, Christina L

    2018-01-01

    The incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies. We identified and categorized 89,870 STS patients from the National Cancer Data Base (1998-2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in 1404 patients; 1750 had clinically suspicious but not pathologically confirmed LNM (cN1). Survival analyses were performed by Kaplan-Meier method. Of 3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous distant metastasis (M1). LNM affected a small proportion of patients (5.8% head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0 disease, median overall survival (OS) was 28.2 months, varying by histology. Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma, and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1, and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0 months, p < 0.001). Despite clinical suspicion, pathologic LN evaluation in STS is inconsistently performed. LNM occurs across anatomic disease sites and is unevenly distributed across histologies. Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease. Published by Elsevier Ltd.

  16. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

    LENUS (Irish Health Repository)

    Rooney, Terence

    2012-02-01

    OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

  17. Clinical manifestations of pulmonary mucosa-associated lymphoid tissue lymphoma: single-center experience with 18 patients

    Directory of Open Access Journals (Sweden)

    Zhao S

    2018-01-01

    Full Text Available Shasha Zhao,1,2 Lin Zhang,3 Zhenyang Gu,1 Chengying Zhu,1,2 Shu Fang,1 Nan Yang,1 Feiyan Wang,1,2 Lixun Guan,1 Lan Luo,1 Chunji Gao1 1Department of Hematology, Chinese People’s Liberation Army (PLA General Hospital, Beijing, 2School of Medicine, Nankai University, Tianjin, 3Department of Hematology, First Hospital of Qinhuangdao, Qinhuangdao, China Purpose: Pulmonary mucosa-associated lymphoid tissue (MALT lymphoma is a rare entity. To date, the optimal treatment for this disease is still under debate. The aim of this study was to analyze and summarize the clinical manifestations and therapeutic experience of 18 pulmonary MALT lymphoma patients to collect information about the optimal treatment modality. Patients and methods: A retrospective analysis was performed in patients who were diagnosed with pulmonary MALT lymphoma at the Chinese People’s Liberation Army General Hospital from April 1995 to April 2016. Results: Clinical data of 18 patients were available. The median age was 55 (range, 34–67 years. Also, 61.1% of the patients were male. Only 33.3% had a history of smoking and 27.8% of the patients had tuberculosis. Treatment modalities included surgery alone in 1 patient (5.6%, chemotherapy in 10 patients (55.5%, surgery in combination with chemotherapy in 6 patients (33.3% and observation in 1 patient (5.6%. Over the median observation period of 93 months, 2 patients died, the median progression-free survival was 6 years, and the estimated 5- and 10-year overall survival rates were 94.1% and 83.7%, respectively. The survival data confirmed the indolent nature of the disease. There was no difference in progression-free survival between the chemotherapy group and the surgery in combination with chemotherapy group. Conclusion: Pulmonary MALT lymphoma tended to be an indolent disease. In order to preserve the lung function and reduce the risks associated with surgery, chemotherapy might be an optimal choice for the treatment of

  18. Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

    Science.gov (United States)

    Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

    2009-03-01

    Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

  19. Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

    Science.gov (United States)

    Kargi, Atil Y; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

  20. Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Atil Y. Kargi

    2014-01-01

    Full Text Available Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

  1. Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

    Science.gov (United States)

    Bodel, P

    1974-01-01

    The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

  2. Metallothionein expression in placental tissue in Menkes' disease

    DEFF Research Database (Denmark)

    Hærslev, T.; Krag Jacobsen, G.; Horn, N.

    1995-01-01

    . The avidin-biotin-complex (ABC)-technique was used. The copper content was measured by neutron activation analysis (NAA). In all placental tissue sections positive MT immunostaining appeared only in the trophoblast and only in proliferating cells. In placental tissue sections obtained from foetuses...... and children affected by Menkes' disease an additional MT immunostaining appeared in the Hofbauer cells of the chorionic villi. This staining was associated with an increased content of copper as measured by NAA. We conclude that the immunohistochemical demonstration of MT reflects the copper content and may...

  3. [Ovarian tissue cryopreservation in cancer patients--six years of clinical experience].

    Science.gov (United States)

    Huser, M; Záková, J; Crha, I; Smardová, L; Král, Z; Revel, A; Ventruba, P

    2012-04-01

    Presentation of clinical results and experience with this technique during past six years. Original paper. Gynekologicko-porodnická klinika LF MU a FN Brno, Interní hemato-onkologická klinika LF MU a FN Brno, Department of Obstetrics and Gynecology. Hadassah University Hospital Ein-Karem, Jerusalem, Izrael. Ovarian tissue cryopreservation (OTC) and its future auto-transplantation becomes an alternative for patients to prevent serious damage of ovarian function by oncology treatment. Patient is indicated to OTC in case of high risk of ovarian failure due to planned chemotherapy and impossibility to use other oncofertility techniques. Ovarian tissue harvesting is done by laparoscopy in short-term general anesthesia. After tissue processing the samples are cryopreserved in programmable automatic freezer or by vitrification. The auto-transplantation of ovarian tissue is planned after the complete cure of patient's malignancy. Our workplace doesn't have own experience with tissue transplantation - until now cryopreserved tissue has not yet been utilized by the patients. Clinical experience with this technique gained by our team during academic stay in abroad Israeli clinic is presented. During the years of 2005-2011 the OTC was performed in 19 cancer patients before chemotherapy. In majority of cases, patients suffered from blood or lymph node systemic malignancy (84%). Average age of women was 26 years. The patient set consisted of mostly nulliparous women (88%). Patient's average body mass index was 23,9 kg/m2. The length of systemic chemotherapy averaged 7.1 months. Time from fertility preservation counseling to chemotherapy was not exceeding one week (7.2 days on average). Ovarian tissue harvesting was conducted by laparoscopic surgery in all cases. The length of surgery did not exceed 60 minutes and no surgical complications were observed. The case of ovarian tissue transplantation performed on abroad university settings is discussed. In the consensus of with

  4. Elements determination of clinical relevance in biological tissues Dmdmdx/J dystrophic mice strains investigated by NAA

    International Nuclear Information System (INIS)

    Metairon, Sabrina

    2012-01-01

    In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD mdx /J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd mdx /J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  5. Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

    Science.gov (United States)

    Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

    2013-11-01

    Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (Preactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

  6. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Directory of Open Access Journals (Sweden)

    Eoin Neil McNamee

    2016-08-01

    Full Text Available Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues (GALT maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT, which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD, their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein we discuss the main theories of intestinal tertiary lymphoid tissue neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.

  7. The influence of Simvastatin and Korargin on the clinical course of coronary heart disease, body weight and distribution of adipose tissue in patients with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    E. A. Pogrebniak

    2013-06-01

    Full Text Available Diabetes mellitus (DM is one of the most influential risk factors for the development of cardiovascular diseases. Incidence of coronary heart diseases (CHD and acute myocardial infarction in diabetic patients is much higher than in people without diabetes. Type 2 DM affects other risk factors of CHD due to the fact that, as a rule, it is accompanied by obesity, hypertension, hypertriglyceridemia and decrease of high density lipoproteins. Purpose of the investigation – to improve the efficiency of treatment of patients with CHD with type 2 DM based on the effect of Simvastatin and Korargin on it’s clinical course, body weight and the distribution of adipose tissue. Materials and methods of the investigation. The study involved 175 patients with CHD aged from 34 to 87, mean age was 61,0 ± 8,0 years, among whom there were 96 (54,9% men and 79 (45,1% women. All surveyed received conventional treatment. Depending on supplementary prescriptions patients were divided into eight groups: 1 group - 22 patients with CHD who were prescribed Simvastatin, 2 group - 20 patients with CHD who were prescribed Korargin, 3 group - 20 patients with coronary artery disease who were prescribed simultaneously both Simvastatin and Korarhin, 4 group - 20 patients with CHD with type 2 diabetes treated with Simvastatin, 5 group - 23 patients with CHD with type 2 diabetes who took Korargin, 6 group - 27 patients with CHD with type 2 diabetes, who were prescribed both Simvastatin and Korargin in addition to conventional treatments, 7 group - 20 patients with CHD who received only conventional treatments, 8 group - 23 patients with coronary artery disease combined with type 2 diabetes who received only conventional treatments. Simvastatin ("Vazostat-Health" FC "Health", Kharkiv was administered at a daily dose of 20 mg at night during 6 months, Korargin (JSC "Engineer", Uman - 0,1 g of L-arginine hydrochloride with 0.1 g of inosine – was administered at a dose of 3

  8. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  9. Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease Location.

    Science.gov (United States)

    Aziz, Danish Abdul; Moin, Maryum; Majeed, Atif; Sadiq, Kamran; Biloo, Abdul Gaffar

    2017-01-01

    To determine different clinical presentationsand disease location demarcatedby upper and lower gastrointestinal endoscopyand relevant histopathologyin children diagnosed with inflammatory bowel disease (IBD). This is 5 years (2010 to 2015) retrospective studyconducted at the Aga Khan University Hospitalenrolling65admitted children between 6 months to 15years from either gender, diagnosed with IBD on clinical presentation, endoscopy and biopsy. Different clinical presentations at the time of diagnosis were noted in different categories of the disease. All patients underwent upper and lower (up to the terminal ileum) endoscopy with multiple punch biopsies and histologic assessment of mucosal specimens. All endoscopies were done by paediatric gastroenterologists at endoscopy suite of the hospital and all specimens were reported by the pathology department. ESPGHAN revised criteria for the diagnosis of inflammatory bowel disease in children and an adolescent was used to standardize our diagnosis. Extent of disease on endoscopy and relevant histopathology of the biopsy samples were noted at the time of diagnosis. Data was summarized using mean, standard deviation, numbers and percentages for different variables. Total 56 children were enrolled according to inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%) patients were labeled as Indeterminate colitis (IC). Mean age at onset of symptoms was10.03±2.44 and mean age at diagnosis was11.10±2.36. Abdominal pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC. Patients diagnosed with indeterminate colitis(IC) had similar clinical features as in UC patients. Only 7% patients had some extra-intestinal features in the form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 ±12.89) was relatively high in

  10. How are cancer and connective tissue diseases related to sarcoidosis?

    Science.gov (United States)

    Chopra, Amit; Judson, Marc A

    2015-09-01

    Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk).

  11. Development of tissue bank

    Directory of Open Access Journals (Sweden)

    R P Narayan

    2012-01-01

    Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  12. Adjunctive Systemic Antimicrobial Therapy vs Asepsis in Conjunction with Guided Tissue Regeneration: A Randomized, Controlled Clinical Trial.

    Science.gov (United States)

    Abu-Ta'a, Mahmoud

    2016-01-01

    This randomized clinical trial compares the usefulness of adjunctive antibiotics, while strict asepsis was followed during periodontal surgery involving guided tissue regeneration. Two groups of 20 consecutive patients each with advanced periodontal disease were randomly assigned to treatment. They displayed one angular defect each with an intrabony component ≥3 mm, probing pocket depth and probing attachment level (PAL) ≥7 mm. Test group included 13 males, mean age 60 years, treated with enamel matrix derivative (EMD) and demineralized freeze-dried bone allograft with modified papilla preservation technique, received oral amoxicillin 1 gm, 1 hour preoperatively and 2 gm for 2 days postoperatively. Control group included 10 males, mean age 57 years, treated with EMD and demineralized freeze-dried bone allograft with modified papilla preservation technique, received no antibiotics. Outcome measures were clinical attachment level (CAL) gain, residual periodontal pocket depth (res. PD), gingival recession (GR), bleeding on probing (BOP), adverse events and postoperative complications. Patients were followed up to 12 months after periodontal surgery involving guided tissue regeneration. There were no significant differences between both groups for CAL gain, res. PD, GR, BOP nor other clinical parameters, though patients' subjective perception of postoperative discomfort was significantly smaller in the group receiving antibiotics. Antibiotics do not provide significant advantages concerning clinical periodontal parameters nor concerning postoperative infections in case of proper asepsis. It does, on the contrary, reduce postoperative discomfort. Regarding the results of this study, adjunc-tive systemic antibiotics in combination with guided tissue regeneration may be useful in reducing postoperative discomfort but may not be helpful for improving periodontal regeneration outcomes.

  13. Electron probe microanalysis for clinical investigations: Microdrop and soft tissue analysis

    International Nuclear Information System (INIS)

    Ingram, M.J.; Ingram, F.D.

    1984-01-01

    The most important advantage offered by electron probe microanalysis (EPA) for clinical investigations is the ability to analyze smaller volumes of tissue than is possible with conventional techniques. The sample can be a biological soft tissue specimen, which involves subcellular localization, or a picoliter fluid droplet. In either case, the analysis can be nondestructive and permit multiple analyses for a number of elements in a given sample. The most highly developed electron microprobe analytical technique is fluid drop analysis, popularly referred to as microdrop analysis. This method provides the investigator with an analytic capability that has an accuracy of measurement often 1% or better on 20 to 30 picoliter fluid droplets. Electron microprobe techniques have been used for studies of animal hard tissue and for studies that involve insoluble inclusions. However, the development of techniques for studies of labile constituents in animal soft tissue has been much slower. It has been necessary not only to develop appropriate methods of tissue preparation, but also to establish sound techniques for tissue collection. Although there are adequate methods for collection of most types of tissue from laboratory animals, many of these methods are not suitable for human subjects. In order to provide the reader with a better understanding of the capabilities and potential for the application of electron microprobe methodology to problems in clinical medicine, the authors discuss some of their experiences with liquid droplet analysis and quantitative electrolyte distribution measurements in animal soft tissue

  14. Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.

    2004-01-01

    Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates. PMID:14695328

  15. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

    Directory of Open Access Journals (Sweden)

    Soo Jin Park

    Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

  16. Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

    Science.gov (United States)

    Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

    2012-05-01

    Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

  17. A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

    International Nuclear Information System (INIS)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P.; Naehrlich, Lutz; Harth, Sebastian; Krombach, Gabriele A.

    2013-01-01

    Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

  18. A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P. [University Hospital Giessen, Department of Pediatric Radiology, Giessen (Germany); Naehrlich, Lutz [University Hospital Giessen, Department of Pediatrics, Giessen (Germany); Harth, Sebastian; Krombach, Gabriele A. [University Hospital Giessen, Department of Radiology, Giessen (Germany)

    2013-03-15

    Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

  19. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    Science.gov (United States)

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

    Science.gov (United States)

    Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

    To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  1. Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

    Science.gov (United States)

    Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

    2014-05-06

    Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

  2. Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols

    Directory of Open Access Journals (Sweden)

    H Madry

    2014-05-01

    Full Text Available Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

  3. Infection studies with two highly pathogenic avian influenza strains (Vietnamese and Indonesian) in Pekin ducks (Anas platyrhynchos), with particular reference to clinical disease, tissue tropism and viral shedding.

    Science.gov (United States)

    Bingham, John; Green, Diane J; Lowther, Sue; Klippel, Jessica; Burggraaf, Simon; Anderson, Danielle E; Wibawa, Hendra; Hoa, Dong Manh; Long, Ngo Thanh; Vu, Pham Phong; Middleton, Deborah J; Daniels, Peter W

    2009-08-01

    Pekin ducks were infected by the mucosal route (oral, nasal, ocular) with one of two strains of Eurasian lineage H5N1 highly pathogenic avian influenza virus: A/Muscovy duck/Vietnam/453/2004 and A/duck/Indramayu/BBVW/109/2006 (from Indonesia). Ducks were killed humanely on days 1, 2, 3, 5 and 7 after challenge, or whenever morbidity was severe enough to justify euthanasia. Morbidity was recorded by observation of clinical signs and cloacal temperatures; the disease was characterized by histopathology; tissue tropism was studied by immunohistochemistry and virus titration on tissue samples; and viral shedding patterns were determined by virus isolation and titration of oral and cloacal swabs. The Vietnamese strain caused severe morbidity with fever and depression; the Indonesian strain caused only transient fever. Both viruses had a predilection for a similar range of tissue types, but the quantity of tissue antigen and tissue virus titres were considerably higher with the Vietnamese strain. The Vietnamese strain caused severe myocarditis and skeletal myositis; both strains caused non-suppurative encephalitis and a range of other inflammatory reactions of varying severity. The principal epithelial tissue infected was that of the air sacs, but antigen was not abundant. Epithelium of the turbinates, trachea and bronchi had only rare infection with virus. Virus was shed from both the oral and cloacal routes; it was first detected 24 h after challenge and persisted until day 5 after challenge. The higher prevalence of virus from swabs from ducks infected with the Vietnamese strain indicates that this strain may be more adapted to ducks than the Indonesia strain.

  4. Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

    Science.gov (United States)

    Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

    2013-08-01

    To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

  5. The diagnosis of MR and CT scan for myofascitis of connective tissue disease: comparison with biopsy examination

    International Nuclear Information System (INIS)

    Xu Jianrong; Zhou Yan; Chai Weimin; Yao Qiuying; Li Lei; Li Lan; Li Zhengyang

    2002-01-01

    Objective: To evaluate the utility of MRI, CT and biopsy examinations in detecting myofascitis lesions of connective tissue disease. Methods: The study group consisted of 22 patients proven by clinical features and laboratory examination, including 8 cases of dermatomyositis (DM), 12 cases of polymyositis (PM), and 2 cases of eosinophilic fascitis. All patients received CT scan, SE-T 1 WI, SE-T 2 WI, SPIR, and CT guiding biopsy at the thigh region. Results: Biopsy detected muscular diseases in 17 cases and fascitis in 5 cases. MRI detected muscular diseases in 14 and fascitis in 9. CT detected muscular diseases in 5 and fascitis in 9. Myositis, amyotrophy, and fascitis may be alone or united in one case. Myositis (9 cases) appeared as low signal on T 1 WI and high signal on T 2 WI or SPIR. Amyotrophy (9 cases) presented hyperintensity on both T 1 WI and T 2 WI. SPIR was more sensitive in detecting myositis than CT and T 1 WI, P < 0.05. Myositis was more frequent in cases with DM(6/8) than in cases with PM (3/12), P < 0.05. Also, myositis was more frequently encountered in active phase (7/11) than in quiescent phase (2/11). Conclusion: MRI and CT appear to be valuable in quantitatively and qualitatively estimating myofascitis of connective tissue diseases

  6. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  7. Prediction of disease-related genes based on weighted tissue-specific networks by using DNA methylation.

    Science.gov (United States)

    Li, Min; Zhang, Jiayi; Liu, Qing; Wang, Jianxin; Wu, Fang-Xiang

    2014-01-01

    Predicting disease-related genes is one of the most important tasks in bioinformatics and systems biology. With the advances in high-throughput techniques, a large number of protein-protein interactions are available, which make it possible to identify disease-related genes at the network level. However, network-based identification of disease-related genes is still a challenge as the considerable false-positives are still existed in the current available protein interaction networks (PIN). Considering the fact that the majority of genetic disorders tend to manifest only in a single or a few tissues, we constructed tissue-specific networks (TSN) by integrating PIN and tissue-specific data. We further weighed the constructed tissue-specific network (WTSN) by using DNA methylation as it plays an irreplaceable role in the development of complex diseases. A PageRank-based method was developed to identify disease-related genes from the constructed networks. To validate the effectiveness of the proposed method, we constructed PIN, weighted PIN (WPIN), TSN, WTSN for colon cancer and leukemia, respectively. The experimental results on colon cancer and leukemia show that the combination of tissue-specific data and DNA methylation can help to identify disease-related genes more accurately. Moreover, the PageRank-based method was effective to predict disease-related genes on the case studies of colon cancer and leukemia. Tissue-specific data and DNA methylation are two important factors to the study of human diseases. The same method implemented on the WTSN can achieve better results compared to those being implemented on original PIN, WPIN, or TSN. The PageRank-based method outperforms degree centrality-based method for identifying disease-related genes from WTSN.

  8. Recruitment of subjects into clinical trials for Alzheimer disease.

    Science.gov (United States)

    Knebl, Janice A; Patki, Deepti

    2010-09-01

    Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

  9. Autoimmune connective tissue diseases and vaccination

    Directory of Open Access Journals (Sweden)

    Ewa Więsik-Szewczyk

    2015-12-01

    Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  10. Knee Ligament Injury and the Clinical Application of Tissue Engineering Techniques: A Systematic Review.

    Science.gov (United States)

    Riley, Thomas C; Mafi, Reza; Mafi, Pouya; Khan, Wasim S

    2018-02-23

    The incidence of knee ligament injury is increasing and represents a significant cost to healthcare providers. Current interventions include tissue grafts, suture repair and non-surgical management. These techniques have demonstrated good patient outcomes but have been associated graft rejection, infection, long term immobilization and reduced joint function. The limitations of traditional management strategies have prompted research into tissue engineering of knee ligaments. This paper aims to evaluate whether tissue engineering of knee ligaments offers a viable alternative in the clinical management of knee ligament injuries. A search of existing literature was performed using OVID Medline, Embase, AMED, PubMed and Google Scholar, and a manual review of citations identified within these papers. Silk, polymer and extracellular matrix based scaffolds can all improve graft healing and collagen production. Fibroblasts and stem cells demonstrate compatibility with scaffolds, and have been shown to increase organized collagen production. These effects can be augmented using growth factors and extracellular matrix derivatives. Animal studies have shown tissue engineered ligaments can provide the biomechanical characteristics required for effective treatment of knee ligament injuries. There is a growing clinical demand for a tissue engineered alternative to traditional management strategies. Currently, there is limited consensus regarding material selection for use in tissue engineered ligaments. Further research is required to optimize tissue engineered ligament production before clinical application. Controlled clinical trials comparing the use of tissue engineered ligaments and traditional management in patients with knee ligament injury could determine whether they can provide a cost-effective alternative. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Science.gov (United States)

    McNamee, Eóin N.; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease. PMID:27579025

  12. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Science.gov (United States)

    McNamee, Eóin N; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn's disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.

  13. AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.

    Science.gov (United States)

    Hamrahian, Amir H; Yuen, Kevin C J; Hoffman, Andrew R

    2014-07-01

    To review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice. PubMed searches were performed to identify all of the available published data on medical management of Cushing disease. Medical therapy is usually not the first-line treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase. Medical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies.

  14. Clinical and Histologic Mimickers of Celiac Disease.

    Science.gov (United States)

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  15. Lutein, Zeaxanthin, and meso-Zeaxanthin in the Clinical Management of Eye Disease

    Directory of Open Access Journals (Sweden)

    Nicole K. Scripsema

    2015-01-01

    Full Text Available Lutein, zeaxanthin, and meso-zeaxanthin are xanthophyll carotenoids found within the retina and throughout the visual system. The retina is one of the most metabolically active tissues in the body. The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function. Subsequently, the effect of xanthophylls in the prevention and treatment of various eye diseases has been examined through epidemiological studies, animal studies, and clinical trials. This paper attempts to review the epidemiological studies and clinical trials investigating the effects of xanthophylls on the incidence and progression of various eye diseases. Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD, especially late AMD. Randomized, placebo-controlled clinical trials have demonstrated that xanthophyll supplementation increases macular pigment levels, improves visual function, and decreases the risk of progression to late AMD, especially neovascular AMD. Current publications on the preventive and therapeutic effects of lutein and zeaxanthin on cataracts, diabetic retinopathy, and retinopathy of prematurity have reported encouraging results.

  16. Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Brett Eugene Phillips

    2017-10-01

    Full Text Available Tolerogenic dendritic cell (tDC-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS, and Crohn’s disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells are, for the most part, increased in frequency in the circulation. Other than this observation, there are significant differences in the major phenotypes of the tDC. These differences may affect the outcome in efficacy of recently launched and impending phase II trials. Recent efforts to establish a catalog listing where tDC converge and diverge in phenotype and functional outcome are an important first step toward understanding core mechanisms of action and critical “musts” for tDC to be therapeutically successful. In our view, the most critical parameter to efficacy is in vivo stability of the tolerogenic activity over phenotype. As such, methods that generate tDC that can induce and stably maintain immune hyporesponsiveness to allo- or disease-specific autoantigens in the presence of powerful pro-inflammatory signals are those that will fare better in primary endpoints in phase II clinical trials (e.g., disease improvement, preservation of autoimmunity-targeted tissue, allograft survival. We propose that pre-treatment phenotypes of tDC in the absence of functional stability are of secondary value especially as such phenotypes can dramatically change following administration, especially under dynamic changes in the inflammatory state of the patient. Furthermore, understanding the outcomes of different methods of cell delivery and sites

  17. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Science.gov (United States)

    Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

    2017-01-01

    This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  18. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCT. The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6, including SLE (24.3 vs. 10.7. The areas under the receiver operating characteristic curves (ROC-AUCs of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72 and MCT (0.85 than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  19. Clinical observation of radiation urinary bladder disease

    International Nuclear Information System (INIS)

    Jin Yuke; Liu Libo; Zhang Haiying; Liang Shuo; Chen Dawei; Wu Zhenfeng; Dong Lihua; Lu Xuejun

    2004-01-01

    Objective: Clinical characteristic, diagnosis and treatment of radiation urinary bladder disease induced by radiation therapy for cancers in the pelvis were inquired into for providing diagnostic basis. Methods: Statistical analysis for the clinical cases was carried out. Results: The incidence of radiation bladder diseases induced by radiation therapy of cervix cancer are about 0.8%-2.96%, with an average of 2.14%. Radiation bladder disease is divided into acute radiation cystitis, chronic radiation cystitis and radiation vesical fistula. Chronic radiation cystitis is seen most often in the clinic and its main clinical symptom is painless macroscopic hematuria, which is again subdivided into slight and severe degrees. Diagnosis should include history of exposure to radiation, which dose exceed the dose threshold, and typical clinical characteristics. Conclusion: The characteristics, types and diagnostic basis of radiation urinary bladder disease analyzed in this study can provide the reference for drawing up diagnostic standard

  20. Precision Medicine Approaches to Diabetic Kidney Disease: Tissue as an Issue.

    Science.gov (United States)

    Gluck, Caroline; Ko, Yi-An; Susztak, Katalin

    2017-05-01

    Precision medicine approaches, that tailor medications to specific individuals has made paradigm-shifting improvements for patients with certain cancer types. Such approaches, however, have not been implemented for patients with diabetic kidney disease. Precision medicine could offer new avenues for novel diagnostic, prognostic and targeted therapeutics development. Genetic studies associated with multiscalar omics datasets from tissue and cell types of interest of well-characterized cohorts are needed to change the current paradigm. In this review, we will discuss precision medicine approaches that the nephrology community can take to analyze tissue samples to develop new therapeutics for patients with diabetic kidney disease.

  1. Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Muhammed Bora Demircelik

    2014-06-01

    Full Text Available OBJECTIVE:The aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease.METHODS:The study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing <50% in diameter, Group 2; and obstructive atherosclerosis (luminal narrowing ≥50% in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium. Epicardial adipose tissue thickness (mm was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses.RESULTS:The average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm.CONCLUSION:We showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases.

  2. Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Demircelik, Muhammed Bora; Gurel, Ozgul Malcok; Selcoki, Yusuf; Atar, Inci Asli; Eryonucu, Beyhan, E-mail: drdemircelik@yahoo.com [Turgut Ozal Univercity, Department of Cardiology, Ankara (Turkey); Bozkurt, Alper; Akin, Kayihan [Turgut Ozal Univercity, Department of Radiology, Ankara (Turkey); Yilmaz, Omer Caglar [Ankara Occupational Diseases Hospital, Department of Cardiology, Ankara (Turkey)

    2014-06-15

    Objective: the aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease. Methods: the study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing < 50% in diameter), Group 2; and obstructive atherosclerosis (luminal narrowing ≧ 50%) in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium). Epicardial adipose tissue thickness (mm) was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses. Results: the average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm. Conclusion: we showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases. (author)

  3. Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease

    International Nuclear Information System (INIS)

    Demircelik, Muhammed Bora; Gurel, Ozgul Malcok; Selcoki, Yusuf; Atar, Inci Asli; Eryonucu, Beyhan; Bozkurt, Alper; Akin, Kayihan; Yilmaz, Omer Caglar

    2014-01-01

    Objective: the aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease. Methods: the study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing < 50% in diameter), Group 2; and obstructive atherosclerosis (luminal narrowing ≧ 50%) in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium). Epicardial adipose tissue thickness (mm) was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses. Results: the average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm. Conclusion: we showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases. (author)

  4. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

    Science.gov (United States)

    Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

    2016-08-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

    Science.gov (United States)

    Huang, Brian J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2016-01-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

  6. Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

    OpenAIRE

    Kargi, Atil Y.; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unkn...

  7. Vasculitis associated with connective tissue diseases.

    Science.gov (United States)

    Cozzani, E; Gasparini, G; Papini, M; Burlando, M; Drago, F; Parodi, A

    2015-04-01

    Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

  8. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

    Science.gov (United States)

    Ravnic, Dino J; Leberfinger, Ashley N; Koduru, Srinivas V; Hospodiuk, Monika; Moncal, Kazim K; Datta, Pallab; Dey, Madhuri; Rizk, Elias; Ozbolat, Ibrahim T

    2017-07-01

    : Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

  9. Methodical aspects of radionuclide study of locomotor system in patients with systemic diseases of connective tissue with single photon emission computed tomography

    International Nuclear Information System (INIS)

    Potsibyina, V.V.; Oderyij, Je.A.

    1998-01-01

    The original technique was used to examine 427 patients aged 18-64 with systemic diseases of locomotor system connective tissue and 65 controls. In addition to clinical studies, radionuclide signs of locomotor system lesions was investigated with NUCLETRON APEX SP-6 CT unit using labeled with Tc-99m and osteotropic radiopharmaceuticals

  10. Imaging of musculoskeletal soft tissue infections

    Energy Technology Data Exchange (ETDEWEB)

    Turecki, Marcin B.; Taljanovic, Mihra S.; Holden, Dean A.; Hunter, Tim B.; Rogers, Lee F. [University of Arizona HSC, Department of Radiology, Tucson, AZ (United States); Stubbs, Alana Y. [Southern Arizona VA Health Care System, Department of Radiology, Tucson, AZ (United States); Graham, Anna R. [University of Arizona HSC, Department of Pathology, Tucson, AZ (United States)

    2010-10-15

    Prompt and appropriate imaging work-up of the various musculoskeletal soft tissue infections aids early diagnosis and treatment and decreases the risk of complications resulting from misdiagnosis or delayed diagnosis. The signs and symptoms of musculoskeletal soft tissue infections can be nonspecific, making it clinically difficult to distinguish between disease processes and the extent of disease. Magnetic resonance imaging (MRI) is the imaging modality of choice in the evaluation of soft tissue infections. Computed tomography (CT), ultrasound, radiography and nuclear medicine studies are considered ancillary. This manuscript illustrates representative images of superficial and deep soft tissue infections such as infectious cellulitis, superficial and deep fasciitis, including the necrotizing fasciitis, pyomyositis/soft tissue abscess, septic bursitis and tenosynovitis on different imaging modalities, with emphasis on MRI. Typical histopathologic findings of soft tissue infections are also presented. The imaging approach described in the manuscript is based on relevant literature and authors' personal experience and everyday practice. (orig.)

  11. Imaging of musculoskeletal soft tissue infections

    International Nuclear Information System (INIS)

    Turecki, Marcin B.; Taljanovic, Mihra S.; Holden, Dean A.; Hunter, Tim B.; Rogers, Lee F.; Stubbs, Alana Y.; Graham, Anna R.

    2010-01-01

    Prompt and appropriate imaging work-up of the various musculoskeletal soft tissue infections aids early diagnosis and treatment and decreases the risk of complications resulting from misdiagnosis or delayed diagnosis. The signs and symptoms of musculoskeletal soft tissue infections can be nonspecific, making it clinically difficult to distinguish between disease processes and the extent of disease. Magnetic resonance imaging (MRI) is the imaging modality of choice in the evaluation of soft tissue infections. Computed tomography (CT), ultrasound, radiography and nuclear medicine studies are considered ancillary. This manuscript illustrates representative images of superficial and deep soft tissue infections such as infectious cellulitis, superficial and deep fasciitis, including the necrotizing fasciitis, pyomyositis/soft tissue abscess, septic bursitis and tenosynovitis on different imaging modalities, with emphasis on MRI. Typical histopathologic findings of soft tissue infections are also presented. The imaging approach described in the manuscript is based on relevant literature and authors' personal experience and everyday practice. (orig.)

  12. IgG4-related disease -Mechanistic insights from both clinical and immunologic understanding of this condition.

    Science.gov (United States)

    Maehara, Takashi

    2017-01-01

    IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by tumescent lesions with characteristic storiform fibrosis, obliterative phlebitis and a marked lymphoplasmacytic infiltrate that includes a large number of IgG4 positive plasma cells. It's widely accepted that rituximab-mediated B cell depletion therapy is effective for this disease. Important mechanistic insights correlated with the pathogenesis of IgG4-RD have been gradually disclosed from studies of patients treated by B cell depletion. 1) IgG4-RD patients have the large clonal expansion of activated plasmablasts and CD4 + CTLs, so this disease might be antigen-driven. 2) CD4 + CTLs are the dominant population in affected tissues, on the other hands direct examination of T H1 and T H2 cells in tissues reveal that these subsets are sparse. 3) CD4 + CTLs into affected lesions secret cytotoxic, inflammatory, and pro-fibrotic cytokines, indicating reactivation by antigen in tissue sites. 4) The decline in CD4 + CTLs number by B cell depletion is associated with clinical remission of IgG4-RD patients. 5) CD4 + CXCR5 + T FH cells that express IL-4 are located outside germinal centers and specialized T FH cells that expanded dramatically in conditions with polarized class switching to IgG4. These results suggested that the disease pathogenesis might be based on orchestrating of activated plasmablasts, CD4 + CTLs, and T FH cells.

  13. Silicone breast implants and connective tissue disease

    DEFF Research Database (Denmark)

    Lipworth, Loren; Holmich, Lisbet R; McLaughlin, Joseph K

    2011-01-01

    The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known...... CTD, has been extensively studied. We have reviewed the epidemiologic literature regarding an association between cosmetic breast implants and CTDs, with particular emphasis on results drawn from the most recent investigations, many of which are large cohort studies with long-term follow-up, as well...... as on those studies that address some of the misinformation and historically widespread claims regarding an association between breast implants and CTDs. These claims have been unequivocally refuted by the remarkably consistent evidence from published studies, as well as numerous independent meta...

  14. Hydatid disease of the soft tissues of the lower limb: findings in three cases

    International Nuclear Information System (INIS)

    Martin, J.; Marco, V.; Zidan, A.; Marco, C.

    1993-01-01

    Three cases of hydatid disease are reported, all presenting as soft tissue lesions in the lower extremities. All three cases were studied with ultrasound (US), two with computed tomography (CT), and two with magnetic resonance (MR) imaging techniques. Two patients presented with multivesicular lesions which were considered diagnostic of hydatid disease. The third patient showed a lesion with a predominantly solid pattern, closely mimicking a soft-tissue neoplasm. US was not diagnostic, but MR outlined vesicular structures and a fibrous pericyst. Hydatid disease presenting in the soft tissues can therefore be diagnosed with confidence when it shows multivesicular lesions but MR may be the most useful imaging technique when a complex or solid pattern is present. (orig.)

  15. Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues

    DEFF Research Database (Denmark)

    Harboe, Theresa Larriba; Willems, Patrick; Jespersgaard, Cathrine

    2011-01-01

    Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transm......Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk...... of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin......, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14% in semen to 37% in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis...

  16. Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy.

    Science.gov (United States)

    Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I

    2012-11-01

    Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid

  17. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of 123I-IAZA

    Directory of Open Access Journals (Sweden)

    Leonard I. Wiebe

    2002-09-01

    Full Text Available Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. The presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes,or as a prognostic indicator for management of the disease (e.g. stroke. Over the past two decades, a number of hypoxia radioimaging agents have been developed and tested clinically. Of these, 18F-Fmiso and 123I-IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fmiso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumour to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetics. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. 18F-Fmiso and 123I-IAZA have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with 123I-IAZA , an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical applications.Os tecidos

  18. [Clinical Tests Testing New Therapies for Stargardt Disease].

    Science.gov (United States)

    Kousal, B; Ďuďáková, Ľ; Hlavatá, L; Lišková, P

    2016-02-01

    To provide information on currently ongoing clinical trials for Stargardt disease. We have searched the clinical trial register (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing studies. There are currently eight registered clinical trials enrolling patients with Stargardt disease; all in phase I or II aiming at four mechanisms of action: inhibition of the production of vitamin A toxic dimers, gene therapy restoring wild type transcription of the ABCA4 gene, neuroprotection preventing retinal cells from oxidative damage, and replacement of the damaged retinal pigment epithelium using stem cell therapy. The basic prerequisite for enrolment in the vast majority of clinical trials is confirmation of the clinical diagnosis by mutational analysis. The wide variety of therapies that are registered as clinical trials for Stargardt disease significantly raises the possibility that effective treatments will be available in the near future for this currently incurable condition and that molecular genetic testing should be increasingly considered. Stargardt disease, clinical trial, ABCA4, mutation.

  19. Overview of tracheal tissue engineering: clinical need drives the laboratory approach.

    Science.gov (United States)

    Ott, Lindsey M; Weatherly, Robert A; Detamore, Michael S

    2011-08-01

    Breathing is a natural function that most of us do not even think about, but for those who suffer from disease or damage of the trachea, the obstruction of breathing can mean severe restrictions to quality of life or may even be fatal. Replacement and reconstruction of the trachea is one of the most difficult procedures in otolaryngology/head and neck surgery, and also one of the most vital. Previous reviews have focused primarily on clinical perspectives or instead on engineering strategies. However, the current review endeavors to bridge this gap by evaluating engineering approaches in a practical clinical context. For example, although contemporary approaches often include in vitro bioreactor pre-culture, or sub-cutaneous in vivo conditioning, the limitations they present in terms of regulatory approval, cost, additional surgery, and/or risk of infection challenge engineers to develop the next generation of biodegradable/resorbable biomaterials that can be directly implanted in situ. Essentially, the functionality of the replacement is the most important requirement. It must be the correct shape and size, achieve an airtight fit, resist collapse as it is replaced by new tissue, and be non-immunogenic. As we look to the future, there will be no one-size-fits-all solution.

  20. Design of a visible-light spectroscopy clinical tissue oximeter.

    Science.gov (United States)

    Benaron, David A; Parachikov, Ilian H; Cheong, Wai-Fung; Friedland, Shai; Rubinsky, Boris E; Otten, David M; Liu, Frank W H; Levinson, Carl J; Murphy, Aileen L; Price, John W; Talmi, Yair; Weersing, James P; Duckworth, Joshua L; Hörchner, Uwe B; Kermit, Eben L

    2005-01-01

    We develop a clinical visible-light spectroscopy (VLS) tissue oximeter. Unlike currently approved near-infrared spectroscopy (NIRS) or pulse oximetry (SpO2%), VLS relies on locally absorbed, shallow-penetrating visible light (475 to 625 nm) for the monitoring of microvascular hemoglobin oxygen saturation (StO2%), allowing incorporation into therapeutic catheters and probes. A range of probes is developed, including noncontact wands, invasive catheters, and penetrating needles with injection ports. Data are collected from: 1. probes, standards, and reference solutions to optimize each component; 2. ex vivo hemoglobin solutions analyzed for StO2% and pO2 during deoxygenation; and 3. human subject skin and mucosal tissue surfaces. Results show that differential VLS allows extraction of features and minimization of scattering effects, in vitro VLS oximetry reproduces the expected sigmoid hemoglobin binding curve, and in vivo VLS spectroscopy of human tissue allows for real-time monitoring (e.g., gastrointestinal mucosal saturation 69+/-4%, n=804; gastrointestinal tumor saturation 45+/-23%, n=14; and p<0.0001), with reproducible values and small standard deviations (SDs) in normal tissues. FDA approved VLS systems began shipping earlier this year. We conclude that VLS is suitable for the real-time collection of spectroscopic and oximetric data from human tissues, and that a VLS oximeter has application to the monitoring of localized subsurface hemoglobin oxygen saturation in the microvascular tissue spaces of human subjects.

  1. IgG4-RELATED DISEASE. CLINICAL NOTES

    Directory of Open Access Journals (Sweden)

    Vladimir Ivanovich Vasilyev

    2013-01-01

    Full Text Available IgG4-related diseases are a new nosological entity that encompasses a few previously known diseases. IgG4-related systemic disease is diagnosed if two or more affected organs are detected. This group of diseases has two similar signs: serological (elevated serum IgG4 subclass concentrations and histological (organ and tissue infiltration from plasmo-cytes secreting IgG4, and eosinophils, and the development of fibrosclerosis and phlebitis obliterans. The paper describes two cases. In one case, a multisystemic disease was observed virtually at its onset whereas in the other this lesion was diagnosed several years after the natural course of the disease.

  2. A clinical approach to Lyme disease.

    Science.gov (United States)

    Nadelman, R B; Wormser, G P

    1990-05-01

    Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development.

  3. Clinical translation of autologous cell-based tissue engineering techniques as Class III therapeutics in China: Taking cartilage tissue engineering as an example

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-04-01

    Full Text Available Autologous cell-based tissue engineering (TE techniques have been clinically approved for approximately 4 years in China, since the first cartilage TE technique was approved for clinical use by the Zhejiang Health Bureau. TE techniques offer a promising alternative to traditional transplantation surgery, and are different from those for transplanted tissues (biologics or pharmaceutical, the clinical translational procedures are unique and multitasked, and the requirements may differ from those of the target tissues. Thus, the translational procedure is still unfamiliar to most researchers and needs further improvement. This perspectives paper describes the key guidelines and regulations involved in the current translational process, and shares our translational experiences in cartilage TE to provide an example of autologous cell-based TE translation in China. Finally, we discuss the scientific and social challenges and provide some suggestions for future improvements.

  4. Analyzing the "CareGap": assessing gaps in adherence to clinical guidelines in adult soft tissue sarcoma.

    Science.gov (United States)

    Waks, Zeev; Goldbraich, Esther; Farkash, Ariel; Torresani, Michele; Bertulli, Rossella; Restifo, Nicola; Locatelli, Paolo; Casali, Paolo; Carmeli, Boaz

    2013-01-01

    Clinical decision support systems (CDSSs) are gaining popularity as tools that assist physicians in optimizing medical care. These systems typically comply with evidence-based medicine and are designed with input from domain experts. Nonetheless, deviations from CDSS recommendations are abundant across a broad spectrum of disorders, raising the question as to why this phenomenon exists. Here, we analyze this gap in adherence to a clinical guidelines-based CDSS by examining the physician treatment decisions for 1329 adult soft tissue sarcoma patients in northern Italy using patient-specific parameters. Dubbing this analysis "CareGap", we find that deviations correlate strongly with certain disease features such as local versus metastatic clinical presentation. We also notice that deviations from the guideline-based CDSS suggestions occur more frequently for patients with shorter survival time. Such observations can direct physicians' attention to distinct patient cohorts that are prone to higher deviation levels from clinical practice guidelines. This illustrates the value of CareGap analysis in assessing quality of care for subsets of patients within a larger pathology.

  5. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

    2008-01-01

    to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

  6. Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, D.A., E-mail: d.a.bradley@surrey.ac.u [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Farquharson, M.J. [Department of Radiography, School of Community and Health Sciences, City University, London (United Kingdom); Gundogdu, O. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Al-Ebraheem, Alia [Department of Radiography, School of Community and Health Sciences, City University, London (United Kingdom); Che Ismail, Elna [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Kaabar, W., E-mail: w.kaabar@surrey.ac.u [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Bunk, O. [Paul Scherrer Institute, CH-5232 Villigen (Switzerland); Pfeiffer, F. [Paul Scherrer Institute, CH-5232 Villigen (Switzerland); Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne (Switzerland); Falkenberg, G. [Hamburger Synchrotronstrahlungslabor HASYLAB at Deutsches Elektronensynchrotron DESY, Notkestr. 85, D-22603 Hamburg (Germany); Bailey, M. [Surrey Ion Beam Centre, Advanced Technology Institute, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2010-02-15

    The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (mu-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (mu-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

  7. Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

    International Nuclear Information System (INIS)

    Bradley, D.A.; Farquharson, M.J.; Gundogdu, O.; Al-Ebraheem, Alia; Che Ismail, Elna; Kaabar, W.; Bunk, O.; Pfeiffer, F.; Falkenberg, G.; Bailey, M.

    2010-01-01

    The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (μ-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (μ-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

  8. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  9. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  10. Gastrointestinal Diagnosis of Classical Whipple Disease: Clinical, Endoscopic, and Histopathologic Features in 191 Patients

    Science.gov (United States)

    Günther, Ute; Moos, Verena; Offenmüller, Gabriel; Oelkers, Gerrit; Heise, Walther; Moter, Annette; Loddenkemper, Christoph; Schneider, Thomas

    2015-01-01

    Abstract Classic Whipple disease (CWD) is a systemic infection caused by Tropheryma whipplei. Different diagnostic tools have been developed over the last decades: periodic acid-Schiff (PAS) staining, T whipplei-specific polymerase chain reaction (PCR), and T whipplei-specific immunohistochemistry (IHC). Despite all these advances, CWD is still difficult to diagnose because of a variety of clinical symptoms and possibly a long time span between first unspecific symptoms and the full-blown clinical picture of the disease. Herein, we report an observational cohort study summarizing epidemiologic data, clinical manifestations, and diagnostic parameters of 191 patients with CWD collected at our institution. Gastrointestinal manifestations are the most characteristic symptoms of CWD affecting 76% of the cohort. Although the small bowel was macroscopically conspicuous in only 27% of cases, 173 (91%) patients presented with characteristic histological changes in small bowel biopsies (in 2 patients, these changes were only seen within the ileum). However, 18 patients displayed normal small bowel histology without typical PAS staining. In 9 of these patients, alternative test were positive from their duodenal specimens (ie, T whipplei-specific PCR and/or IHC). Thus, in 182 patients (95%) a diagnostic hint toward CWD was obtained from small bowel biopsies. Only 9 patients (5%) were diagnosed solely based on positive T whipplei-specific PCR and/or IHC of extraintestinal fluids (eg, cerebrospinal fluid, synovial fluid) or extraintestinal tissue (eg, lymph node, synovial tissue), respectively. Thus, despite efforts to diagnose CWD from alternative specimens, gastroscopy with duodenal biopsy and subsequent histological and molecular–biological examination is the most reliable diagnostic tool for CWD. PMID:25881849

  11. Bone and soft tissue ischemia

    International Nuclear Information System (INIS)

    Berquist, T.H.; Brown, M.L.; Joyce, J.W.; Johnson, K.A.

    1989-01-01

    This paper discusses clinical features and imaging techniques for ischemic necrosis, a common problem in the foot, particularly in diabetics and patients with other vascular diseases. Necrosis of bone and soft tissues will be considered separately as the underlying etiology and imaging evaluation differ considerably

  12. Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

    Science.gov (United States)

    Badawi, A M; Derbala, A S; Youssef, A M

    1999-08-01

    Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history

  13. Biomaterials in myocardial tissue engineering

    Science.gov (United States)

    Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

    2016-01-01

    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

  14. Clinical Presentation of Soft-tissue Infections and its Management: A Study of 100 Cases.

    Science.gov (United States)

    Singh, Baldev; Singh, Sukha; Khichy, Sudhir; Ghatge, Avinash

    2017-01-01

    Soft-tissue infections vary widely in their nature and severity. A clear approach to the management must allow their rapid identification and treatment as they can be life-threatening. Clinical presentation of soft-tissue infections and its management. A prospective study based on 100 patients presenting with soft-tissue infections was done. All the cases of soft-tissue infections were considered irrespective of age, sex, etiological factors, or systemic disorders. The findings were evaluated regarding the pattern of soft-tissue infections in relation to age and sex, clinical presentation, complications, duration of hospital stay, management, and mortality. The most commonly involved age group was in the range of 41-60 years with male predominance. Abscess formation (45%) was the most common clinical presentation. Type 2 diabetes mellitus was the most common associated comorbid condition. Staphylococcus aureus was the most common culture isolate obtained. The most common complication seen was renal failure. Patients with surgical site infections had maximum duration of stay in the hospital. About 94% of the cases of soft-tissue infections were managed surgically. Mortality was mostly encountered in the cases of complications of cellulitis. Skin and soft-tissue infections are among the most common infections encountered by the emergency physicians. Ignorance, reluctance to treatment, economic constraints, and illiteracy delay the early detection and the initiation of proper treatment. Adequate and timely surgical intervention in most of the cases is of utmost importance to prevent the complications and reduce the mortality.

  15. Clinical Observation of Concomitant Congenital Heart Disease and Anomaly of the Urinary System in Adolescent

    Directory of Open Access Journals (Sweden)

    M.P. Limarenko

    2014-08-01

    Full Text Available The article presents the clinical observation of multiple malformations in a child: combination of congenital heart disease with an anomaly of the urinary system on the background of undifferentiated connective tissue dysplasia syndrome of maximum severity. This case report is of interest to pediatricians. Children with defects of the heart and urinary system often have other malformations, so in these patients it is important to conduct a full multisystem examination.

  16. MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays.

    Science.gov (United States)

    Powers, Thomas W; Neely, Benjamin A; Shao, Yuan; Tang, Huiyuan; Troyer, Dean A; Mehta, Anand S; Haab, Brian B; Drake, Richard R

    2014-01-01

    A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues. Formalin-fixed tissues from normal mouse kidney, human pancreatic and prostate cancers, and a human hepatocellular carcinoma tissue microarray were processed by antigen retrieval followed by on-tissue digestion with peptide N-glycosidase F. The released N-glycans were detected by MALDI-IMS analysis, and the structural composition of a subset of glycans could be verified directly by on-tissue collision-induced fragmentation. Other structural assignments were confirmed by off-tissue permethylation analysis combined with multiple database comparisons. Imaging of mouse kidney tissue sections demonstrates specific tissue distributions of major cellular N-linked glycoforms in the cortex and medulla. Differential tissue distribution of N-linked glycoforms was also observed in the other tissue types. The efficacy of using MALDI-IMS glycan profiling to distinguish tumor from non-tumor tissues in a tumor microarray format is also demonstrated. This MALDI-IMS workflow has the potential to be applied to any FFPE tissue block or tissue microarray to enable higher throughput analysis of the global changes in N-glycosylation associated with cancers.

  17. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  18. Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

    Science.gov (United States)

    Versteegden, Luuk R M; de Jonge, Paul K J D; IntHout, Joanna; van Kuppevelt, Toin H; Oosterwijk, Egbert; Feitz, Wout F J; de Vries, Rob B M; Daamen, Willeke F

    2017-10-01

    Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study

  19. Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies

    NARCIS (Netherlands)

    Versteegden, L.R.; Jonge, P. de; Hout, J. in't; Kuppevelt, T.H. van; Oosterwijk, E.; Feitz, W.F.J.; Vries, R.B.M. de; Daamen, W.F.

    2017-01-01

    CONTEXT: Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. OBJECTIVE: To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order

  20. Diagnosis of Protein Losing Enteropathy in connective Tissue Diseases with 99mTc-human Serum Albumin(Hsa)

    International Nuclear Information System (INIS)

    Won, Kyoung Sook; Oh, Yeong Seok; Bang, Shin Ho; Park, Won

    1993-01-01

    Anterior abdominal scintigraphy after intravenous injection of 99m Tc-human serum albumin ( 99m Tc-HSA 20 mCi) was done in 16 patients with connective tissue diseases and 15 healthy control patients. Patients with proteinuria or hepatopathy were excluded. 1) 7(44%) patients among 16 connective tissue disease patients without the apparent evidence of external protein loss showed abnormal intestinal accumulation of albumin. 6 patients with positive albumin scintigraphy showed hypoalbuminaemia. 2) There was no false positive scintigraphic finding in control group. 3) The serum albumin level in connective tissue disease patients (3.1 ± 0.6 g/dl, n=16) was lower than control patients(3.9 ± 0.3 g/dl, n=15) (p 99m Tc-HSA scan(2.8 ± 0.6 g/dl, n=7) than the connective tissue disease patients with negative scan(3.3 ± 0.3 g/dl, n=9) (p 99m Tc-HSA scan also must be validated by more extended study and comparison with the quantitative study such as stool α -1 antitrypsin measurement. There must be a reevaluation of PLE in various diseases especially in connective tissue diseases with easy, fast, economical, and noninvasive method.

  1. Differentiation of diffuse liver disease with computer-aided tissue echo quantification

    International Nuclear Information System (INIS)

    Cha, Joo Hee; Choi, Byung Ihm; Yun, Eun Joo; Ko, Young Hwan; Song, Chi Sung; Kim, Seung Hyup; Han, Joon Koo; Kim, Tae Kyoung; Lee, Dong Hyuk; Kim, Jong Hyo

    1999-01-01

    The purpose of this study was to evaluate the efficacy of computer-aided tissue echo quantification technique in the differentiation of diffuse liver diseases. Sixty-five patients with chronic liver disease including chronic hepatitis in 21 patients, fatty liver in 11, and liver cirrhosis in 33, and 55 normal volunteers were included in this study. The sonographic images by the Sono-PACS(MARO, Seoul) was recalled and the analysis was done for the hepatic parenchymal coarseness by the program using Visual C++. Difference histogram variation (DHV), edge density (ED) and intertia of concurrence matrix (ICM) were used as the coarseness index. These three indexes were statistically significant (p<0.05) in the differentiation of these four groups. The accuracy of the differentiation between any two of four groups was 83.0%. The accuracy of the differentiation of these four groups was 70.8% at the same time. The computer-aided tissue echo quantification technique is a complementary study for the differentiation of diffuse liver disease.

  2. The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue.

    Science.gov (United States)

    Caine, Sally; Heraud, Philip; Tobin, Mark J; McNaughton, Donald; Bernard, Claude C A

    2012-02-15

    In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Tissue tropism, pathology and pathogenesis of enterovirus infection.

    Science.gov (United States)

    Muehlenbachs, Atis; Bhatnagar, Julu; Zaki, Sherif R

    2015-01-01

    Enteroviruses are very common and cause infections with a diverse array of clinical features. Enteroviruses are most frequently considered by practising pathologists in cases of aseptic meningitis, encephalitis, myocarditis and disseminated infections in neonates and infants. Congenital infections have been reported and transplacental transmission is thought to occur. Although skin biopsies during hand, foot and mouth disease are infrequently obtained, characteristic dermatopathological findings can be seen. Enteroviruses have been implicated in lower respiratory tract infections. This review highlights histopathological features of enterovirus infection and discusses diagnostic modalities for formalin-fixed paraffin-embedded tissues and their associated pitfalls. Immunohistochemistry can detect enterovirus antigen within cells of affected tissues; however, assays can be non-specific and detect other viruses. Molecular methods are increasingly relied upon but, due to the high frequency of asymptomatic enteroviral infections, clinical-pathological correlation is needed to determine significance. Of note, diagnostic assays on central nervous system or cardiac tissues from immunocompetent patients with prolonged disease courses are most often negative. Histopathological, immunohistochemical and molecular studies performed on clinical specimens also provide insight into enteroviral tissue tropism and pathogenesis. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  4. Clinical predictors of adverse course of nonspecific bacterial vulvovaginitis at girls born from mothers with dysplasia of connective tissue

    Directory of Open Access Journals (Sweden)

    Mozes V.G.

    2012-06-01

    Full Text Available Research objective: To define clinical predictors of adverse course of nonspecific bacterial vulvovaginitis (NBV at girls born from mothers with the undifferentiated forms of dysplasia of connective tissue (UFDCT. Materials: At 157 girls clinical research, bacteriological and bacterioscopy research of leucorrhoea from vagina has been conducted, NBV has been diagnosed at 111 girls. At all girls and at their mothers the immunity has been investigated; at all mothers of girls with NBV phenotypic reveals of UFDCT have been found out. Results: At girls with NBV born from mothers with UFDCT severe course of a disease has been marked; and at mothers with UFDCT and at their children with NBV disorders of humoral immunity have been revealed. Presence of more than 5 stigmas of dysembryogenesis with prevalence of thoracodiaphragmatic, articular, cosmetic syndromes and pathology of organs of vision at mothers of girls with NBV is possible to use as predictors of adverse course of the disease

  5. Clinical presentation of soft-tissue infections and its management: A study of 100 cases

    Directory of Open Access Journals (Sweden)

    Baldev Singh

    2017-01-01

    Full Text Available Background: Soft-tissue infections vary widely in their nature and severity. A clear approach to the management must allow their rapid identification and treatment as they can be life-threatening. Objective: Clinical presentation of soft-tissue infections and its management. Materials and Methods: A prospective study based on 100 patients presenting with soft-tissue infections was done. All the cases of soft-tissue infections were considered irrespective of age, sex, etiological factors, or systemic disorders. The findings were evaluated regarding the pattern of soft-tissue infections in relation to age and sex, clinical presentation, complications, duration of hospital stay, management, and mortality. Results: The most commonly involved age group was in the range of 41–60 years with male predominance. Abscess formation (45% was the most common clinical presentation. Type 2 diabetes mellitus was the most common associated comorbid condition. Staphylococcus aureus was the most common culture isolate obtained. The most common complication seen was renal failure. Patients with surgical site infections had maximum duration of stay in the hospital. About 94% of the cases of soft-tissue infections were managed surgically. Mortality was mostly encountered in the cases of complications of cellulitis. Conclusion: Skin and soft-tissue infections are among the most common infections encountered by the emergency physicians. Ignorance, reluctance to treatment, economic constraints, and illiteracy delay the early detection and the initiation of proper treatment. Adequate and timely surgical intervention in most of the cases is of utmost importance to prevent the complications and reduce the mortality.

  6. Clinical pathology observation on orbit IgG4 related disease

    Directory of Open Access Journals (Sweden)

    Ji-Hua Guo

    2015-09-01

    Full Text Available AIM:To discuss clinical pathological features of orbit IgG4 related disease(IgG4-RD. METHODS: The clinical pathological materials of 23 patients(35 eyeswith orbit IgG4-RD were collected. They were observed in terms of histology and immunohistochemistry, and its clinical and pathologic characteristics were summarized. RESULTS: There were 23 patients(35 eyeswith orbit IgG4-RD(8 male patients, 9 eyes; 15 female patients, 26 eyes, with an average age of 52.1 year-old(from age 28 to 72. 19 patients(30 eyesoccured in lacrimal gland and 4 cases(5 eyesin other places, and they went to hospital for lacrimal gland cyst or exophthalmos. There were 11 cases in one side and 12 cases in both sides. The disease lasted from 1mo to 10a, averaging 27mo. It recureded in one patient(1 eyeafter 1mo. In general inspection: Gray nodular goiter, thin fibrous coat wrapping around the lacrimal gland could be observed. Histologic characteristics: lacrimal gland bubble and catheter group shrinked or even disappeared, substituted by lymphocyte, plasma cells and lymphoid follicle and accompanied with fibrosis. Immunohistochemical staining: IgG4 positive plasma cells of 23 cases(35 eyeswas >50/HPF, and IgG4/IgG ratio of positive plasma cells was >40%. CONCLUSION: Orbit IgG4-RD mainly occures in lacrimal gland tissue, and expression of IgG4 can be detected through histologic characteristics and immunohistochemical staining. IgG4-RD should be screened, prevented and treated in the early phase.

  7. Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2007-01-01

    In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

  8. Clinical presentation of adult coeliac disease.

    LENUS (Irish Health Repository)

    Tajuddin, T

    2012-02-01

    The mode of presentation of coeliac disease has been changing to more atypical or silent disease. Few studies described the clinical presentation of adult coeliac disease in Ireland in recent years. We retrospectively collected the clinical data for all patients who had a diagnosis of coeliac disease made in our centre between January 07 and December 08. Forty seven adults, predominantly females (n = 30), had a confirmed diagnosis of coeliac disease made during the study period. In our patient cohort, the presenting symptom was diarrhoea in 19 (40%) patients, while 16 patients (34%) did not have any G.I. symptoms, 10 (21%) presented with anaemia. Females presented at a significantly younger age compared to males, with median ages at diagnosis of 44.5 and 57 years, respectively (p = 0.04). Females also presented more commonly with non G.I. symptoms (p = 0.07). The reasons behind this gender difference need further study.

  9. Dopaminreceptorscintigraphy in Parkinson's disease - Clinical correlation

    International Nuclear Information System (INIS)

    Riklund Aahlstroem, K.E.; Hietala, S.-O.; Johansson, F.

    2002-01-01

    Parkinson's disease is a severe, progressive neuro degenerative disorder which is characterised by a degeneration of the dopamine containing cells and loss of dopamine transporters (DA) in substantia nigra. Earlier 123 I-β-CIT SPECT studies have demonstrated this loss of DA content in Parkinson's disease. Recently a new radioligand 123 I-FP-CIT, with faster kinetics than b-CIT became available for imaging of the DA transporter. The applicability of this radioligand was tested in a large clinical material with early and advanced Parkinson's disease using a one day protocol. 123 I-FP-CIT uptake was decreased in patients with Parkinson's disease and this was seen three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. It appeared that 123 I-FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and other movement disorders. The scintigraphic observations were correlated to clinical findings. The results will be presented and discussed

  10. Barriers to the clinical translation of orthopedic tissue engineering.

    Science.gov (United States)

    Evans, Christopher H

    2011-12-01

    Tissue engineering and regenerative medicine have been the subject of increasingly intensive research for over 20 years, and there is concern in some quarters over the lack of clinically useful products despite the large sums of money invested. This review provides one perspective on orthopedic applications from a biologist working in academia. It is suggested that the delay in clinical application is not atypical of new, biologically based technologies. Some barriers to progress are acknowledged and discussed, but it is also noted that preclinical studies have identified several promising types of cells, scaffolds, and morphogenetic signals, which, although not optimal, are worth advancing toward human trials to establish a bridgehead in the clinic. Although this transitional technology will be replaced by more sophisticated, subsequent systems, it will perform valuable pioneering functions and facilitate the clinical development of the field. Some strategies for achieving this are suggested. © Mary Ann Liebert, Inc.

  11. [Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.

    Science.gov (United States)

    Paltsev, M A; Zuev, V A; Kozhevnikova, E O; Linkova, N S; Kvetnaia, T V; Polyakova, V O; Kvetnoy, I M

    2017-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аβ42 in CSF in case of AD, but CSF taking may have a number of side effects. Less traumatic taking of sampling tissues for the diagnosis of AD is in use of epithelium biopsy and blood portion. An increase in the expression of the hyper phosphorylated form of τ-protein is shown in blood lymphocytes of AD patients. An increase in the content of high molecular weight forms of phosphorylated t-protein and amyloid precursor protein-APP was also revealed in blood platelets of AD patients. Changes in the amount of 2 miRNA families - miR-132 family and miR-134 family were revealed in blood cells 1-5 years before the manifestation of clinical signs of AD. An increase in the concentration of bound calcium, synthesis of peptides Aβ40 and Aβ42, τ protein was observed in AD skin fibroblasts. In the olfactory and buccal epithelium an increase in the expression of hyper phosphorylated form of τ-protein and Aβ peptide was detected in patients with AD. Verification of AD markers in peripheral tissues for biopsy have the important significant for life diagnostics, prevention and and target AD treatment.

  12. Lyme disease: clinical diagnosis and treatment

    Science.gov (United States)

    Hatchette, TF; Davis, I; Johnston, BL

    2014-01-01

    Background Lyme disease is an emerging zoonotic infection in Canada. As the Ixodes tick expands its range, more Canadians will be exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease. Objective To review the clinical diagnosis and treatment of Lyme disease for front-line clinicians. Methods A literature search using PubMed and restricted to articles published in English between 1977 and 2014. Results Individuals in Lyme-endemic areas are at greatest risk, but not all tick bites transmit Lyme disease. The diagnosis is predominantly clinical. Patients with Lyme disease may present with early disease that is characterized by a “bull’s eye rash”, fever and myalgias or with early disseminated disease that can manifest with arthralgias, cardiac conduction abnormalities or neurologic symptoms. Late Lyme disease in North America typically manifests with oligoarticular arthritis but can present with a subacute encephalopathy. Antibiotic treatment is effective against Lyme disease and works best when given early in the infection. Prophylaxis with doxycyline may be indicated in certain circumstances. While a minority of patients may have persistent symptoms, evidence does not demonstrate that prolonged courses of antibiotics improve outcome. Conclusion Clinicians need to be aware of the signs and symptoms of Lyme disease. Knowing the regions where Borrelia infection is endemic in North America is important for recognizing patients at risk and informing the need for treatment. PMID:29769842

  13. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  14. Patterns of clinical presentation of adult coeliac disease in a rural setting

    Directory of Open Access Journals (Sweden)

    D'Souza Charles

    2006-09-01

    Full Text Available Abstract Background In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. Aim The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. Methods This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. Results Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. Conclusion Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority

  15. Clinical pilot study for the automatic segmentation and recognition of abdominal adipose tissue compartments from MRI data

    Energy Technology Data Exchange (ETDEWEB)

    Noel, P.B.; Bauer, J.S.; Ganter, C.; Markus, C.; Rummeny, E.J.; Engels, H.P. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Inst. fuer Radiologie; Hauner, H. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Else Kroener-Fresenius-Center for Nutritional Medicine

    2012-06-15

    Purpose: In the diagnosis and risk assessment of obesity, both the amount and distribution of adipose tissue compartments are critical factors. We present a hybrid method for the quantitative measurement of human body fat compartments. Materials and Methods: MRI imaging was performed on a 1.5 T scanner. In a pre-processing step, the images were corrected for bias field inhomogeneity. For segmentation and recognition a hybrid algorithm was developed to automatically differentiate between different adipose tissue compartments. The presented algorithm is designed with a combination of shape and intensity-based techniques. To incorporate the presented algorithm into the clinical routine, we developed a graphical user interface. Results from our methods were compared with the known volume of an adipose tissue phantom. To evaluate our method, we analyzed 40 clinical MRI scans of the abdominal region. Results: Relatively low segmentation errors were found for subcutaneous adipose tissue (3.56 %) and visceral adipose tissue (0.29 %) in phantom studies. The clinical results indicated high correlations between the distribution of adipose tissue compartments and obesity. Conclusion: We present an approach that rapidly identifies and quantifies adipose tissue depots of interest. With this method examination and analysis can be performed in a clinically feasible timeframe. (orig.)

  16. Clinical pilot study for the automatic segmentation and recognition of abdominal adipose tissue compartments from MRI data

    International Nuclear Information System (INIS)

    Noel, P.B.; Bauer, J.S.; Ganter, C.; Markus, C.; Rummeny, E.J.; Engels, H.P.; Hauner, H.

    2012-01-01

    Purpose: In the diagnosis and risk assessment of obesity, both the amount and distribution of adipose tissue compartments are critical factors. We present a hybrid method for the quantitative measurement of human body fat compartments. Materials and Methods: MRI imaging was performed on a 1.5 T scanner. In a pre-processing step, the images were corrected for bias field inhomogeneity. For segmentation and recognition a hybrid algorithm was developed to automatically differentiate between different adipose tissue compartments. The presented algorithm is designed with a combination of shape and intensity-based techniques. To incorporate the presented algorithm into the clinical routine, we developed a graphical user interface. Results from our methods were compared with the known volume of an adipose tissue phantom. To evaluate our method, we analyzed 40 clinical MRI scans of the abdominal region. Results: Relatively low segmentation errors were found for subcutaneous adipose tissue (3.56 %) and visceral adipose tissue (0.29 %) in phantom studies. The clinical results indicated high correlations between the distribution of adipose tissue compartments and obesity. Conclusion: We present an approach that rapidly identifies and quantifies adipose tissue depots of interest. With this method examination and analysis can be performed in a clinically feasible timeframe. (orig.)

  17. The Role of Tissue-Resident Donor T Cells in Rejection of Clinical Face Transplants

    Science.gov (United States)

    2017-10-01

    cells contribute to VCA rejection, and that pathogenic T cells (both donor and recipient-derived) are detectable in blood during rejection to serve as...AWARD NUMBER: W81XWH-16-1-0760 TITLE: The role of tissue-resident donor T cells in rejection of clinical face transplants PRINCIPAL...AND SUBTITLE The role of tissue-resident donor T cells in rejection of clinical face transplants 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1

  18. Non-invasive detection of periodontal disease using diffuse reflectance spectroscopy: a clinical study

    Science.gov (United States)

    Prasanth, Chandra Sekhar; Betsy, Joseph; Subhash, Narayanan; Jayanthi, Jayaraj L.; Prasanthila, Janam

    2012-03-01

    In clinical diagnostic procedures, gingival inflammation is considered as the initial stage of periodontal breakdown. This is often detected clinically by bleeding on probing as it is an objective measure of inflammation. Since conventional diagnostic procedures have several inherent drawbacks, development of novel non-invasive diagnostic techniques assumes significance. This clinical study was carried out in 15 healthy volunteers and 25 patients to demonstrate the applicability of diffuse reflectance (DR) spectroscopy for quantification and discrimination of various stages of inflammatory conditions in periodontal disease. The DR spectra of diseased lesions recorded using a point monitoring system consisting of a tungsten halogen lamp and a fiber-optic spectrometer showed oxygenated hemoglobin absorption dips at 545 and 575 nm. Mean DR spectra on normalization shows marked differences between healthy and different stages of gingival inflammation. Among the various DR intensity ratios investigated, involving oxy Hb absorption peaks, the R620/R575 ratio was found to be a good parameter of gingival inflammation. In order to screen the entire diseased area and its surroundings instantaneously, DR images were recorded with an EMCCD camera at 620 and 575 nm. We have observed that using the DR image intensity ratio R620/R575 mild inflammatory tissues could be discriminated from healthy with a sensitivity of 92% and specificity of 93%, and from moderate with a sensitivity of 83% and specificity of 96%. The sensitivity and specificity obtained between moderate and severe inflammation are 82% and 76% respectively.

  19. [Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice].

    Science.gov (United States)

    León-Pedroza, José Israel; González-Tapia, Luis Alonso; del Olmo-Gil, Esteban; Castellanos-Rodríguez, Diana; Escobedo, Galileo; González-Chávez, Antonio

    2015-01-01

    Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage-associated molecular patterns in each patient. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  20. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

    Science.gov (United States)

    Mastropasqua, Rodolfo; Agnifili, Luca; Fasanella, Vincenzo; Nubile, Mario; Gnama, Agbeanda A; Falconio, Gennaro; Perri, Paolo; Di Staso, Silvio; Mariotti, Cesare

    2017-08-01

    Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

  1. Disease related tissue damage and subsequent changes in fillet structure

    DEFF Research Database (Denmark)

    of the fish and subsequent a reduction in price. Despite this, the impact of infectious diseases on the meat quality and the mechanisms behind are poorly investigated. Wound repair is a dynamic, interactive response to tissue injury that involves a complex interaction and cross talk of various cell types......, extracellular matrix molecules, soluble mediators and cytokines. In order to describe the molecular mechanisms and processes of wound repair, a panel of genes covering immunological factors and tissue regeneration were used to measure changes at the mRNA level following mechanical tissue damage in rainbow trout...... (Oncorhynchus mykiss). Needle disrupted muscle tissue was sampled at different time points and subject to real-time RT-PCR for measuring the expression of the genes IL-1β, IL-8, IL-10, TGF-β, Myostatin-1ab, MMP-2, CTGF, Collagen-1α, VEGF, iNOS, Arg-2 and FGF. The results showed an initial phase with up...

  2. Differential Diagnoses of Overgrowth Syndromes: The Most Important Clinical and Radiological Disease Manifestations

    International Nuclear Information System (INIS)

    Lacerda, L.S.; Alves, U.D.; Zanier, J.F.C.; Machado, D.C.; Camilo, G.B.; Machado, D.C.; Camilo, G.B.; Lopes, A.J.

    2014-01-01

    Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Some of these syndromes may be associated with dysfunction in the receptor tyrosine kinase (RTK)/PI3K/AKT pathway, which results in an increased expression of the insulin receptor. In the current review, four overgrowth syndromes were characterized (Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Made lung’s disease, and neurofibromatosis type I) and illustrated using cases from our institution. Because these syndromes have overlapping clinical manifestations and have no established genetic tests for their diagnosis, radiological methods are important contributors to the diagnosis of many of these syndromes. The correlation of genetic discoveries and molecular pathways that may contribute to the phenotypic expression is also of interest, as this may lead to potential therapeutic interventions

  3. Quality management and accreditation of research tissue banks: experience of the National Center for Tumor Diseases (NCT) Heidelberg.

    Science.gov (United States)

    Herpel, Esther; Röcken, Christoph; Manke, Heike; Schirmacher, Peter; Flechtenmacher, Christa

    2010-12-01

    Tissue banks are key resource and technology platforms in biomedical research that address the molecular pathogenesis of diseases as well as disease prevention, diagnosis, and treatment. Due to the central role of tissue banks in standardized collection, storage, and distribution of human tissues and their derivatives, quality management and its external assessment is becoming increasingly relevant for the maintenance, acceptance, and funding of tissue banks. Little experience exists regarding formalized external evaluation of tissue banks, especially regarding certification and accreditation. Based on the accreditation of the National Center of Tumor Diseases (NCT) tissue bank in Heidelberg (Germany), criteria, requirements, processes, and implications were compiled and evaluated. Accreditation formally approved professional competence and performance of the tissue bank in all steps involved in tissue collection, storage, handling as well as macroscopic and histologic examination and final (exit) examination of the tissue and transfer supervised by board-certified competent histopathologists. Thereby, accreditation provides a comprehensive measure to evaluate and document the quality standard of tissue research banks and may play a significant role in the future assessment of tissue banks. Furthermore, accreditation may support harmonization and standardization of tissue banking for biomedical research purposes.

  4. Calcium pyrophosphate deposition disease: clinical manifestations

    Directory of Open Access Journals (Sweden)

    M.A. Cimmino

    2012-01-01

    Full Text Available Calcium pyrophosphate deposition (CPPD disease is an arthropathy caused by calcium pyrophosphate dihydrate (CPP crystal deposits in articular tissues, most commonly fibrocartilage and hyaline cartilage. According to EULAR, four different clinical presentations can be observed: 1 asymptomatic CPPD; 2 osteoarthritis (OA with CPPD; 3 acute CPP crystal arthritis; 4 chronic CPP inflammatory crystal arthritis. Acute CPP crystal arthritis is characterized by sudden onset of pain, swelling and tenderness with overlying erythema, usually in a large joint, most often the knee, wrist, shoulder, and hip. Occasionally, ligaments, tendons, bursae, bone and the spine can be involved. CPPD of the atlanto-occipital joint (crowned dens syndrome can cause periodic acute cervico-occipital pain with fever, neck stiffness and laboratory inflammatory syndrome. Chronic inflammatory arthritis is characterized by joint swelling, morning stiffness, pain, and high ESR and CRP. The relationship between OA and CPPD is still unclear. The main problem is whether such crystals are directly involved in the pathogenesis of OA or if they are the result of joint degeneration. Diagnosis is based on evaluation of history and clinical features, conventional radiology, and synovial fluid examination. Non-polarized light microscopy should be used initially to screen for CPPD crystals based upon their characteristic morphology, and compensated polarized light microscopy, showing the crystals to be weakly positive birefringent, is recommended for definitive identification, although this last pattern only occurs in about 20% of samples. The main goals of CPPD therapy are control of the acute or chronic inflammatory reaction and prevention of further episodes.

  5. Clinical radiodiagnosis of collagen diseases. Klinicheskaya rentgenodiagnostika kollagenozov

    Energy Technology Data Exchange (ETDEWEB)

    Spasskaya, P A; Bartusevichene, A S

    1988-01-01

    General information about collagen diseases, short history of their theory development are presented; classification is discussed. Pathomorphology of connective tissue and vessels in these diseases is described. Clinicoroentgenologic diagnosis of internal organ and locomotor system injuries in systemic lupus erythemotosus, in sclerodermia systematica, in dermatomyositis in combination with morphological and clinicolabaratory data is analysed in detail. 166 refs.; 85 figs.

  6. A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

    International Nuclear Information System (INIS)

    Severi, Gianluca; FitzGerald, Liesel M; Muller, David C; Pedersen, John; Longano, Anthony; Southey, Melissa C; Hopper, John L; English, Dallas R; Giles, Graham G; Mills, John

    2014-01-01

    Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” (N = 83), were matched to “referents” (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

  7. Tissue engineering and regenerative medicine in applied research: a year in review of 2014.

    Science.gov (United States)

    Lin, Xunxun; Huang, Jia; Shi, Yuan; Liu, Wei

    2015-04-01

    Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in applied researches of TERM area, including stem cell-mediated tissue regeneration, material science, and TERM clinical trial. These achievements demonstrated the great potential of clinical regenerative therapy of tissue/organ disease or defect through stem cells and tissue engineering approaches.

  8. Stem cell technology using bioceramics: hard tissue regeneration towards clinical application

    Directory of Open Access Journals (Sweden)

    Hiroe Ohnishi, Yasuaki Oda and Hajime Ohgushi

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs are adult stem cells which show differentiation capabilities toward various cell lineages. We have already used MSCs for treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose, culture expanded MSCs were combined with various ceramics and then implanted. Because of rejection response to allogeneic MSC implantation, we have utilized patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs, although the MSCs also exist in adipose tissue. When comparing osteogenic differentiation of these MSCs, bone marrow MSCs show more extensive bone forming capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone tissue regeneration. However, the MSCs show limited proliferation and differentiation capabilities that hindered clinical applications in some cases. Recent advances reveal that transduction of plural transcription factors into human adult cells results in generation of new type of stem cells called induced pluripotent stem cells (iPS cells. A drawback of the iPS cells for clinical applications is tumor formation after their in vivo implantation; therefore it is difficult to use iPS cells for the treatment. To circumvent the problem, we transduced a single factor of either SOX2 or NANOG into the MSCs and found high proliferation as well as osteogenic differentiation capabilities of the MSCs. The stem cells could be combined with bioceramics for clinical applications. Here, we summarize our recent technologies using adult stem cells in viewpoints of bone tissue regeneration.

  9. Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and persistence.

    Science.gov (United States)

    Deleage, Claire; Turkbey, Baris; Estes, Jacob D

    2016-08-01

    CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these cells residing within lymphoid tissue compartments throughout the body. Predictably, HIV-1 infection, replication, localization, reservoir establishment and persistence, as well as associated host immune and inflammatory responses and disease pathology principally take place within the tissues of the immune system. By virture of the fact that the virus-host struggle is played out within lymphoid and additional tissues compartments in HIV-1 infected individuals it is critical to understand HIV-1 infection and disease within these relevant tissue sites; however, there are obvious limitations to studying these dynamic processes in humans. Nonhuman primate (NHP) research has provided a vital bridge between basic and preclinical research and clinical studies, with experimental SIV infection of NHP models offering unique opportunities to understand key processes of HIV-1 infection and disease that are either not practically feasible or ethical in HIV-1 infected humans. In this review we will discuss current approaches to studying the tissue based immunopathogenesis of AIDS virus infection in NHPs, including both analyses of tissues obtained at biopsy or necropsy and complementary non-invasive imaging approaches that may have practical utility in monitoring HIV-1 disease in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Neuro degenerative diseases: clinical concerns

    International Nuclear Information System (INIS)

    Ibanez, V.

    2005-01-01

    Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [ 18 F]-deoxyglucose and [ 18 F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [ 18 F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [ 18 F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

  11. Water hardness and cardiovascular disease. Elements in water and human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Sharrett, A R

    1977-05-01

    The hypothesis that the hardness of drinking water has a causal role in the development of cardiovascular disease will be strengthened if it can be demonstrated that elements in drinking water find their way into human tissues in significant amounts. For biologically important metals, the evidence is reviewed for a relationship of tissue levels to levels in drinking water. Hard water can contribute significantly to daily magnesium intake. Residents of hard-water areas may have raised levels of magnesium in coronary arteries, bone, and myocardial tissue. Lead levels in bone and in blood have been shown to be elevated in individuals living in homes with lead plumbing and soft water. Cadmium intake from water is probably small compared to that from other sources, and there is no convincing evidence of alteration in human tissue levels via drinking water cadmium. Human zinc and copper tissue levels are of interest but have not been adequately studied in relation to drinking water levels.

  12. Chest Abnormalities in Juvenile-Onset Mixed Connective Tissue Disease: Assessment with High-Resolution Computed Tomography and Pulmonary Function Tests

    International Nuclear Information System (INIS)

    Aaloekken, T.M.; Mynarek, G.; Kolbenstvedt, A.; Lilleby, V.; Foerre, Oe.; Soeyseth, V.; Pripp, A.H.; Johansen, B.

    2009-01-01

    Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration

  13. Relationship with BSE (Mad Cow Disease)

    Science.gov (United States)

    ... Disease (CWD) Prion Diseases Relationship with BSE (Mad Cow Disease) Evidence Recommend on Facebook Tweet Share Compartir ... macaque monkeys inoculated with brain tissue obtained from cattle with BSE had clinical and neuropathological features strikingly ...

  14. Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

    Directory of Open Access Journals (Sweden)

    Ashkan Maccabi

    Full Text Available Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E, long term shear modulus (η, and time constant (τ in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

  15. Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

    Science.gov (United States)

    Maccabi, Ashkan; Shin, Andrew; Namiri, Nikan K; Bajwa, Neha; St John, Maie; Taylor, Zachary D; Grundfest, Warren; Saddik, George N

    2018-01-01

    Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

  16. Clinical evaluation of Synthetic Aperture Sequential Beamforming and Tissue Harmonic Imaging

    DEFF Research Database (Denmark)

    Brandt, Andreas Hjelm; Hemmsen, Martin Christian; Hansen, Peter Møller

    2014-01-01

    This study determines if the data reduction achieved by the combination Synthetic Aperture Sequential Beamforming (SASB) and Tissue Harmonic Imaging (THI) affects image quality. SASB-THI was evaluated against the combination of Dynamic Received Focusing and Tissue Harmonic Imaging (DRF-THI). A BK...... equally good image quality although a data reduction of 64 times is achieved with SASB-THI.......This study determines if the data reduction achieved by the combination Synthetic Aperture Sequential Beamforming (SASB) and Tissue Harmonic Imaging (THI) affects image quality. SASB-THI was evaluated against the combination of Dynamic Received Focusing and Tissue Harmonic Imaging (DRF-THI). A BK...... liver pathology were scanned to set a clinical condition, where ultrasonography is often performed. A total of 114 sequences were recorded and evaluated by five radiologists. The evaluators were blinded to the imaging technique, and each sequence was shown twice with different left-right positioning...

  17. Innate lymphoid cells in tissue homeostasis and diseases.

    Science.gov (United States)

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  18. Molecular and Genetic Basis of Hereditary Connective-Tissue Diseases Accompanied by Frequent Fractures

    Directory of Open Access Journals (Sweden)

    G. T. Yakhyaeva

    2016-01-01

    Full Text Available Frequent bone fractures in infancy require the elimination of a large number (> 100 of genetic disorders. The modern diagnostic method of hereditary diseases characterized by debilitating course is a new generation sequencing. The article presents the results of molecular-genetic study conducted in 18 patients with clinical symptoms of connective tissue disorders. 10 (56% patients had mutations in the genes encoding type I collagen chains, leading to the development of osteogenesis imperfecta, 5 (28% — mutations in IV and V type collagen genes that are responsible for the development of Ehlers-Danlos syndrome. 3 (17% patients had mutations in the gene encoding fibrillin-1 protein, deficiency of which is manifested by Marfan syndrome. However, the correlation between patient's phenotype and discovered mutations in the investigated gene is established not in all cases.

  19. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  20. Skin cancer risk in autoimmune connective tissue diseases.

    Science.gov (United States)

    Kostaki, D; Antonini, A; Peris, K; Fargnoli, M C

    2014-10-01

    Cutaneous malignancies have been significantly associated with autoimmune connective tissue diseases (ACTDs). This review focuses on the current state of knowledge on skin cancer risk in the most prevalent ACTDs in dermatology including lupus erythematosus, scleroderma, dermatomyositis and Sjögren syndrome. Potential pathogenetic mechanisms for the association between ACTDs and malignancy involve disease-related impairment of immune system, sustained cutaneous inflammation, drug-associated immune suppression and increased susceptibility to acquired viral infections. An additional causal role might be played by environmental factors such as UV exposure and smoking. The occurrence of skin cancer can have a profound impact on the already compromised quality of life of ACTD patients. Therefore, effective screening and monitoring strategies are essential for ACTD patients as early detection and prompt therapeutic intervention can reduce morbidity and mortality in these patients.

  1. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

    Directory of Open Access Journals (Sweden)

    Federica Novelli

    Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

  2. Clinical outcome of Crohn's disease according to the Vienna classification: disease location is a useful predictor of disease course

    NARCIS (Netherlands)

    Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

    2006-01-01

    OBJECTIVES: Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

  3. Clinical outcome of Crohn's disease according to the Vienna classification : disease location is a useful predictor of disease course

    NARCIS (Netherlands)

    Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

    Objectives Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

  4. Influence of Abutment Design on Clinical Status of Peri-Implant Tissues

    OpenAIRE

    Taiyeb-Ali, T. B.; Toh, C. G.; Siar, C. H.; Seiz, D.; Ong, S. T.

    2017-01-01

    Objective: To compare the clinical soft tissue responses around implant tooth-supported 3-unit bridges using tapered abutments with those using butt-joint abutments. Methods: In a split-mouth design study, 8 mm Ankylos (Dentsply Friadent, Germany) implants were placed in the second mandibular molar region of 8 adult Macaca fascicularis monkeys about I month after extraction of all mandibular molars. After 3 months of submerged healing, 3-unit metal bridges were constructed. Clinical data was ...

  5. Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

    International Nuclear Information System (INIS)

    Storch, A.

    2002-01-01

    Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

  6. Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

    Directory of Open Access Journals (Sweden)

    Sarah L. Tao

    2010-03-01

    Full Text Available One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

  7. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rajesh Joshi

    2015-01-01

    Full Text Available Objective: To determine the prevalence of celiac disease (CD in children with type 1 diabetes mellitus (TIDM in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them.

  8. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

  9. Select tissue mineralconcentrations and chronic wasting disease status in mule deer from north-central Colorado

    OpenAIRE

    Wolfe, Lisa L.; Conner, Mary M.; Bedwell, Cathy L.; Lukacs, Paul M.; Miller, Michael W.

    2010-01-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (≥2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populati...

  10. Pre-clinical MR elastography: Principles, techniques, and applications

    Science.gov (United States)

    Bayly, P. V.; Garbow, J. R.

    2018-06-01

    Magnetic resonance elastography (MRE) is a method for measuring the mechanical properties of soft tissue in vivo, non-invasively, by imaging propagating shear waves in the tissue. The speed and attenuation of waves depends on the elastic and dissipative properties of the underlying material. Tissue mechanical properties are essential for biomechanical models and simulations, and may serve as markers of disease, injury, development, or recovery. MRE is already established as a clinical technique for detecting and characterizing liver disease. The potential of MRE for diagnosing or characterizing disease in other organs, including brain, breast, and heart is an active research area. Studies involving MRE in the pre-clinical setting, in phantoms and artificial biomaterials, in the mouse, and in other mammals, are critical to the development of MRE as a robust, reliable, and useful modality.

  11. Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases

    International Nuclear Information System (INIS)

    Asaka, M.; Nagase, K.; Miyazaki, T.; Alpert, E.

    1983-01-01

    A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases

  12. Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease

    Directory of Open Access Journals (Sweden)

    Ju Huang

    2017-06-01

    Full Text Available Fabry disease is a rare lysosomal storage disorder (LSD. We designed multiple recombinant lentivirus vectors (LVs and tested their ability to engineer expression of human α-galactosidase A (α-gal A in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease.

  13. Trichinella infection and clinical disease

    DEFF Research Database (Denmark)

    Clausen, M R; Meyer, C N; Krantz, T

    1996-01-01

    Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of Trichinella species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning....... Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection....... The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed....

  14. Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010.

    Science.gov (United States)

    Elfving, P; Marjoniemi, O; Niinisalo, H; Kononoff, A; Arstila, L; Savolainen, E; Rutanen, J; Kaipiainen-Seppänen, O

    2016-07-01

    Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4-7.0), idiopathic inflammatory myopathies 1.9 (0.5-5.0), systemic sclerosis 4.4 (2.0-8.3), mixed connective tissue disease 1.0 (0.1-3.5), Sjögren's syndrome 10.7 (6.7-16.1) and undifferentiated connective tissue disease 13.6 (9.0-19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3-4.3), central nervous system vasculitis 0.5 (0-2.7) and Henoch-Schönlein purpura 1.5 (0.3-4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2-14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.

  15. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

  16. Clinical drug development using dynamic biomarkers to enable personalized health care in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Bihlet, Asger R; Karsdal, Morten A; Bay-Jensen, Anne-Christine

    2015-01-01

    Despite massive investments in development of novel treatments for heterogeneous diseases such as Chronic Obstructive Pulmonary Disease (COPD), the resources spent have only benefitted a fraction of the population treated. Personalized Health Care to guide selection of a suitable patient population...... at higher risk of progression. We review the role of extra-cellular matrix proteins found to be upregulated in COPD. Novel biomarkers of connective tissue remodeling which may provide added value for a personalized approach by detecting subgroups of patients with active disease suitable for pharmacological...... already in the clinical development of new compounds could offer a solution. In this review, we discuss past successes and failures in drug development and biomarker research in COPD. We describe research in COPD phenotypes, and the required characteristics of a suitable biomarker for identifying patients...

  17. Audit of Diabetic Soft Tissue Infection and Foot Disease in Accra ...

    African Journals Online (AJOL)

    BACKGROUND: Soft tissue infection and foot disease are well known complications among diabetes mellitus patients. With an increasing prevalence of diabetes mellitus in Africa, management of these complications is expected to become a major problem. OBJECTIVE: To audit the surgical management of diabetic

  18. Clinical Onset of Celiac Disease after an Episode of Campylobacter jejuni Enteritis

    Directory of Open Access Journals (Sweden)

    EF Verdu

    2007-01-01

    Full Text Available The present report describes a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies, serological markers for celiac disease (CD were evaluated. A positive tissue transglutaminase immunoglobulin A antibody test and repeat endoscopy with duodenal biopsy showing a Marsh IIIa lesion confirmed the diagnosis of CD. Infectious gastroenteritis is a well-established risk factor for the development of IBS, and there is recent evidence that it could play a role in the initiation and exacerbation of inflammatory bowel disease. The present case suggests that the clinical expression of CD can be unmasked by an acute gastrointestinal infection and supports the hypothesis that environmental factors other than gliadin may play a role in the clinical onset of CD in a genetically susceptible host. The increasing availability of serological testing and upper endoscopy has led to increasingly frequent diagnoses of CD and recognition that it may mimic IBS. The present case findings suggest that CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis.

  19. Celiac disease

    Directory of Open Access Journals (Sweden)

    Holtmeier Wolfgang

    2006-03-01

    Full Text Available Abstract Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen; often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years.

  20. Liver involvement in Gaucher disease - Review and clinical approach.

    Science.gov (United States)

    Adar, Tomer; Ilan, Yaron; Elstein, Deborah; Zimran, Ari

    2018-02-01

    Gaucher disease (GD), one of the most prevalent lysosomal storage diseases, is associated with glucocerebroside accumulation in cells of the monocyte-macrophage system in various organs, including the liver. Evaluating and managing liver disease in patients with Gaucher disease may be challenging. While hepatic involvement is common in Gaucher disease, its severity, and clinical significance span a wide spectrum, ranging from sub-clinical involvement to liver cirrhosis with its associated complications including portal hypertension. Apart from liver involvement in Gaucher disease, patients with may also suffer from other comorbidities involving the liver. That Gaucher disease itself can mimic hepatic lesions, affect laboratory tests used to characterize liver disease, and may be associated with non-cirrhotic portal hypertension, complicates the diagnostic approach even more. Better understanding of liver involvement in Gaucher disease can spare patients unnecessary invasive testing, and assist physicians in decision making when evaluating patients with Gaucher disease suspected for significant liver disease. This review describes the various clinical manifestations, laboratory and imaging abnormalities that may be encountered when following patients with Gaucher disease for liver involvement. The mechanism for liver disease are discussed, as well as the possible hepato-protective effect of glucocerebroside, and the a diagnostic and treatment approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Results of clinical approbation of new local treatment method in the complex therapy of inflammatory parodontium diseases

    Directory of Open Access Journals (Sweden)

    Yu. G. Romanova

    2017-08-01

    Full Text Available Treatment and prevention of inflammatory diseases of parodontium are one of the most difficult problems in stomatology today. Purpose of research: estimation of clinical efficiency of local combined application of developed agent apigel for oral cavity care and low-frequency electromagnetic field magnetotherapy at treatment of inflammatory diseases of parodontium. Materials and methods: 46 patients with chronic generalized catarrhal gingivitis and chronic generalized periodontitis of 1st degree were included into the study. Patients were divided into 2 groups depending on treatment management: basic (n = 23 and control (n = 23. Conventional treatment with the local use of the dental gel with camomile was used in the control group. Patients of the basic group were treated with local combined application of apigel and magnetotherapy. Efficiency was estimated with clinical, laboratory, microbiological and functional (ultrasonic Doppler examination methods of examination. Results: The application of the apigel and pulsating electromagnetic field in the complex medical treatment of patients with chronic generalized periodontitis (GhGP caused positive changes in clinical symptom and condition of parodontal tissues, that was accompanied by decline of hygienic and parodontal indexes. As compared with patients who had traditional anti-inflammatory therapy, patients who were treated with local application of apigel and magnetoterapy had decline of edema incidence. It was revealed that decrease of the pain correlated with improvement of hygienic condition of oral cavity and promoted prevention of bacterial contamination of damaged mucous membranes. Estimation of microvasculatory blood stream with the method of ultrasonic doppler flowmetry revealed more rapid normalization of volume and linear high systole, speed of blood stream in the parodontal tissues in case of use of new complex local method. Conclusions: Effect of the developed local agent in patients

  2. Periodontal disease in pregnant patients with rheumatic valvular disease: clinical and microbiological study.

    Science.gov (United States)

    Avila, Walkiria Samuel; Timerman, Lilia; Romito, Giuseppe Alexandre; Marcelino, Sílvia Linard; Neves, Itamara Lúcia Itagiba; Zugaib, Marcelo; Grinberg, Max

    2011-04-01

    The periodontal disease during pregnancy of women with rheumatic valve disease imply infective endocarditis risks and higher rate of preterm birth and low birth weight. To study the periodontal disease rate of women with rheumatic valve disease during pregnancy. We studied 140 pregnant women who included 70 patients with rheumatic valve disease and 70 healthy women. The periodontal examination included: 1) periodontal clinical exam regard the follow variables: a) probing depth; b) gingival margin; c) clinical attachment level; d) bleeding on probing; e) plaque index and f) gingival index; and 2) microbiological test was performed in samples serum and gingival crevicular fluid and considered positive controls to Porphyromonas gingivalis, Tannerella forsithia e Aggregobacter actinomycetemcomitans. Age and parity were similar between groups; as single or combined the mitral valve disease was prevalent among the rheumatic valve lesion in 45 (32.1%) e 20 (28.5%) cases, respectively. Among the periodontal variables gingival margin (p=0.01) and plaque index (p=0.04) were different between groups. The periodontal disease was identified in 20 (14,3%) pregnant women, seven (10%) of them were patients with valve rheumatic disease and the remain 13 (18,6%) were healthy women, its percentual was not different between groups (p=0,147). Microbiological analyses of oral samples showed higher percentual of P. gingivalis in healthy pregnant women (p=0.004). The clinical and microbiological study during pregnancy showed comparable incidence of periodontal disease between women with rheumatic valve disease and healthy women.

  3. Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

    Science.gov (United States)

    Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

    2016-07-11

    Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

  4. Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases

    Directory of Open Access Journals (Sweden)

    Zhiwei Hu

    2018-01-01

    Full Text Available Accumulating evidence suggests that tissue factor (TF is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD, endometriosis and rheumatoid arthritis (RA. Macrophage is involved in the progression of a variety of human diseases, such as atherosclerosis and viral infections (human immunodeficiency virus, HIV and Ebola. It is well documented that TF is selectively expressed on angiogenic vascular endothelial cells (VECs in these pathological angiogenesis-dependent human diseases and on disease-associated macrophages. Under physiology condition, TF is not expressed by quiescent VECs and monocytes but is solely restricted on some cells (such as pericytes that are located outside of blood circulation and the inner layer of blood vessel walls. Here, we summarize TF expression on angiogenic VECs, macrophages and other diseased cell types in these human diseases. In cancer, for example, the cancer cells also overexpress TF in solid cancers and leukemia. Moreover, our group recently reported that TF is also expressed by cancer-initiating stem cells (CSCs and can serve as a novel oncotarget for eradication of CSCs without drug resistance. Furthermore, we review and discuss two generations of TF-targeting therapeutic antibody-like immunoconjugates (ICON and L-ICON1 and antibody-drug conjugates that are currently being tested in preclinical and clinical studies for the treatment of some of these human diseases. If efficacy and safety are proven in current and future clinical trials, TF-targeting immunoconjugates may provide novel therapeutic approaches with potential to broadly impact the treatment regimen of these significant angiogenesis-dependent, as well as macrophage-associated, human diseases.

  5. Challenges and opportunities for tissue-engineering polarized epithelium.

    Science.gov (United States)

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  6. Tissue Engineering: Current Strategies and Future Directions

    OpenAIRE

    Olson, Jennifer L.; Atala, Anthony; Yoo, James J.

    2011-01-01

    Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue eng...

  7. A Dual Flow Bioreactor for Cartilage Tissue Engineering

    NARCIS (Netherlands)

    Spitters, Tim

    2014-01-01

    Preventing the onset of a degenerative disease like osteoarthritis by restoring tissue function before cartilage degradation occurs will decrease health costs, reduce socio-economic burdens of patients and preserve quality of life. However, producing ex vivo cartilage implants of clinically relevant

  8. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

    2017-06-15

    Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24

  9. Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans

    Science.gov (United States)

    Arora, Pooja; Sindhu, Annu; Dilbaghi, Neeraj; Chaudhury, Ashok; Rajakumar, Govindasamy; Rahuman, Abdul Abdul

    2012-01-01

    Nanotechnology is a fast growing area of research that aims to create nanomaterials or nanostructures development in stem cell and tissue-based therapies. Concepts and discoveries from the fields of bio nano research provide exciting opportunities of using stem cells for regeneration of tissues and organs. The application of nanotechnology to stem-cell biology would be able to address the challenges of disease therapeutics. This review covers the potential of nanotechnology approaches towards regenerative medicine. Furthermore, it focuses on current aspects of stem- and tissue-cell engineering. The magnetic nanoparticles-based applications in stem-cell research open new frontiers in cell and tissue engineering. PMID:22260258

  10. Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

    International Nuclear Information System (INIS)

    Guit, G.L.; Shaw, P.C.; Ehrlich, J.; Kroon, H.M.; Oudkerk, M.

    1985-01-01

    A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient

  11. Clinical relevance of precore mutations of hepatitis B virus in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Chaloska-Ivanova Viktorija

    2014-07-01

    Full Text Available Introduction: Hepatitis B is one of the most frequent etiological factors for chronic liver diseases worldwide. Recent studies have suggested the important role of the genetic diversity of the virus on natural course of hepatitis B. Hepatitis B e-antigen negative type of chronic hepatitis is associated with mutations in the precore region and basic core promoter of hepatitis B viral genome. Aim of study was to identify precore mutations in viral genome of patients with chronic hepatitis B and to evaluate clinical patterns of liver disease related to this type of hepatitis B. Methods: Sixty seven patients with hepatitis B were included in the study. In order to evaluate the clinical patterns of chronic liver disease related to hepatitis B viral infection, biochemical and virological investigations were done, as well as a quantification of serum viral load. All patients underwent liver biopsy and semiquantification of necroinflammation and/or fibrosis according to Knodell scoring was done. In the group of e antigen-negative patients, molecular analysis was performed in order to identify presence of mutations in precore region of the virus. Results: Study group was divided in 25 HBeAg-positive and 42 HBeAg-negative subjects. Al anin-aminotransferase activity and level of viral load were higher in HBeAg-positive (p < 0.05, but average age and histology activity index were significantly higher in the HBeAg-negative patients (p < 0.01. Precore mutants were found in 38 of 42 patients with HBeAg-negative hepatitis (90%. Fibrosis was found in 30/38 cases with mutations. Discussion: Mutations in precore region of HBV in HBeAg-negative patients were more prevalent in older age and were associated with higher rate of fibrosis in liver tissue, meaning more advanced stage of the disease. This could be a consequence of longer duration of HBV infection or more severe clinical course of the disease. Conclusion: Our results suggest that precore mutations are

  12. A New Resource for STD Clinical Providers: The Sexually Transmitted Diseases Clinical Consultation Network.

    Science.gov (United States)

    Caragol, Laura A; Wendel, Karen A; Anderson, Teri S; Burnside, Helen C; Finkenbinder, Allison; Fitch, John D; Kelley, Destiny H; Stewart, Terry W; Thrun, Mark; Rietmeijer, Cornelis A

    2017-08-01

    An online consultation tool, the Sexually Transmitted Diseases Clinical Consultation Network is a new resource for sexually transmitted disease clinicians and clinic managers. An initial evaluation shows that most requests (29%) were from medical doctors, followed by nurse practitioners (22%). Syphilis queries comprised 39% of consults followed by gonorrhea (12%) and chlamydia (11%).

  13. IMPULSIVE-COMPULSIVE DISORDERS IN PARKINSON'S DISEASE. CLINICAL CASES

    OpenAIRE

    N. V. Fedorova; A. V. Nikitina

    2015-01-01

    Objective – a description of clinical cases of impulsive­compulsive disorders in Parkinson,s disease. The first clinical case. Patient N., 75 years old, suffering for 15 years from Parkinson,s disease, akinetic­rigid form of the disease, stage 4 by Hyun–Yar. Since 2009, he received levodopa/carbidopa 250/25 mg 5 times/day (daily dose of 1250 mg of levodopa); pramipexole 3.5 mg per day (daily dose 3.5 mg), amantadine sulfate 100 mg 5 times/day (daily dose 500 mg). While taking antiparkinsonian...

  14. Automating the expert consensus paradigm for robust lung tissue classification

    Science.gov (United States)

    Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

    2012-03-01

    Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

  15. Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs

    DEFF Research Database (Denmark)

    Pedde, R. Daniel; Mirani, Bahram; Navaei, Ali

    2017-01-01

    , outlines the use of common biomaterials and advanced hybrid scaffolds, and describes several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. Finally, the applications...... of these biofabrication strategies in neural, skin, connective, and muscle tissue engineering are explored.......The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing...

  16. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

    Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

  17. Mixed connective tissue disease associated with noted pulmonary CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Souji; Tsukada, Atsuko; Furuya, Tatsutaka

    1984-10-01

    CT was performed in a 56-year-old woman with mixed connective tissue disease (MCTD). Much more definitive pulmonary findings were obtained by CT than by the conventional chest x-ray examination and pulmonary function test. CT findings disclosed pulmonary lesions extremely similar to those in cases of progressive systemic sclerosis. Pulmonary CT was considered useful in examining pulmonary lesions for MCTD.

  18. Clinical EPR: Unique Opportunities and Some Challenges

    Science.gov (United States)

    Swartz, Harold M.; Williams, Benjamin B.; Zaki, Bassem I.; Hartford, Alan C.; Jarvis, Lesley A.; Chen, Eunice; Comi, Richard J.; Ernstoff, Marc S.; Hou, Huagang; Khan, Nadeem; Swarts, Steven G.; Flood, Ann B.; Kuppusamy, Periannan

    2014-01-01

    Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice. PMID:24439333

  19. Unexpected MRI findings in clinically suspected Legg-Calve-Perthes disease

    Energy Technology Data Exchange (ETDEWEB)

    Lobert, Philip F.; Dillman, Jonathan R.; Strouse, Peter J.; Hernandez, Ramiro J. [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, C.S. Mott Children' s Hospital/F3503, Ann Arbor, MI (United States)

    2011-03-15

    In the setting of clinically suspected Legg-Calve-Perthes (LCP) disease and negative/equivocal radiographs, contrast-enhanced MRI can be performed to confirm the diagnosis. To determine the frequency of unexpected causes of hip pain as identified by MRI in children with clinically suspected LCP disease and negative/equivocal radiographs. All pediatric contrast-enhanced MRI examinations of the pelvis and hips performed between January 2000 and February 2009 to evaluate for possible LCP disease in the setting of negative/equivocal radiographs were identified. MRI examinations performed to evaluate for secondary avascular necrosis were excluded. Imaging reports were retrospectively reviewed for unexpected clinically important causes of hip pain. Thirty-six pediatric patients underwent contrast-enhanced MRI examinations for clinically suspected LCP disease in the setting of negative/equivocal radiographs. Twenty-two (61%) imaging studies were normal, while four (11%) imaging studies demonstrated findings consistent with LCP disease. Ten (28%) imaging studies revealed unexpected clinically important causes of hip pain, including nonspecific unilateral joint effusion and synovitis (n = 7, juvenile chronic arthritis was eventually diagnosed in 3 patients), sacral fracture (n = 1), apophyseal injury (n = 1), and femoral head subluxation (n = 1). MRI frequently reveals unexpected clinically important causes of hip pain in children with suspected LCP disease and negative/equivocal radiographs. (orig.)

  20. Infectious Disease Clinical Research Program (IDCRP)

    Data.gov (United States)

    Federal Laboratory Consortium — Our mission is to conduct infectious disease clinical research of importance to the military through a unique, adaptive, and collaborative network, to inform health...

  1. Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

    Directory of Open Access Journals (Sweden)

    Ben-Zhou Feng

    2016-04-01

    Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

  2. Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal

    NARCIS (Netherlands)

    Schwendicke, F.; Frencken, J.E.; Bjorndal, L.; Maltz, M.; Manton, D.J.; Ricketts, D.; Van Landuyt, K.; Banerjee, A.; Campus, G.; Domejean, S.; Fontana, M.; Leal, S.; Lo, E.; Machiulskiene, V.; Schulte, A.; Splieth, C.; Zandona, A.F.; Innes, N.P.

    2016-01-01

    The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental

  3. Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease

    DEFF Research Database (Denmark)

    Hansen, Dorte; Brock-Jacobsen, Bendt; Lund, Elisabeth

    2006-01-01

    OBJECTIVE: This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease. RESEARCH DESIGN AND METHODS: In a region comprising 24......% of the Danish population, all patients diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac...... a lower SD score (SDS) for height (P diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children

  4. Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F.; Bradna, P.; Pospisil, M.; Kubicek, J.; Vizda, J.; Kafka, P.; Palicka, V.; Mazurova, Y.

    1987-02-01

    Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

  5. Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F; Bradna, P; Pospisil, M; Kubicek, J; Vizda, J; Kafka, P; Palicka, V; Mazurova, Y

    1987-02-01

    Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

  6. DNA-abzymes in autoimmune diseases in clinic and experiment

    Directory of Open Access Journals (Sweden)

    T E Naumova

    2003-01-01

    Full Text Available DNA-abzymes enzymes in autoimmune diseases in clinic and experiment T.E. Naumova, O.M. Durova, A.G. Gabibov, Z.S. Alekberova, S. V. Suchkov DNA-hydrolyzing autoantibodies (AAB or DNA-abzymes can be found in autoimmune diseases in clinic and experiment. Technology of serum express screening for presence of DNA abzymes is described. Comparative study of DNA-hydrolising activity in patients with different forms of systemic and organ-specific autoimmune diseases was performed. Blood of clinically healthy donors was usually free of IgG DNA-abzymes. DNA-abzymes were most often revealed in patients with systemic lupus erythematosus (SLE and rheumatoid arthritis (RA less often in patients with organ-specific forms of autoimmune disturbances. The results of the study confirm the hypothesis of autoimmune origin of IgG DNA abzymes and demonstrate the possibility to use them in clinical practice for monitoring to disease activity in SLE and RA.

  7. Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Menno Pruijm

    2013-01-01

    Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

  8. Phenotype and Clinical Course of Inflammatory Bowel Disease with Co-Existent Celiac Disease.

    Science.gov (United States)

    Tse, Chung Sang; Deepak, Parakkal; De La Fuente, Jaime; Bledsoe, Adam C; Larson, Joseph J; Murray, Joseph A; Papadakis, Konstantinos A

    2018-05-07

    Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, and celiac disease are among the most common immune-mediated gastrointestinal diseases. We aim to elucidate the clinical course and outcomes of patients with concomitant inflammatory bowel disease and celiac disease, a unique population that remains scarcely studied to date. A retrospective matched case-control study of adults with coexistent inflammatory bowel disease and celiac disease was performed at a tertiary referral institution in North America. Logistic regression and Kaplan-Meier curves compared disease characteristics and clinical outcomes of the two groups. A total of 342 inflammatory bowel disease patients were included in this study, of which 114 had coexistent celiac disease and 228 did not. Patients with coexistent inflammatory bowel disease and celiac disease had higher rates of primary sclerosing cholangitis (19.3% vs 5.7%; odds ratio, 4.4; 95% confidence interval, 2.1-9.4; pceliac disease (10.5% vs 3.5%; odds ratio 3.2; 95% confidence interval 1.3-8.2; p=0.01), compared to patients without concomitant celiac disease. Patients with inflammatory bowel disease with concomitant celiac disease have unique phenotypic features compared to non-celiac inflammatory bowel disease, with higher risks for colitis-related hospitalizations, extensive colitis, and primary sclerosing cholangitis. Increased recognition of coexistent IBD and celiac disease can prompt clinicians to investigate for concomitant disease sooner, particularly in patients with seemingly refractory disease.

  9. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    KAUST Repository

    Gao, Zhao-Ming

    2015-06-11

    Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study.

  10. Evaluation of magnetization transfer ratios for breast tissues and breast diseases

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Fumio; Murai, Hiroshi; Takeuchi, Thouru; Iwase, Takuji; Miura, Shigeto; Mastushima, Shigeru; Oosaki, Hikaru [Aichi Cancer Center, Nagoya (Japan). Hospital; Kinosada, Yasuomi

    1997-03-01

    To determine MTRs for normal structures and benign diseases in the breast two-dimensional magnetization transfer imaging was performed in 62 patients and in 3 young female volunteers. With regard to the MTRs of measurements in the normal breast tissues, fat tissues which is close to simple cysts in MTRs show little transfer of longitudinal magnetization. MTRs of the muscles was 15.15{+-}6.22%, which exceeded those of breast parenchyma. The breast parenchyma didn`t show the change of MTR value due to the difference of patient age and due to variable amount of fat and fibrous tissues. Breast parenchyma in the two young volunteers clearly showed biphasic change of MTR values in accordance with the menstrual cycle; little transfer value was due to hydration in the postovulatory period and high transfer value was due to dehydration in the preovulatory period. In the remaining one volunteer during lactation period, mammary parenchyma shows sever decrease in MTR, because mammary gland is loaded with massive fluid, showing a very high signal intensity on First IR and T2-weighted images. MTR values of benign breast diseases including mastopathy, fibroadenoma and phyllodes tumor had no significant difference from those of the breast parenchyma and muscle. Non-invasive ductal carcinoma was equivalent to breast parenchyma in MTR. (K.H.)

  11. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  12. Tissue bionics: examples in biomimetic tissue engineering

    International Nuclear Information System (INIS)

    Green, David W

    2008-01-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

  13. Aberrant Expression of miRNA and mRNAs in Lesioned Tissues of Graves' Disease

    Directory of Open Access Journals (Sweden)

    Qiu Qin

    2015-03-01

    Full Text Available Background and Aims: Abnormal microRNA (miRNA expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD. Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. Methods: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls were also collected for further validation by quantitative real-time PCR ( qRT-PCR . Results: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC≥1.3 or≤0.77 and pConclusion: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.

  14. Hematologic manifestations of Crohn's disease: two clinical cases

    Directory of Open Access Journals (Sweden)

    O. V. Taratina

    2017-01-01

    Full Text Available Inflammatory bowel diseases (IBD are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a  combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind

  15. Mixed connective tissue disease associated with noted pulmonary CT findings

    International Nuclear Information System (INIS)

    Yamazaki, Souji; Tsukada, Atsuko; Furuya, Tatsutaka

    1984-01-01

    CT was performed in a 56-year-old woman with mixed connective tissue disease (MCTD). Much more definitive pulmonary findings were obtained by CT than by the conventional chest x-ray examination and pulmonary function test. CT findings disclosed pulmonary lesions extremely similar to those in cases of progressive systemic sclerosis. Pulmonary CT was considered useful in examining pulmonary lesions for MCTD. (Namekawa, K.)

  16. Mid-term clinical results of tissue-engineered vascular autografts

    International Nuclear Information System (INIS)

    Matsumura, Goki; Shin'oka, Toshiharu; Hibino, Narutoshi; Saito, Satoshi; Sakamoto, Takahiko; Ichihara, Yuki; Hobo, Kyoko; Miyamoto, Shin'ka; Kurosawa, Hiromi

    2007-01-01

    Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source. Since September 2001, tissue-engineered grafts seeded with autologous bone marrow cells have been implanted in 44 patients. The patients or their parents were fully informed and had given consent to the procedure. A 3 to 10 ml/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. The polymer tube serving as a scaffold for the cells was composed of a copolymer of lactide and ε-caprolactone (50:50) which degrades by hydrolysis. Polyglycolic or poly-l-lactic acid woven fabric was used for reinforcement. Twenty-six tissue-engineered conduits and 19 tissue-engineered patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median 7.4 years). All patients underwent a catheterization study, CT scan, or both, for evaluation after the operation. There were 4 late deaths due to heart failure with or without multiple organ failure or brain bleeding in this series; these were unrelated to the tissue-engineered graft function. One patient required percutaneous balloon angioplasty for tubular graft-stenosis and 4 patients for the stenosis of the patch-shaped tissue engineered material. Two patients required re-do operation; one for recurrent pulmonary stenosis and another for a resulting R-L shunt after the lateral tunnel method. Kaplan-Meier analysis in

  17. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Directory of Open Access Journals (Sweden)

    Hayley C Whitaker

    2010-10-01

    Full Text Available Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  18. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Science.gov (United States)

    Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

    2010-10-13

    Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  19. Disease Development and Symptom Expression of Xanthomonas axonopodis pv. citri in Various Citrus Plant Tissues.

    Science.gov (United States)

    Vernière, C J; Gottwald, T R; Pruvost, O

    2003-07-01

    ABSTRACT Experimental inoculations of Xanthomonas axonopodis pv. citri in different tissues of Tahiti lime and Pineapple sweet orange were conducted monthly under natural conditions on Réunion Island. The interactions between a set of environmental and epidemic variables associated with disease expression and 184 different factor combinations were investigated to determine the parameters needed to explain Asiatic citrus canker (ACC) disease expression. Area under the disease progress curve (AUDPC), inoculation date (Id), fruit and leaf age ratings (FAR and LAR), and number of days during the first 2 weeks postinoculation for which the temperature was less than 14 degrees C (T(min)) or more than 28 degrees C (T(max)) were retained by principal component analysis and canonical correlation analysis as the most meaningful epidemic and environmental variables, respectively. AUDPC as the strongest dependent variable and combinations of the environmental variables as independent variables were used in multiple regression analyses. Tissue age rating at the time of infection was a good predictor for disease resulting from spray inoculation on fruits and leaves and also on fruits following a wound inoculation. Temperature, as expressed by T(min) or T(max), was also a significant factor in determining disease development described by AUDPC. Mature green stems were highly susceptible after wounding, similarly to leaves, but buds and leaf scars expressed the lowest susceptibility. These variations in disease expression according to the tissues will have different impacts on ACC epidemiology.

  20. Oxidative stress and antioxidant activity in orbital fibroadipose tissue in Graves' ophthalmopathy.

    Science.gov (United States)

    Hondur, Ahmet; Konuk, Onur; Dincel, Aylin Sepici; Bilgihan, Ayse; Unal, Mehmet; Hasanreisoglu, Berati

    2008-05-01

    To investigate the oxidative stress and antioxidant activity in the orbit in Graves' ophthalmopathy (GO). Orbital fibroadipose tissue samples were obtained from 13 cases during orbital fat decompression surgery. All cases demonstrated features of moderate or severe GO according to the European Group on Graves' Orbitopathy classification. The disease activity was evaluated with the Clinical Activity Score, and the clinical features of GO were evaluated with the Ophthalmopathy Index. Orbital fibroadipose tissue samples of 8 patients without any thyroid or autoimmune disease were studied as controls. In the tissue samples, lipid hydroperoxide level was examined to determine the level of oxidative stress; glutathione level to determine antioxidant level; superoxide dismutase, glutathione reductase, and glutathione peroxidase activities to determine antioxidant activity. Lipid hydroperoxide level and all three antioxidant enzyme activities were found to be significantly elevated, while glutathione level significantly diminished in tissue samples from GO cases compared to controls (p < 0.05). Glutathione levels in tissue samples of GO cases showed negative correlation with Ophthalmopathy Index (r = -0.59, p < 0.05). The antioxidant activity in the orbit is enhanced in GO. However, the oxidative stress appears to be severe enough to deplete the tissue antioxidants and leads to oxidative tissue damage. This study may support the possible value of antioxidant treatment in GO.

  1. Necrotising soft tissue infection following mastectomy

    Directory of Open Access Journals (Sweden)

    Jackson P

    2010-03-01

    Full Text Available Necrotising fasciitis is a rare but rapidly progressive soft tissue disease which can lead to extensive necrosis, systemic sepsis and death. Including this case, only 7 other cases have been reported in the world literature with only 2 others affecting the patient post mastectomy.This 59 year old Caucasian lady presented with severe soft tissue infection soon after mastectomy, which was successfully treated with a combination of debridement, triangulation, VAC© dressing and skin grafting.Necrotising soft tissue infections following mastectomy are rapidly progressive and potentially extremely serious. It is essential that a high index of clinical suspicion is maintained together with prompt aggressive treatment in a multidisciplinary environment to prevent worsening physical and psychological sequelae.

  2. Assessment of liver fibrosis stage influence on clinical course of periodontal diseases in patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    О. М. Slaba

    2017-08-01

    Full Text Available The aim. To assess the influence of liver fibrosis stage on the clinical course of periodontal diseases in patients with chronic hepatitis C. Material and Methods. 122 patients with chronic hepatitis C, treated at the 7th department ofLvivRegionalInfectiousDiseasesHospital during 2013 – 2015 were included into dental investigation. The periodontal disease was diagnosed in accordance with the classification of M. F. Danilevsky (1994. The clinical condition of periodontium was assessed by the papillary marginal alveolar index (PMA in the modification ofParma, by the periodontal index – PI (AL Russel, 1956, by the Muhlemann and Son index – the degree of bleeding in the region of the gingival papilla (PBI. The stage of liver fibrosis was determined according to the medical history. The significance of the difference between two or more relative indicators was calculated using the Fisher test with the Metropolis algorithm. The correlation dependence between the clinical condition of periodontal tissues and the stage of liver fibrosis in patients with viral hepatitis C was studied using the Spearman rank correlation coefficient. Results. The highest percentage of patients with stage of liver fibrosis F0 (70.00 ± 15.28 % was registered in patients with healthy periodont, the lowest - in patients with generalized periodontitis of the third stage (7.89 ± 4.37 %. The highest frequency of patients with the stage of liver fibrosis F3 (73.68 ± 7.14 % was also observed in persons suffering from generalized periodontitis stage III (73.68 ± 7.14 %. Conclusions. The distribution of periodontal lesion severity statistically significant (p < 0.001 depended on the stage of liver fibrosis in patients with chronic hepatitis C. Direct (R = 0.70; p < 0.001 strong correlation between the clinical state of periodontal tissues and the stage of liver fibrosis in patients with chronic hepatitis C (using the Spearman rank correlation coefficient has been determined

  3. Primary extrahepatic hydatid cyst of the soft tissue: a case report

    Directory of Open Access Journals (Sweden)

    Guraya Salman

    2012-11-01

    Full Text Available Abstract Introduction Hydatid disease of the soft tissue is an exceedingly uncommon site to be affected by the tapeworm Echinococcus. The presentation is often vague and misleading. The diagnostic armamentarium has to be supplemented by a meticulously taken history and clinical examination. Case presentation The present case report describes a 33-year-old Saudi male with a painless swelling in the right buttock which turned out to be a primary hydatid disease of the soft tissue. The lump was successfully excised surgically and the patient had an uneventful discharge. Conclusion Surgical excision of the extrahepatic hydatid disease remains the mainstay of treatment; although medical treatment is available for the recurrent and disseminated disease.

  4. Clinical evaluation of guidelines and two-test approach for lyme disease

    NARCIS (Netherlands)

    Blaauw, A. A.; van Loon, A. M.; Schellekens, J. F.; Bijlsma, J. W.

    1999-01-01

    The diagnosis of Lyme disease should be based on objective clinical signs and symptoms. In a clinical study, we have evaluated whether the recommended two-step approach for serodiagnosis of Lyme disease is useful in daily clinical practice and can influence clinical decision making. The signs and

  5. Clinical Application of 18F-FDG PET in Alzheimer's Disease

    International Nuclear Information System (INIS)

    Ryu, Young Hoon

    2008-01-01

    PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. 18 F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, 18 F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers 18 F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of 18 F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases

  6. Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

    Science.gov (United States)

    von Mehren, Margaret; Randall, R Lor; Benjamin, Robert S; Boles, Sarah; Bui, Marilyn M; Conrad, Ernest U; Ganjoo, Kristen N; George, Suzanne; Gonzalez, Ricardo J; Heslin, Martin J; Kane, John M; Koon, Henry; Mayerson, Joel; McCarter, Martin; McGarry, Sean V; Meyer, Christian; O'Donnell, Richard J; Pappo, Alberto S; Paz, I Benjamin; Petersen, Ivy A; Pfeifer, John D; Riedel, Richard F; Schuetze, Scott; Schupak, Karen D; Schwartz, Herbert S; Tap, William D; Wayne, Jeffrey D; Bergman, Mary Anne; Scavone, Jillian

    2016-06-01

    Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy. Copyright © 2016 by the National Comprehensive Cancer Network.

  7. Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF, on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2, in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

  8. Myonecrosis of Behcet's disease

    International Nuclear Information System (INIS)

    Stubbs, Alana Y.; Taljanovic, Mihra S.; Massey, Brandon Z.; Graham, Anna R.; Friend, Christopher J.; Walsh, Joshua A.

    2008-01-01

    Behcet's disease is an inflammatory disease of unknown cause characterized by intermittent episodes of acute inflammation manifested by oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. We report a rare case of myonecrosis associated with Behcet's disease. Myonecrosis of Behcet's disease can mimic soft tissue abscess and therefore awareness of this entity in the appropriate clinical setting is important for initiation of appropriate and timely treatment. (orig.)

  9. Hydrogel based cartilaginous tissue regeneration: recent insights and technologies.

    Science.gov (United States)

    Chuah, Yon Jin; Peck, Yvonne; Lau, Jia En Josias; Hee, Hwan Tak; Wang, Dong-An

    2017-03-28

    Hydrogels have been extensively employed as an attractive biomaterial to address numerous existing challenges in the fields of regenerative medicine and research because of their unique properties such as the capability to encapsulate cells, high water content, ease of modification, low toxicity, injectability, in situ spatial fit and biocompatibility. These inherent properties have created many opportunities for hydrogels as a scaffold or a cell/drug carrier in tissue regeneration, especially in the field of cartilaginous tissue such as articular cartilage and intervertebral discs. A concise overview of the anatomy/physiology of these cartilaginous tissues and their pathophysiology, epidemiology and existing clinical treatments will be briefly described. This review article will discuss the current state-of-the-art of various polymers and developing strategies that are explored in establishing different technologies for cartilaginous tissue regeneration. In particular, an innovative approach to generate scaffold-free cartilaginous tissue via a transient hydrogel scaffolding system for disease modeling to pre-clinical trials will be examined. Following that, the article reviews numerous hydrogel-based medical implants used in clinical treatment of osteoarthritis and degenerated discs. Last but not least, the challenges and future directions of hydrogel based medical implants in the regeneration of cartilaginous tissue are also discussed.

  10. Clinical outcome and prognostic factors of primary gastric mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 77 cases

    International Nuclear Information System (INIS)

    Wang Shulian; Song Yongwen; Jin Jing; Wang Weihu; Liu Yueping; Liu Xinfan; Yu Zihao; Li Yexiong; Xue Liyan; Lv Ning

    2009-01-01

    Objective: To analyze the clinical results and prognostic factors of patients with early-stage primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Seventy-seven patients with primary gastric MALT lymphoma treated from 1985 to 2006 were retrospectively analyzed. All patients were pathologically confirmed as MALT lymphoma in stage I, II and II E (by modified Blackedge staging system). Thirty-seven patients had stage I disease, 23 stage II and 17 stage II E . Sixty patients underwent surgical resection and 17 received non-surgical treatment. Survival rates were calculated by the Kaplan-Meier analysis with the Logrank test. Results: With a median follow up of 57 months for the surviving patients (ranging from 1 to 198 months for all patients), the 5-year overall survival rate, disease-free survival rate, loco-regional control rate and distant metastasis free survival rate were 74%, 70%, 76% and 87%, respectively. In univariate analysis, clinical stage was significantly associated with overall survival. Patients with stage I or II disease had a better overall survival than those with stage II E (P=0.01). Tumor size and surgical resection were significantly associated with disease-free survival. Patients with primary tumor 8 cm or less in diameter had better disease-free survival than those with primary tumor more than 8 cm in diameter (P =0.03). Patients who underwent complete resection had better disease-free survival than those who underwent incomplete resection or no surgery (P=0.02). Clinical stage, tumor size and surgical resection were significantly associated with loco-regional control. Patients with stage I or II disease had better loco-regional control than those with stage II E (P=0.03). Patients with primary tumor 8 cm or less in diameter had better loco-regional control than those with primary tumor more than 8 cm in diameter (P=0.01). Patients who underwent complete resection had better loco-regional control than those who underwent

  11. [Clinical effect modified Chevron osteotomy combined with lateral tissue loosening in treating mild-moderate hallux valgus through internal signal approach].

    Science.gov (United States)

    Chen, Xue-Qiang; Wu, Qun-Feng; Dong, Wei-Qin; Yu, Li-Xin; Li, Xiong-Feng

    2018-03-25

    To explore clinical effect of modified Chevron osteotomy combined with lateral tissue loosening for the treatment of mild-moderate hallux valgus through internal signal approach. From July 2015 to June 2016, 26 patients with mild-moderate hallux valgus treated with modified Chevron osteotomy combined with lateral tissue loosening through internal signal approach, including 2 males and 24 females aged from 45 to 65 years old with an average of(54.6±4.8) years old;the courses of diseases ranged from 1 to 5 months with an average of (7.5±3.3) months. Hallux valgus angle(HVA), inter metatarsal angle(IMA) were measured at 12 months after operation, and AOFAS score was applied to evaluate clinical effect before and after operation. All incisions were healed at stage I. No incision occurred infection, metatarsal necrosis and recurrence of hallux valgus deformity. Two patients occurred skin numbness caused by musculocutaneous nerve injury. Twenty-six patients were followed up from 6 to 12 months with an average of(9.12±2.06) months. HVA, IMA were(30.01±3.71)°, (14.00±1.50)° before operation and(9.41±4.16)°, (7.00±0.60)° after operation, which had significant difference. There was statistical significance in AOFAS score before operation 54.77±9.59 and after operation 92.73±5.47, and 19 cases obtained excellent results and 7 moderate. Modified Chevron osteotomy combined with full thread headless pressure screw fixation and lateral tissue loosening for the treatment of mild-moderate hallux valgus has advantages of excellent exposure, simple operation, stable fixation, rapid recovery. Akin osteotomy with internal capsulorrhaphy were used with lateral loosening and could recover soft tissue balance between lateral and internal, and could receive satisfied clinical effects. Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.

  12. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    International Nuclear Information System (INIS)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-01-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results

  13. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-04-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

  14. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  15. [Interrelationship between lower limb varicosity, the grade of connective tissue dysplasia and atrial fibrillation in patients with coronary artery disease].

    Science.gov (United States)

    Forster, O V; Tsarev, O A; Shvarts, Iu G

    2006-01-01

    To determine interrelationship between lower limb varicosity, the clinical grade of non-differentiated dysplasia of the connective tissue and atrial fibrillation in patients with coronary artery disease (CAD). Altogether 156 coronary patients were examined. Persistent atrial fibrillation was present in 58 and chronic in 38 patients. The reference group comprised 60 patients without evident rhythm disorders in persons suffering from CAD. Markers of connective tissue dysplasia () were revealed on the part of the skeleton, joints skin and visceral organs. Lower limb varicosity was recorded as well. The number of the stigmas in the study groups was different. So, in the patient group without rhythm disorders, the mean number of the stigmas was equal to 3, which is a variant of normal. In the groups with persistent and constant AF, this indicator was equal to 4.7 and 5.2 respectively (patrial fibrilation there is a direct close correlation between the signs of connective tissue dysplasia and lower limb varicosity. In patients with persistent AF lower limb varicosity occurs more frequently than in CAD patients with normal rhythm.

  16. BILIRUBIN CONCENTRATIONS IN CLINICALLY HEALTHY AND DISEASED CAPTIVE WATERBUCK (KOBUS ELLIPSIPRYMNUS) AT THE SAN DIEGO ZOO SAFARI PARK.

    Science.gov (United States)

    Sadler, Ryan A; Lamberski, Nadine; Christopher, Mary M

    2016-06-01

    Captive waterbuck ( Kobus ellipsiprymnus ) that appear clinically healthy have been noted to have high serum bilirubin concentrations compared with other ruminants; however, questions remain about the physiologic factors affecting bilirubin concentration and its potential association with underlying disease and icteric serum or mucous membranes. Serum bilirubin concentrations of healthy and diseased waterbuck housed at the San Diego Zoo Safari Park from 1989 to 2012 were retrospectively analyzed to determine any link between icteric serum, total bilirubin concentration (tBili), and disease entities in this species. Total bilirubin and direct (dBili) bilirubin concentrations and the prevalence of icteric serum were compared by subspecies, age group, and health status; associations with complete blood count and biochemical results and clinical diagnosis were assessed. No significant differences were found in tBili or dBili between Ellipsen (n = 32) and Defassa (n = 29) subspecies or in juveniles (n = 22) versus adults (n = 39). Clinically healthy waterbuck (n = 40) had significantly higher tBili (mean ± 2SD, 7.9 ± 1.2 mg/dl; P bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues.

  17. Motor outcome measures in Huntington disease clinical trials.

    Science.gov (United States)

    Reilmann, Ralf; Schubert, Robin

    2017-01-01

    Deficits in motor function are a hallmark of Huntington disease (HD). The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) is a categoric clinical rating scale assessing multiple domains of motor disability in HD. The UHDRS-TMS or subsets of its items have served as primary or secondary endpoints in numerous clinical trials. In spite of a well-established video-based annual online certification system, intra- and interrater variability, subjective error, and rater-induced placebo effects remain a concern. In addition, the UHDRS-TMS was designed to primarily assess motor symptoms in manifest HD. Recently, advancement of technology resulted in the introduction of the objective Q-Motor (i.e., Quantitative-Motor) assessments in biomarker studies and clinical trials in HD. Q-Motor measures detected motor signs in blinded cross-sectional and longitudinal analyses of manifest, prodromal, and premanifest HD cohorts up to two decades before clinical diagnosis. In a multicenter clinical trial in HD, Q-Motor measures were more sensitive than the UHDRS-TMS and exhibited no placebo effects. Thus, Q-Motor measures are currently explored in several multicenter trials targeting both symptomatic and disease-modifying mechanisms. They may supplement the UHDRS-TMS, increase the sensitivity and reliability in proof-of-concept studies, and open the door for phenotype assessments in clinical trials in prodromal and premanifest HD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. IMPULSIVE-COMPULSIVE DISORDERS IN PARKINSON'S DISEASE. CLINICAL CASES

    Directory of Open Access Journals (Sweden)

    N. V. Fedorova

    2015-01-01

    Full Text Available Objective – a description of clinical cases of impulsive­compulsive disorders in Parkinson,s disease. The first clinical case. Patient N., 75 years old, suffering for 15 years from Parkinson,s disease, akinetic­rigid form of the disease, stage 4 by Hyun–Yar. Since 2009, he received levodopa/carbidopa 250/25 mg 5 times/day (daily dose of 1250 mg of levodopa; pramipexole 3.5 mg per day (daily dose 3.5 mg, amantadine sulfate 100 mg 5 times/day (daily dose 500 mg. While taking antiparkinsonian drugs the patient developed behavioral disorders such as dopamine disregulatory syndrome combined with punding, hypersexuality and compulsive shopping accompanied by visual hallucinations. The total equivalent dose of levodopa was 1600 mg per day. The second clinical case. Patient R., 52 years old, suffers from Parkinson,s disease about 5 years, a mixed form. She complained of slowness of movement, tremor in her left hand, sleep disturbances, poor mood. The clinic was appointed piribedil 50 mg 3 times per day. Despite the fact that the patient took only one of dopaminergic drugs in a therapeutic daily dose, she developed impulsive­compulsive disorder as hyper­ sexuality, compulsive shopping and binge eating. Results. In the first clinical case for correction of behavioral disorders in patients with Parkinson,s disease levodopa/carbidopa dose was reduced to 750 mg per day (3/4 Tab. 4 times a day; added to levodopa/benserazide dispersible 100 mg morning and levodopa/benserazide 100 mg before sleep (total dose of levodopa of 950 mg per day. Amantadine sulfate and pramipexole were canceled. It was added to the therapy of atypical neuroleptic clozapine dose 6,25 mg overnight. After 3 months marked improvement, regressed visual hallucina­ tions, improved family relationships, background mood became more stable. The patient continue to sing karaoke, but this hobby has be­ come less intrusive. In the second clinical event correction impulsive

  19. Alzheimer's disease: Cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies

    NARCIS (Netherlands)

    Marlatt, M.W.; Lucassen, P.J.; Perry, G.; Smith, M.A.; Zhu, X.

    2008-01-01

    Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and

  20. Tissue mortality by Caribbean ciliate infection and white band disease in three reef-building coral species

    Directory of Open Access Journals (Sweden)

    Alejandra Verde

    2016-07-01

    Full Text Available Caribbean ciliate infection (CCI and white band disease (WBD are diseases that affect a multitude of coral hosts and are associated with rapid rates of tissue losses, thus contributing to declining coral cover in Caribbean reefs. In this study we compared tissue mortality rates associated to CCI in three species of corals with different growth forms: Orbicella faveolata (massive-boulder, O. annularis (massive-columnar and Acropora cervicornis (branching. We also compared mortality rates in colonies of A. cervicornis bearing WBD and CCI. The study was conducted at two locations in Los Roques Archipelago National Park between April 2012 and March 2013. In A. cervicornis, the rate of tissue loss was similar between WBD (0.8 ± 1 mm/day, mean ± SD and CCI (0.7 ± 0.9 mm/day. However, mortality rate by CCI in A. cervicornis was faster than in the massive species O. faveolata (0.5 ± 0.6 mm/day and O. annularis (0.3 ± 0.3 mm/day. Tissue regeneration was at least fifteen times slower than the mortality rates for both diseases regardless of coral species. This is the first study providing coral tissue mortality and regeneration rates associated to CCI in colonies with massive morphologies, and it highlights the risks of further cover losses of the three most important reef-building species in the Caribbean.

  1. Clinical usefulness of facial soft tissues thickness measurement using 3D computed tomographic images

    International Nuclear Information System (INIS)

    Jeong, Ho Gul; Kim, Kee Deog; Hu, Kyung Seok; Lee, Jae Bum; Park, Hyok; Han, Seung Ho; Choi, Seong Ho; Kim, Chong Kwan; Park, Chang Seo

    2006-01-01

    To evaluate clinical usefulness of facial soft tissue thickness measurement using 3D computed tomographic images. One cadaver that had sound facial soft tissues was chosen for the study. The cadaver was scanned with a Helical CT under following scanning protocols about slice thickness and table speed: 3 mm and 3 mm/sec, 5 mm and 5 mm/sec, 7 mm and 7 mm/sec. The acquired data were reconstructed 1.5, 2.5, 3.5 mm reconstruction interval respectively and the images were transferred to a personal computer. Using a program developed to measure facial soft tissue thickness in 3D image, the facial soft tissue thickness was measured. After the ten-time repeation of the measurement for ten times, repeated measure analysis of variance (ANOVA) was adopted to compare and analyze the measurements using the three scanning protocols. Comparison according to the areas was analysed by Mann-Whitney test. There were no statistically significant intraobserver differences in the measurements of the facial soft tissue thickness using the three scanning protocols (p>0.05). There were no statistically significant differences between measurements in the 3 mm slice thickness and those in the 5 mm, 7 mm slice thickness (p>0.05). There were statistical differences in the 14 of the total 30 measured points in the 5 mm slice thickness and 22 in the 7 mm slice thickness. The facial soft tissue thickness measurement using 3D images of 7 mm slice thickness is acceptable clinically, but those of 5 mm slice thickness is recommended for the more accurate measurement

  2. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative

  3. Longitudinal analysis of quality of life in patients with undifferentiated connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Iudici M

    2017-02-01

    Full Text Available Michele Iudici, Rosaria Irace, Antonella Riccardi, Giovanna Cuomo, Serena Vettori, Gabriele Valentini Rheumatology Section, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Introduction/objectives: To prospectively assess the quality of life (QoL of patients affected by undifferentiated connective tissue diseases (UCTDs and to identify factors associated with changes over time.Patients and methods: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36 questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia.Results: At presentation, scores lower than the average of the general population were detected in 34 (74% and 41 (89% patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud’s phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p = 0.0009. No patient feature was found to be associated with the basal mental component summary score. During 24 months of follow-up, a significant improvement (ie, a change ≥5 from baseline in physical component summary and mental component summary scores was observed in 14 (33.3% and 20 (43.4% patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p < 0.001, while those who improved in the mental component more frequently had a history of either glucocorticoids (p = 0.043 or immunosuppressors (p = 0.037 intake during follow-up.Conclusion: UCTD patients perceive a worse QoL, regardless of Raynaud’s phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing

  4. Expressiveness and frequency differences of hip joint tissues pathomorphological changes in diseases complicated by femoroacetabular impingement syndrome

    Directory of Open Access Journals (Sweden)

    V. V. Grigorovsky

    2013-12-01

    Full Text Available Preface. Last years the increasing value in pathogenesis of hip joint osteoarthrosis (ОА both in adult patients and in children and teenagers is attached to articular surfaces congruence violation of the femoral head and acetabulum that is formed by articular cartilage and labrum, the last one by head movements in the maximum hip flexion and adduction enters in femoroacetabular impingement (FAI with edge of the head and allied site of the neck and is mechanically damaged. Purpose of the work. To establish hip joint tissues pathomorphological changes, to which FAI syndrome leads, and on the basis of graded expressiveness quantification of pathological changes to define differences of their occurrence frequency in groups of patients in some diseases with affected hip joint. Materials and research methods. 65 biopsies of hip joint tissues: proximal femoral epimetaphysis, acetabulum, acetabular lip and joint capsule –from patients with aseptic femoral head necrosis (АNFH and juvenile slipped femoral capital epiphysis (JSFCE. After study of qualitative features of hip joint tissues injury, some graded morphological indices characterizing conditions of affected joints, as occurrence frequencies of pathological changes of certain gradation, and also their comparison in groups of monitoring with calculation of their distinctions significance, were estimated. Results and their discussion. Clinical-pathomorphological research has revealed the various pathological changes shown by signs of discirculatory, chronic dystrophic-destructive and inflammatory processes in tissues of the femoral head, neck, acetabulum and joint capsule. FAI, causing secondary dystrophic-destructive changes in hip joint tissues, has different rates of development in various primary pathology: in JSCFE anatomic conditions of FAI develop faster, in АNFH – more slowly in the dynamics of secondary changes, the last ones do not differ statistically in various nosologies on rates

  5. Nailfold capillaroscopy in children and adolescents with rheumatic diseases.

    Science.gov (United States)

    Piotto, Daniela Gerent Petry; Len, Cláudio Arnaldo; Hilário, Maria Odete Esteves; Terreri, Maria Teresa Ramos Ascensão

    2012-10-01

    To assess nailfold capillaroscopy in children and adolescents with autoimmune rheumatic diseases (juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma and mixed connective tissue disease) and relate it to clinical and laboratory findings and disease activity. Cross-sectional study assessing 147 patients by use of nailfold capillaroscopy as follows: 60 with juvenile idiopathic arthritis; 30 with systemic lupus erythematosus; 30 with juvenile dermatomyositis; 20 with localized scleroderma; four with systemic sclerosis; and three with mixed connective tissue disease. Clinical and laboratory tests and nailfold capillaroscopy were performed in all patients. The nailfold capillaroscopy was performed with an optical microscope (at 10- and 16-time magnifications) by the same observer. Most patients (76.2%) had normal nailfold capillaroscopy. The major changes in nailfold capillaroscopy, characterizing the scleroderma pattern, were observed in patients with juvenile dermatomyositis, systemic scleroderma and mixed connective tissue disease. There was no association between nailfold capillaroscopy and disease activity in patients with juvenile idiopathic arthritis, systemic lupus erythematosus and localized scleroderma. Disease activity and capillaroscopy were associated in patients with juvenile dermatomyositis. Nailfold capillaroscopy is a useful method to diagnose autoimmune rheumatic diseases and monitor disease activity.

  6. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

  7. TOPICAL REVIEW: Stem cell technology using bioceramics: hard tissue regeneration towards clinical application

    Science.gov (United States)

    Ohnishi, Hiroe; Oda, Yasuaki; Ohgushi, Hajime

    2010-02-01

    Mesenchymal stem cells (MSCs) are adult stem cells which show differentiation capabilities toward various cell lineages. We have already used MSCs for treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose, culture expanded MSCs were combined with various ceramics and then implanted. Because of rejection response to allogeneic MSC implantation, we have utilized patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs, although the MSCs also exist in adipose tissue. When comparing osteogenic differentiation of these MSCs, bone marrow MSCs show more extensive bone forming capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone tissue regeneration. However, the MSCs show limited proliferation and differentiation capabilities that hindered clinical applications in some cases. Recent advances reveal that transduction of plural transcription factors into human adult cells results in generation of new type of stem cells called induced pluripotent stem cells (iPS cells). A drawback of the iPS cells for clinical applications is tumor formation after their in vivo implantation; therefore it is difficult to use iPS cells for the treatment. To circumvent the problem, we transduced a single factor of either SOX2 or NANOG into the MSCs and found high proliferation as well as osteogenic differentiation capabilities of the MSCs. The stem cells could be combined with bioceramics for clinical applications. Here, we summarize our recent technologies using adult stem cells in viewpoints of bone tissue regeneration.

  8. Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease

    Directory of Open Access Journals (Sweden)

    Moldovan Laura

    2010-10-01

    Full Text Available Abstract Background Computer-based teaching (CBT is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II. Aim To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. Implementation and Results The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca, was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. Conclusions The

  9. Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease.

    Science.gov (United States)

    Al-Jasmi, Fatma; Moldovan, Laura; Clarke, Joe T R

    2010-10-25

    Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II). To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. The Hunter disease eClinic employs a CBT model providing the trainee with realistic

  10. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

    Science.gov (United States)

    Ilus, T; Kaukinen, K; Virta, L J; Huhtala, H; Mäki, M; Kurppa, K; Heikkinen, M; Heikura, M; Hirsi, E; Jantunen, K; Moilanen, V; Nielsen, C; Puhto, M; Pölkki, H; Vihriälä, I; Collin, P

    2014-02-01

    Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully. © 2014 John Wiley & Sons Ltd.

  11. Imaging tissue hypoxia: clinical and pre-clinical experience with 123IAZA

    International Nuclear Information System (INIS)

    Wiebe, L.I.

    1997-01-01

    The molecular mechanisms that underline the selective binding of iodazomycin arabinoside, IAZA, and related nitromidazoles are reviewed as a basis for interpretation of preclinical and clinical data for hypoxic binding of radioiodinated IAZA. Clinical data are presented for 123 IAZA uptake in a number of pathologies including metastatic tumours, peripheral vascular disease in diabetes, muscle stress and rheumatoid arthritis. The results of studies to determine the influence of tumour type on uptake of 123 I-IAZA in patients with a variety of deep-seated solid tumours will be presented. Correlations of hypoxia-dependent binding with 99m Tc-HMPAO perfusion images will be reviewed and early correlations of uptake to treatment response in cancer will be presented. Unusual features of 123 I-IAZA biodistribution will also be discussed together with detailed pharmacokinetic and radiation dosimetry data for '2 123 I- IAZA in normal volunteers

  12. [The clinical and microbiological characteristics of oropharyngeal candidiasis in the HIV-infected patients at the late stages of the disease].

    Science.gov (United States)

    Charushin, A O; Elovikov, A M; Charushina, I P; Vorob'eva, N N; Katretskaya, G G

    Oropharyngeal candidiasis in 512 HIV-infected patients at the late stages of the disease was studied with special reference to the clinical and microbiological characteristics of this condition. The diagnosis was established based on the results of the clinical and microbiological examination of the patients including investigation of the tissue samples taken from the oral cavity and the throat with the use of the device specially developed for this purpose. It was shown that the disease existed in various clinical forms the most common of which were monocomponent pathology represented by pseudomembranous candidiasis in 37.5±2.14% of the patients, the two-component mixed form (pseudomembranous candidiasis with concomitant angular chelitis) diagnosed in 27.5±1.97% cases, and the ternary form (the combination of pseudomembranous candidiasis, acute atrophic process, and angular chelitis) documented in 11.9±1.43% patients. The main clinical features of the disease included the combination of its various forms, multiple localization of the pathological process, and its polymorphous manifestations. Changes in the clinical course of oropharyngeal candidiasis associated with the progression of HIV from the 4A to the 4B stage were detected for the first time. They were shown to be accompanied by variations in the species composition and concentration of fungal flora in the crypts of the palatine tonsils and its sensitivity to fluconazole therapy.

  13. HEREDITARY CONNECTIVE TISSUE DISORDERS: NOMENCLATURE AND DIAGNOSTIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    A. V. Klemenov

    2015-01-01

    Full Text Available Hereditary connective tissue disorders (HCTDs are a genetically and clinically diverse group of diseases, which encompasses common congenital disorders of fibrous connective tissue structures. Out of the whole variety of the clinical manifestations of NCTDs, only differentiated monogenic syndromes with the agreed guidelines for their diagnosis have been long the focus of the medical community’s attention. Many unclassified forms of the pathology (dysplasia phenotypes have been disregarded while assessing a person’s prognosis and defining treatment policy. With no clear definition of NCTDs or their approved diagnostic algorithm, it is difficult to study their real prevalence in the population, to compare literature data, and to constructively discuss various scientific and practical aspects of this disease. Efforts to systematize individual clinical types of NCTD and to formulate their diagnostic criteria are set forth in the All-Russian Research Society Expert Committee national guidelines approved in 2009 and revised in 2012. The paper gives current views on the nomenclature of NCTDs, considers diagnostic criteria for both classified monogenic syndromes (Marfan's syndrome, Ehlers–Danlos' syndrome, MASS phenotype, primary mitral valve prolapse, joint hypermobility syndrome and unclassified dysplasia phenotypes (MASS-like phenotype, marfanoid appearance, Ehlers–Danlos-like phenotype, benign joint hypermobility syndrome, unclassified phenotype. The above abnormalities are presented as a continuous list drawn up in the decreasing order of the degree of their clinical manifestations and prognostic value (the phenotypic continuum described by M.J. Glesby and R.E. Pyentz: from monogenic syndromes through dysplasia phenotypes to an unclassified phenotype. Emphasis is laid on the clinical NCTD identification difficulties associated with the lack of specificity of external and visceral markers of connective tissue asthenia and with the certain

  14. Nosocomial Legionnaires’ Disease: Clinical and Radiographic Patterns

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    Thomas J Marrie

    1992-01-01

    Full Text Available From 1981 to 1991, 55 patients (33 males, 22 females, mean age 58.6 years with nosocomial Legionnaires’ disease were studied. The mortality rate was 64%. One-half of the patients developed nosocomial Legionnaires’ disease within three weeks of admission. A surprising clinical feature was the low rate of findings of consolidation on physical examination, despite the fact that 52% of patients had this finding on chest radiograph. More than one-half of patients had pre-existing lung disease, rendering a radiographic diagnosis of pneumonia due to Legionella pneumophila impossible in 16% of cases despite microbiological confirmation. Nineteen per cent of patients who had blood cultures done had a pathogen other than L pneumophila isolated, suggesting dual infection in at least some of the patients. When the clinical and radiographic findings were combined it was noted that 40% of patients had one of three patterns suggestive of nosocomial Legionnaires’ disease: rapidly progressive pneumonia, lobar opacity and multiple peripheral opacities. However, in 60% of patients there were no distinctive features.

  15. Clinical significance of adrenal computed tomography in Addison's disease

    International Nuclear Information System (INIS)

    Sun, Zhong-Hua; Nomura, Kaoru; Toraya, Shohzoh; Ujihara, Makoto; Horiba, Nobuo; Suda, Toshihiro; Tsushima, Toshio; Demura, Hiroshi; Kono, Atsushi

    1992-01-01

    Adrenal computed tomographic (CT) scanning was conducted in twelve patients with Addison's disease during the clinical course. In tuberculous Addison's disease (n=8), three of four patients examined during the first two years after disease onset had bilaterally enlarged adrenals, while one of four had a unilaterally enlarged one. At least one adrenal gland was enlarged after onset in all six patients examined during the first four years. Thereafter, the adrenal glands was atrophied bilaterally, in contrast to adrenal glands in idiopathic Addison's disease which was atrophied bilaterally from disease onset (n=2). Adrenal calcification was a less sensitive clue in tracing pathogenesis, i.e., adrenal calcification was observed in five of eight patients with tuberculous Addison's disease, but not idiopathic patients. Thus, adrenal CT scanning could show the etiology of Addison's disease (infection or autoimmunity) and the phase of Addison's disease secondary to tuberculosis, which may be clinically important for initiating antituberculous treatment. (author)

  16. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  17. Hotspots in clinical management of severe liver diseases

    Directory of Open Access Journals (Sweden)

    LYU Jiayu

    2017-09-01

    Full Text Available Severe liver diseases such as liver failure and acute decompensated cirrhosis have critical conditions and high mortality rates, and the prognosis of such patients is closely associated with early warning, timely dynamic assessment, and comprehensive and effective therapy. The patients require a series of effective clinical management measures for elimination of causative factors, organ support, and prevention and treatment of complications. Medical treatment-artificial liver-liver transplantation is an important modality for severe liver diseases. Granulocyte colony-stimulating factor, stem cell therapy, and bioartificial liver have a promising future, while there are still controversies over non-selective β-blocker. This article reviews the hotspots in the clinical management of severe liver diseases.

  18. Cytokines and Liver Diseases

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    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  19. Clinical indicators to monitor patients with risk for ineffective cerebral tissue perfusion

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    Miriam de Abreu Almeida

    2015-04-01

    Full Text Available Objective. Select and validate the clinical indicators to monitor patients on risk for ineffective cerebral tissue perfusion, according to the Nursing Outcomes Classification (NOC. Methodology. Validation study carried out between November 2012 and August 2013, in a Brazilian hospital. Seventeen judges nurses evaluated the clinical indicators of Nursing Outcomes, according to NOC for patients on risk for ineffective cerebral tissue perfusion. In the first stage, were selected the nursing results for the assessment of the studied diagnosis and, in the second nurses assessment the importance of the indicators of the validated results in the previous step through a five points Likert scale (1 = not important to 5 = extremely important. Were used the content validity index (CVI that corresponds to the calculation of weighted averages of them marks awarded for each indicator, as it considered the following weights: 1=0.00, 2=0.25, 3=0.50; 4=0.75; 5=1.00. For categorization, the CVI considered as critical = ≥0.80; supplementary =≥0.50 to 0.79 and were disposed results <0.50. Results. Of the 9 nursing results, only the cerebral tissue perfusion obtained a 100% consensus. The CVI of the 18 indicators of this result showed that five were validated as critical (impaired neurological reflexes, systolic blood pressure, diastolic blood pressure, reduced level of consciousness and mean arterial pressure, 12 were validated as supplementary (Agitation, Impaired cognition, Intracranial pressure, Syncope, Vomiting, Findings of cerebral angiography, Headache, Restlessness, Fever, Unexplained anxiety, listlessness and Hiccughs and one was disposed (carotid bruit. Conclusions. The validation of information about the conditions of risk may allow early intervention to minimize the consequences of ineffective cerebral tissue perfusion.

  20. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qiongshi Lu

    2017-07-01

    Full Text Available Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD. Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  1. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Science.gov (United States)

    Lu, Qiongshi; Powles, Ryan L; Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

    2017-07-01

    Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  2. Mesenchymal Stem Cells in Tissue Repair

    Directory of Open Access Journals (Sweden)

    Amy M DiMarino

    2013-09-01

    Full Text Available The advent of mesenchymal stem cell (MSC based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC and quality assurance (QA are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

  3. [Connective tissue dysplasia in patients with celiac desease as a problem of violation of adaptation reserve islands of the body].

    Science.gov (United States)

    Tkachenko, E; Oreshko, L S; Soloveva, E A; Shabanova, A A; Zhuravleva, M S

    2015-01-01

    Clinically significant dysplasia of connective tissue in patients with celiac disease is often responsible for various visceral disorders. Different disturbances of motor and evacuation functions are often determined in this patients (gastroesophageal reflux, duodenogastral reflux, spastic and hyperkinetic dyskinesia). The clinical course of the celiac disease, associated with connective tissue dysplasia, is characterized by asthenovegetative syndrome, reduced tolerance to physical activity, general weakness, fatigue and emotional instability. These data should be considered in choosing a treatment.

  4. Clinical evaluation of oropharyngeal dysphagia in Machado-Joseph disease

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    Sabrina Mello Alves Corrêa

    2010-12-01

    Full Text Available CONTEXT: In Machado-Joseph disease, poor posture, dystonia and peripheral neuropathy are extremely predisposing to oropharyngeal dysphagia, which is more commonly associated with muscular dystrophy. OBJECTIVE: To evaluate the clinical characteristics of oropharyngeal dysphagia in Machado-Joseph disease patients. METHOD: Forty individuals participated in this study, including 20 with no clinical complaints and 20 dysphagic patients with Machado-Joseph disease of clinical type 1, who were all similar in terms of gender distribution, average age, and cognitive function. The medical history of each patient was reviewed and each subject underwent a clinical evaluation of deglutition. At the end, the profile of dysphagia in patients with Machado-Joseph disease was classified according to the Severity Scale of Dysphagia, as described by O'Neil and collaborators. RESULTS: Comparison between dysphagic patients and controls did not reveal many significant differences with respect to the clinical evaluation of the oral phase of deglutition, since afflicted patients only demonstrated deficits related to the protrusion, retraction and tonus of the tongue. However, several significant differences were observed with respect to the pharyngeal phase. Dysphagic patients presented pharyngeal stasis during deglutition of liquids and solids, accompanied by coughing and/or choking as well as penetration and/or aspiration; these signs were absent in the controls. CONCLUSIONS: Oropharyngeal dysphagia is part of the Machado-Joseph disease since the first neurological manifestations. There is greater involvement of the pharyngeal phase, in relation to oral phase of the deglutition. The dysphagia of these patients is classified between mild and moderate.

  5. Localization of microfibrillar-associated protein 4 (MFAP4 in human tissues: clinical evaluation of serum MFAP4 and its association with various cardiovascular conditions.

    Directory of Open Access Journals (Sweden)

    Helle Wulf-Johansson

    Full Text Available Microfibrillar-associated protein 4 (MFAP4 is located in the extracellular matrix (ECM. We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG, and osteopontin (OPN. Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI, 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease, 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive, and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative. Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05. Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05. In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244 and OPG (ρ = 0.62; p = 0.0014 were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions

  6. Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

    NARCIS (Netherlands)

    van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

    2010-01-01

    OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

  7. Meningococcal disease, a clinical and epidemiological review.

    Science.gov (United States)

    Batista, Rodrigo Siqueira; Gomes, Andréia Patrícia; Dutra Gazineo, Jorge Luiz; Balbino Miguel, Paulo Sérgio; Santana, Luiz Alberto; Oliveira, Lisa; Geller, Mauro

    2017-11-01

    Meningococcal disease is the acute infection caused by Neisseria meningitidis, which has humans as the only natural host. The disease is widespread around the globe and is known for its epidemical potential and high rates of lethality and morbidity. The highest number of cases of the disease is registered in the semi-arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional outbreaks, epidemics and sporadic cases occurring throughout the year, especially in the winter. The major epidemics of the disease occurred in Brazil in the 70's caused by serogroups A and C. Serogroups B, C and Y represent the majority of cases in Europe, the Americas and Australia. However, there has been a growing increase in serogroup W in some areas. The pathogen transmission happens for respiratory route (droplets) and clinically can lead to meningitis and sepsis (meningococcemia). The treatment is made with antimicrobial and supportive care. For successful prevention, we have some measures like vaccination, chemoprophylaxis and droplets' precautions. In this review, we have described and clarify clinical features of the disease caused by N. meningitidis regarding its relevance for healthcare professionals. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  8. Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models.

    Science.gov (United States)

    Finch, Paul W; Mark Cross, Lawrence J; McAuley, Daniel F; Farrell, Catherine L

    2013-09-01

    Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre-clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre-clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre-clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  9. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients

    Directory of Open Access Journals (Sweden)

    Hanae Takatsuki, PhD

    2016-10-01

    Full Text Available Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 106/g SD50 did not exist the infectivity.

  10. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  11. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    International Nuclear Information System (INIS)

    Gimpel, Charlotte; Pohl, Martin; Jung, Bernd A.; Jung, Sabine; Brado, Johannes; Odening, Katja E.; Schwendinger, Daniel; Burkhardt, Barbara; Geiger, Julia; Arnold, Raoul

    2017-01-01

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  12. The evaluation of clinical usefulness of transbrochoscopic lung biopsy in undefined interstitial lung diseases: a retrospective study.

    Science.gov (United States)

    Han, Qian; Luo, Qun; Chen, Xiaobo; Xie, Jiaxing; Wu, Lulu; Chen, Rongchang

    2017-03-01

    Previous studies mostly focused on the diagnostic accuracy of transbronchoscopic lung biopsy (TBLB) in the diagnosis of interstitial lung diseases (ILDs). We aimed to explore the clinical usefulness of TBLB results in the diagnostic procedure of undefined ILDs. The retrospective analysis included patients undergoing TBLB for the diagnosis of undefined ILDs from January 2007 to December 2010. The clinically useful TBLB was defined as that lead to a specific histopathological diagnosis or that was consistent with the working diagnosis based on existing clinical and radiological data. A total of 664 patients were included in the study. TBLB failed to obtain lung parenchyma in 155 cases (23.3%). TBLB was considered clinically helpful in 202 procedures (30.4%), including 114 cases that provided definitive histopathological diagnoses and 88 cases that were consistent with working diagnoses. Among 202 cases of clinically useful TBLBs, the majority were diagnosed as pulmonary alveolar proteinosis (PAP) (67 cases, 33.2%), connective tissue disease-related ILDs (CTD-ILDs) (65, 32.2%) and idiopathic pulmonary fibrosis (IPF) (33, 16.3%). Although TBLB could provide definitive histopathological diagnoses in all cases diagnosed as PAP, only few cases of IPF (7, 21.2% of IPF diagnoses) and CTD-ILDs (9, 13.8% of CTD-ILD diagnoses) could be identified by TBLBs. The clinical usefulness of TBLB, in conjunction with thorough clinical and radiological data, in the diagnosis of ILDs may be varied depending on different subtypes. The use of histopathological analysis and the type of biopsy employed should therefore be considered on a case-by-case basis. © 2015 John Wiley & Sons Ltd.

  13. Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

    Science.gov (United States)

    Cooper, Lilli; Seth, Rohit; Rhodes, Elizabeth; Alousi, Mohammed; Sivakumar, Bran

    2017-01-01

    Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Simplifying Skin Disease Diagnosis with Topical Nanotechnology.

    Science.gov (United States)

    Yeo, David C; Xu, Chenjie

    2018-05-01

    A new study published in the journal Nature Biomedical Engineering 1 documents a novel diagnostic technology that exploits topically applied nanotechnology to detect skin tissue biomarkers for diagnosis. This concept is demonstrated by noninvasively imaging connective tissue growth factor (CTGF) mRNA in abnormal scar cells, whole tissue, and animal models. In this commentary, we highlight the main findings and discuss their implications. Successful implementation in the clinic could give rise to self-applied, biopsy-free diagnostic technology and significantly reduce healthcare burden. Crucially, noninvasive visualization of disease biomarkers, mobile device signal acquisition, and Internet-enabled transmission could significantly transform the diagnosis of skin disease and other superficial tissues.

  15. Neutron activation analysis of the central nervous system tissues in neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, Masayuki; Ota, Kiichiro [Wakayama Medical Coll. (Japan); Sasajima, Kazuhisa

    1994-07-01

    As the diseases due to excessive metals in living bodies and the metals of their causes, Minamata disease due to Hg, itai-itai disease due to Cd, dialysis brain disease due to Al, hemochromatosis due to Fe, Wilson disease due to Cu and so on have been known. Also as the neural diseases, in which the possibility that metals take part in them is presumed, there are amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, Parkinsonism dementia and so on. In order to know the causes of the diseases due to excessive metals in living bodies and neurological diseases, the authors have measured Cu, Ca, Al, Mn, Zn and Fe in central nervous system tissues by activation analysis nondestructive method. The cases investigated were 4 cases of hepatocerebral diseases, 6 cases of ALS, 4 cases of Parkinson disease, 4 cases of Parkinsonism dementia, 4 cases of multiple sclerosis and 5 cases without CNS disease for the control. The method of measurement is described. The results for respective diseases are reported. Cu and Fe are in the relation of mirror images, and Cu formed Cu-superoxide dismutase (SOD) similarly to Zn and Mn as SOD carrier metals, and protects living bodies and CNS from oxidative stress. (K.I.).

  16. Huntington's disease: a clinical review

    Directory of Open Access Journals (Sweden)

    Roos Raymund AC

    2010-12-01

    Full Text Available Abstract Huntington disease (HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD. The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which

  17. Wear measurement of dental tissues and materials in clinical studies: A systematic review.

    Science.gov (United States)

    Wulfman, C; Koenig, V; Mainjot, A K

    2018-06-01

    This study aims to systematically review the different methods used for wear measurement of dental tissues and materials in clinical studies, their relevance and reliability in terms of accuracy and precision, and the performance of the different steps of the workflow taken independently. An exhaustive search of clinical studies related to wear of dental tissues and materials reporting a quantitative measurement method was conducted. MedLine, Embase, Scopus, Cochrane Library and Web of Science databases were used. Prospective studies, pilot studies and case series (>10 patients), as long as they contained a description of wear measurement methodology. Only studies published after 1995 were considered. After duplicates' removal, 495 studies were identified, and 41 remained for quantitative analysis. Thirty-four described wear-measurement protocols, using digital profilometry and superimposition, whereas 7 used alternative protocols. A specific form was designed to analyze the risk of bias. The methods were described in terms of material analyzed; study design; device used for surface acquisition; matching software details and settings; type of analysis (vertical height-loss measurement vs volume loss measurement); type of area investigated (entire occlusal area or selective areas); and results. There is a need of standardization of clinical wear measurement. Current methods exhibit accuracy, which is not sufficient to monitor wear of restorative materials and tooth tissues. Their performance could be improved, notably limiting the use of replicas, using standardized calibration procedures and positive controls, optimizing the settings of scanners and matching softwares, and taking into account unusable data. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

  18. TH-AB-209-12: Tissue Equivalent Phantom with Excised Human Tissue for Assessing Clinical Capabilities of Coherent Scatter Imaging Applications

    Energy Technology Data Exchange (ETDEWEB)

    Albanese, K; Morris, R; Spencer, J [Medical Physics Graduate Program, Duke University, Durham, NC (United States); Greenberg, J [Dept. of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Kapadia, A [Carl E Ravin Advanced Imaging Laboratories, Durham, NC (United States)

    2016-06-15

    Purpose: Previously we reported the development of anthropomorphic tissue-equivalent scatter phantoms of the human breast. Here we present the first results from the scatter imaging of the tissue equivalent breast phantoms for breast cancer diagnosis. Methods: A breast phantom was designed to assess the capability of coded aperture coherent x-ray scatter imaging to classify different types of breast tissue (adipose, fibroglandular, tumor). The phantom geometry was obtained from a prone breast geometry scanned on a dedicated breast CT system. The phantom was 3D printed using the segmented DICOM breast CT data. The 3D breast phantom was filled with lard (as a surrogate for adipose tissue) and scanned in different geometries alongside excised human breast tissues (obtained from lumpectomy and mastectomy procedures). The raw data were reconstructed using a model-based reconstruction algorithm and yielded the location and form factor (i.e., momentum transfer (q) spectrum) of the materials that were imaged. The measured material form factors were then compared to the ground truth measurements acquired by x-ray diffraction (XRD) imaging. Results: Our scatter imaging system was able to define the location and composition of the various materials and tissues within the phantom. Cancerous breast tissue was detected and classified through automated spectral matching and an 86% correlation threshold. The total scan time for the sample was approximately 10 minutes and approaches workflow times for clinical use in intra-operative or other diagnostic tasks. Conclusion: This work demonstrates the first results from an anthropomorphic tissue equivalent scatter phantom to characterize a coherent scatter imaging system. The functionality of the system shows promise in applications such as intra-operative margin detection or virtual biopsy in the diagnosis of breast cancer. Future work includes using additional patient-derived tissues (e.g., human fat), and modeling additional organs

  19. Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: observations from a proof-of-concept randomized clinical trial of cytokine blockade.

    LENUS (Irish Health Repository)

    Rooney, Terence

    2012-02-01

    The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-kappabeta ligand (RANKL) and osteoprotegerin (OPG) as biomarkers of disease activity, progressive joint damage, and therapeutic response, during cytokine blockade in rheumatoid arthritis (RA). Patients with active RA entered a randomized open-label 12-month study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 mug\\/kg twice weekly. Arthroscopic synovial tissue biopsies were obtained at baseline, at 4 weeks and at the final time point. Following immunohistochemical staining, RANKL and OPG expression was quantified using digital image analysis. Radiographic damage was evaluated using the van der Heijde modification of the Sharp scoring system. Twenty-two patients were randomized. Baseline expression of RANKL, but not OPG, correlated significantly with baseline CRP levels (r = 0.61, P < 0.01). While a significant reduction in OPG expression following treatment was observed in clinical responders at the final time point (P < 0.05 vs. baseline), RANKL levels did not change, and the RANKL:OPG ratio remained unaltered, even at the highest levels of clinical response. When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL expression is associated with progressive joint erosion, and may be independent of the clinical response to targeted therapy. The potential therapeutic importance of modulating RANKL in RA is highlighted, if radiographic arrest is to be achieved.

  20. About tendon tissue regeneration in experimental radiation disease

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D; Trichkova, P

    1976-01-01

    Under the conditions of experimental acute radiation disease the authors study the tendon tissue regeneration after suture of the lateral part of the gastrocnemius muscle tendon. Tendon auto and alloplasty were applied. In four postoperative periods the histological features are described in details as well as the characteristic phenomena observed during the regeneration influenced to a considerable degree by the irradiation. Round cell infiltration, large necrotic zones, erythrocyte infiltrations as well as predominance of non-specific tendon regeneration long after the surgery characterize the recovery period of the traumatically damaged tendon, nevertheless that at the end there is real tendon regeneration even though in a longer period in comparison with the controls (non-irradiated animals).

  1. Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review.

    Science.gov (United States)

    Nguyen, Patricia K; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C

    2016-11-01

    Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist. To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included. One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

  2. Pulsed-wave tissue Doppler and color tissue Doppler echocardiography: calibration with M-mode, agreement, and reproducibility in a clinical setting

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Jons, Christian; Fritz-Hansen, Thomas

    2009-01-01

    BACKGROUND: Myocardial velocities can be measured with both pulsed-wave tissue Doppler (PWTD) and color tissue Doppler (CTD) echocardiography. We aimed to (A) to explore which of the two methods better approximates true tissue motion and (B) to examine the agreement and the reproducibility...... of the two methods in a routine clinical setting. METHODS: For Study A, the displacements of 63 basal myocardial segments from 13 patients were examined with M-mode and compared with the velocity-time integral of PWTD and CTD velocities. For Study B, the basal lateral segments from 58 patients were examined...... with PWTD and CTD, and the peak myocardial velocities during systole (Sm), early diastole (Em), and late diastole (Am) were measured. RESULTS: Study A: CTD-based measurements of displacement were 12% lower than M-mode measurements (95% CI: -18%; -6%). PWTD velocity-time integrals measured at the outer edge...

  3. Ethical clinical translation of stem cell interventions for neurologic disease

    DEFF Research Database (Denmark)

    Cote, David J; Bredenoord, Annelien L; Smith, Timothy R

    2017-01-01

    The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested...... in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations...... are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell...

  4. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  5. Bridging the Gap between Research and Clinical Practice in Asymptomatic Alzheimer's Disease.

    Science.gov (United States)

    Downing, A M; Yaari, R; Ball, D E; Selzler, K J; Devous, M D

    2016-01-01

    Due to the growing global health impact of Alzheimer's disease (AD), there is a greater need for interventions that prevent or delay the onset of clinical symptoms of this debilitating disease. Clinical trials for disease-modifying compounds in AD have shifted towards earlier stages in the spectrum of illness, including the stage prior to cognitive symptoms. A population of specific interest for clinical research includes individuals with evidence of Alzheimer's disease pathology who are asymptomatic (ADPa). The challenges and barriers regarding medical treatment of ADPa must be identified and addressed prior to the completion of a positive clinical trial in order to accelerate the translation of research findings to clinical practice. This report applies an existing public health impact model from Spencer and colleagues (2013) to evaluate the readiness of the clinical practice environment to treat ADPa individuals if a disease-modifying agent achieves approval. We contrast the current clinical practice environment with a potential future state through investigating the effectiveness, reach, feasibility, sustainability, and transferability of the practice of treating ADPa individuals.

  6. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

    Science.gov (United States)

    Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

    2015-04-15

    The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifested. This literature search is performed because DiseaseConnect web server does not discriminate between pathologies emerging before, concomitantly or after infertility is manifested. Data show that different infertility etiologies not only share particular genes and/or molecular pathways with other pathologies but they have distinct clinical relationships with other diseases appearing after infertility is manifested. In particular, (1) testicular and high-grade prostate cancer in male infertility; (2) non-fatal stroke and endometrial cancer, and likely non-fatal coronary heart disease and ovarian cancer in polycystic ovary syndrome; (3) osteoporosis, psychosexual dysfunction, mood disorders and dementia in premature ovarian failure; (4) breast and ovarian cancer in carriers of BRCA1/2 mutations in diminished ovarian reserve; (5) clear cell and endometrioid histologic subtypes of invasive ovarian cancer, and likely low-grade serous invasive ovarian cancer, melanoma and non-Hodgkin lymphoma in endometriosis; and (6) endometrial and ovarian cancer in idiopathic infertility. The present data endorse the principle that the occurrence of a disease (in our case infertility) is non-random in the population and suggest that different infertility etiologies are genetically and clinically

  7. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    Directory of Open Access Journals (Sweden)

    Kampf Caroline

    2012-09-01

    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  8. GOUT: THE KING OF DISEASES AND THE DISEASE OF KINGS

    OpenAIRE

    Roberto Marcolongo

    2012-01-01

    Gout is a metabolic disorder caused by hyperuricemia resulting in joints and other tissues deposition of urate crystals. Clinical manifestation includes recurrent attacks of arthritis and accumulation of crystalline deposits called tophi. Gout is considered a progressive disease that, without long-term treatment, can progress to severe tophaceous gout. The disease is increasing in prevalence as a result of changes in diet, lifestyle and environmental factors. Hyperuricemia has a fundamental r...

  9. A systematic literature review of evidence-based clinical practice for rare diseases

    DEFF Research Database (Denmark)

    Rath, Ana; Salamon, Valérie; Peixoto, Sandra

    2017-01-01

    diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes....... CONCLUSIONS: Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic...

  10. Eosinophilic fasciitis in a military recruit: MRI evaluation with clinical correlation

    International Nuclear Information System (INIS)

    Liou, Chang-Hsien; Juan, Chun-Jung; Chen, Cheng-Yu.; Huang, Guo-Shu; Taylor, John A.M.; Gao, Hong-Wei

    2003-01-01

    Eosinophilic fasciitis (EF) is an uncommon connective tissue disease. We report a patient with EF who presented with episodic swelling and stiffness of his legs and forearms in combination with peripheral eosinophilia. Imaging studies of the legs and forearms, including computed tomography (CT) and magnetic resonance imaging (MRI), clearly demonstrated the characteristic finding of fascial thickening. The complete clinical imaging and pathological findings are described in this report. Cross-sectional imaging is useful in diagnosing EF and in the appropriate clinical scenario may be helpful in differentiating EF from other connective tissue diseases. (orig.)

  11. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January

  12. [Lyme disease--clinical manifestations and treatment].

    Science.gov (United States)

    Stock, Ingo

    2016-05-01

    Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

  13. Dynamic computed tomography findings in cerebrovascular diseases

    International Nuclear Information System (INIS)

    Araki, Yutaka; Tomoda, Kaname; Kariya, Mitsumasa; Mori, Shigeru; Mitomo, Masanori.

    1988-01-01

    Dynamic CT was performed with 41 patients with the clinically diagnosed cerebrovascular diseases. A visual evaluation based on the dynamic CT images classified six patterns of brain parenchymal enhancement, especially four patterns of which could only be detected by dynamic CT technique. Dynamic CT was proved of great value in detecting regional cerebral tissue filled by collaterals in retrograde fashion because of the occlusion of main arteries, namely brain tissue perfusion of internal carotid occlusion disease and moyamoya disease was best understood by dynamic CT with adequate resolution. (author)

  14. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  15. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat

  16. Evaluation of medication treatment for Alzheimer's disease on clinical evidence

    Directory of Open Access Journals (Sweden)

    Meng-qiu LI

    2014-03-01

    Full Text Available Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT, controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7, and 5 were low quality with score 3. It was summarized as follows: 1 Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine and an N-methyl-D-aspartate (NMDA receptor noncompetitive antagonist (memantine, are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2 Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009

  17. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    Science.gov (United States)

    Alberti, C

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

  18. Targeting diseased tissues by pHLIP insertion at low cell surface pH

    Directory of Open Access Journals (Sweden)

    Oleg A. Andreev

    2014-03-01

    Full Text Available The discovery of the pH Low Insertion Peptides (pHLIPs provides an opportunity to develop imaging and drug delivery agents targeting extracellular acidity. Extracellular acidity is associated with many pathological states, such as those in cancer, ischemic stroke, neurotrauma, infection, lacerations and others. The metabolism of cells in injured or diseased tissues often results in the acidification of the extracellular environment, so acidosis might be useful as a general marker for the imaging and treatment of diseased states if an effective targeting method can be developed. The molecular mechanism of a pHLIP peptide is based on pH-dependent membrane-associated folding. pHLIPs, being moderately hydrophobic peptides, have high affinities for cellular membranes at normal pH, but fold and insert across membranes at low pH, allowing them to sense pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we discuss the main principles of pHLIP interactions with membrane lipid bilayers at neutral and low pHs, the possibility of tuning the folding and insertion pH by peptide sequence variation, and potential applications of pHLIPs for imaging, therapy and image-guided interventions.

  19. Targeting diseased tissues by pHLIP insertion at low cell surface pH.

    Science.gov (United States)

    Andreev, Oleg A; Engelman, Donald M; Reshetnyak, Yana K

    2014-01-01

    The discovery of the pH Low Insertion Peptides (pHLIPs®) provides an opportunity to develop imaging and drug delivery agents targeting extracellular acidity. Extracellular acidity is associated with many pathological states, such as those in cancer, ischemic stroke, neurotrauma, infection, lacerations, and others. The metabolism of cells in injured or diseased tissues often results in the acidification of the extracellular environment, so acidosis might be useful as a general marker for the imaging and treatment of diseased states if an effective targeting method can be developed. The molecular mechanism of a pHLIP peptide is based on pH-dependent membrane-associated folding. pHLIPs, being moderately hydrophobic peptides, have high affinities for cellular membranes at normal pH, but fold and insert across membranes at low pH, allowing them to sense pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we discuss the main principles of pHLIP interactions with membrane lipid bilayers at neutral and low pHs, the possibility of tuning the folding and insertion pH by peptide sequence variation, and potential applications of pHLIPs for imaging, therapy and image-guided interventions.

  20. Barriers impeding serologic screening for celiac disease in clinically high-prevalence populations

    Science.gov (United States)

    2014-01-01

    Background Celiac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease. Methods 119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test. Results Two barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co

  1. Clinical investigation in Wilson's disease

    International Nuclear Information System (INIS)

    Mizutani, Naoki; Maehara, Mitsuo; Negoro, Tamiko; Watanabe, Kazuyoshi

    1983-01-01

    Wilson's disease of cerebral type with a chief complaint of tremor occurred in 3 brothers and sisters of a certain family line. Treatment with D-penicillamine produced remarkable clinical improvement as shown by the disappearance of tremor and Kayser-Fleischer ring. Cranial CT scans made before the treatment revealed abnormal findings such as low density areas in the (bilateral) thalamus and the lenticular nucleus, atrophy of the cerebral cortex, and enlargement of the ventricles. After the treatment, cranial CT revealed that the low density areas in the thalamus and the lenticular nucleus disappeared corresponding to the clinical improvement. However, the atrophy of the cerebral cortex and the enlargement of the ventricles were not ameliorated. (Ueda, J.)

  2. Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.

    Science.gov (United States)

    Tortelli, Rosanna; Seripa, Davide; Panza, Francesco; Solfrizzi, Vincenzo; Logroscino, Giancarlo

    2016-01-01

    Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted. The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification. © 2016 S. Karger AG, Basel.

  3. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

    Science.gov (United States)

    Takatsuki, Hanae; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Murayama, Shigeo; Atarashi, Ryuichiro; Nishida, Noriyuki; Satoh, Katsuya

    2016-10-01

    Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 10 6 /g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 10 6 /g SD50 did not exist the infectivity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Angiomatosis of bone and soft tissue: A spectrum of disease from diffuse lymphangiomatosis to vanishing bone disease in young patients

    International Nuclear Information System (INIS)

    Aviv, R.I.; McHugh, K.; Hunt, J.

    2001-01-01

    The application of cross-sectional imaging in the investigation of patients with angiomatosis reveals that lymphangiomatosis and vanishing bone disease should not be considered as separate entities, but rather as a spectrum of disease. We present a pictorial review of eight patients demonstrating the manifestations of soft tissue and bony involvement. We highlight a subgroup of patients with chyloid pleural effusions who have a poor prognosis. Aviv, R. I. et al. (2001)

  5. Infections Disease in the Dental Clinical Nigerian Dentists ...

    African Journals Online (AJOL)

    The dental clinic is a potential source of transmission of infectious disease due to the invasive nature of many dental procedures. Infectious disease therefore constitutes serious occupational hazards to all oral health care workers. This descriptive study aims to assess the knowledge of dentists on common transmissible ...

  6. Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design

    Directory of Open Access Journals (Sweden)

    Clare Selden

    2018-04-01

    Full Text Available Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.

  7. NON-COMMUNICABLE DISEASE PROGRAM IN AMPANGAN HEALTH CLINIC

    Directory of Open Access Journals (Sweden)

    MASTURA I

    2010-01-01

    Full Text Available Non-communicable diseases (NCDs represent among the most common and debilitating conditions seen in primary care. Patients’ care will often involves multiple providers and follow-up requires persistence by patients and clinicians alike, therefore ideal outcomes are often difficult to achieve. The need for better disease management policies and practice is growing. This is due to the changing demographic profile of the population, the increasing cost of managing people in acute care hospitals and the availability of new technologies and services. All these changes enable a different care paradigm which is more cost effective and provides people with chronic conditions an improved quality of life. Management of the NCDs therefore offers an excellent opportunity to practice chronic disease management - a systems approach designed to ensure excellent care. The NCD team has developed a comprehensive approach to chronic disease care. We would like to describe the NCD Program in Ampangan Health Clinic which represents many typical government health clinics in Malaysia and the processes by which it was developed. Included are specific examples of the tools and how they can be used by individual clinicians incaring for patients. The integration of Chronic Disease Management Services into health care systems is the direction being undertaken to tackle the burden of chronic disease. Disease management supports the shift in healthcare from an emphasis on managing the acute episode to managing the entire disease course, highlighting both prevention and maintenance of wellbeing for patients with chronic diseases. Disease management promotes better integration and coordination of care across all aspects of the health sector.

  8. Clinical application of 1H-chemical-shift imaging (CSI) to brain diseases

    International Nuclear Information System (INIS)

    Naruse, Shoji; Furuya, Seiichi; Ide, Mariko

    1992-01-01

    An H-1 chemical shift imaging (CSI) was developed as part of the clinical MRI system, by which magnetic resonance spectra (MRS) can be obtained from multiple small voxels and metabolite distribution in the brain can be visualized. The present study was to determine the feasibility and clinical potential of using an H-1 CSI. The device used was a Magnetom H 15 apparatus. The study population was comprised of 25 healthy subjects, 20 patients with brain tumor, 4 with ischemic disease, and 6 with miscellaneous degenerative disease. The H-1 CSI was obtained by the 3-dimensional Fourier transformation. After suppressing the lipid signal by the inversion-recovery method and the water signal by the chemical-shift selective pulse with a following dephasing gradient, 2-directional 16 x 16 phase encodings were applied to the 16 x 16∼18 x 18 cm field of view, in which a 8 x 8 x 2∼10 x 10 x 2 cm area was selected by the stimulated echo or spin-echo method. The metabolite mapping and its contour mapping were created by using the curve-fitted area, with interpolation to the 256 x 256 matrix. In the healthy group, high resolution spectra for N-acetyl aspartate (NAA), creatine, choline (Cho), and glutamine/glutamate were obtained from each voxel; and metabolite mapping and contour mapping also clearly showed metabolite distribution in the brain. In the group of brain tumor, an increased Cho and lactate and loss of NAA were observed, along with heterogeneity within the tumor and changes in the surrounding tissue; and there was a good correlation between lactate peak and tumor malignancy. The group of ischemic and degenerative disease had a decreased NAA and increased lactate on both spectra and metabolite mapping, depending on disease stage. These findings indicated that H-1 CSI is helpful for detecting spectra over the whole brain, as well as for determining metabolite distribution. (N.K.)

  9. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    International Nuclear Information System (INIS)

    Ahlawat, Shivani; Fayad, Laura M.

    2018-01-01

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  10. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Shivani [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Fayad, Laura M. [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Oncology, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Orthopaedic Surgery, Baltimore, MD (United States)

    2018-03-15

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  11. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

    Science.gov (United States)

    Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K.; Zhao, Hongyu

    2017-01-01

    Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer’s disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson’s disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:28742084

  12. Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen.

    Science.gov (United States)

    Latella, G; Cocco, A; Angelucci, E; Viscido, A; Bacci, S; Necozione, S; Caprilli, R

    2009-04-01

    The severity of clinical activity of Crohn's disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn's disease first diagnosed at surgery has never been investigated. To assess the clinical course of Crohn's disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. Hospital clinical records of 490 consecutive Crohn's disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. Kaplan-Meier survival method and Cox proportional hazards regression model. Of the 490 Crohn's disease patients, 115 had diagnosis of Crohn's disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test pacute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn's disease, at least in the subset of patients with ileal and complicated disease.

  13. Clinical applications of radioiodine 131 (I131) in the thyroid diseases

    International Nuclear Information System (INIS)

    Gonzalez Rivero, Levi; Turcios Trista, Silvia Elena; Velasco Mirabal, Milagros

    2012-01-01

    Radioiodine 131 is a radioactive isotope that is successfully used for the diagnosis and the treatment of benign and malignant thyroid diseases. Its quality of selectively integrating to the thyroid metabolism and emitting a signal allows it to describe the gland functioning through capture studies, and to delimit the morphology and location of the tissues that capture iodine by means of scintigraphy. It is also a simple, safe and cost-effective radiotherapy used as first-line therapeutics in the control of hyperthyroidism. The dose and right time of application should be individualized according to the etiology and the clinic of each patient. Radioiodine 131 offers an efficient alternative to reduce the size of non-toxic goiter in addition to supporting the surgical treatment of the differentiated thyroid carcinoma and destroying with ablative doses the tissular remains and the metastatic lesions that can be detected during the gammagraphic follow-up. Radioiodine 131 depends on the fulfillment of safety regulations against radioactivity

  14. Clinical applications of radioiodine 131 (I131) in the thyroid diseases

    International Nuclear Information System (INIS)

    Gonzalez, Rivero Levi; Turcios Trista, Silvia Elena; Velasco Mirabal, Milagros

    2012-01-01

    Radioiodine 131 is a radioactive isotope that is successfully used for the diagnosis and the treatment of benign and malignant thyroid diseases. Its quality of selectively integrating to the thyroid metabolism and emitting a signal allows it to describe the gland functioning through capture studies, and to delimit the morphology and location of the tissues that capture iodine by means of gammagraphy. It is also a simple, safe and cost-effective radiotherapy used as first-line therapeutics in the control of hyperthyroidism. The dose and right time of application should be individualized according to the etiology and the clinic of each patient. Radioiodine 131 offers an efficient alternative to reduce the size of non-toxic goiter in addition to supporting the surgical treatment of the differentiated thyroid carcinoma and destroying with ablative doses the tissular remains and the metastatic lesions that can be detected during the gammagraphic follow-up. Radioiodine 131 depends on the fulfillment of safety regulations against radioactivity

  15. Study on clinical symptoms in canine cardiac diseases

    Directory of Open Access Journals (Sweden)

    F. Karlette Anne

    Full Text Available Cardiac diseases in canines are an extensively studied phenomenon all over the world but meagre information has been reported in India. Certain problems, including historical, physical, and laboratory abnormalities, are associated with cardiovascular or pulmonary disease. In India however, the recognition of canine cardiac diseases has been delayed, and ignored on account of lack of awareness and knowledge by the owner and inadequate diagnostic facility to a field veterinarian. Considering the above facts, the present study was undertaken in Gujarat to survey the prevalence of common cardiac diseases in hospital population of dogs along with the clinical symptoms which often goes undetected due to lack of proper diagnostic techniques to be implied and the most forms of heart disease may be present for many years before any evidence of failure develops. In the present study most of the clinical cases of cardiac diseases were presented with a history of nocturnal coughing (seven cases; 2.55%, exercise intolerance (five cases; 1.82%, partial or complete anorexia (five cases; 1.82%, swelling in abdominal area (four cases; 1.45%, dullness and depression (two cases; 0.72%, cachexia and hepatojugular pulsation (one case each; 0.36% each at times. [Vet World 2009; 2(8.000: 307-309

  16. Lung involvement in systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  17. Are mast cells instrumental for fibrotic diseases?

    Directory of Open Access Journals (Sweden)

    Catherine eOvered-Sayer

    2014-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a fatal lung disorder of unknown etiology characterised by accumulation of lung fibroblasts and extracellular matrix deposition, ultimately leading to compromised tissue architecture and lung function capacity. IPF has a heterogeneous clinical course; however the median survival after diagnosis is only 3-5 years. The pharmaceutical and biotechnology industry has made many attempts to find effective treatments for IPF, but the disease has so far defied all attempts at therapeutic intervention. Clinical trial failures may arise for many reasons, including disease heterogeneity, lack of readily measurable clinical end points other than overall survival, and, perhaps most of all, a lack of understanding of the underlying molecular mechanisms of the progression of IPF.The precise link between inflammation and fibrosis remains unclear, but it appears that immune cells can promote fibrosis by releasing fibrogenic factors. So far, however, therapeutic approaches targeting macrophages, neutrophils, or lymphocytes have failed to alter disease pathogenesis. A new cell to garner research interest in fibrosis is the mast cell. Increased numbers of mast cells have long been known to be present in pulmonary fibrosis and clinically correlations between mast cells and fibrosis have been reported. More recent data suggests that mast cells may contribute to the fibrotic process by stimulating fibroblasts resident in the lung, thus driving the pathogenesis of the disease. In this review, we will discuss the mast cell and its physiological role in tissue repair and remodelling, as well as its pathological role in fibrotic diseases such as IPF, where the process of tissue repair and remodelling is thought to be dysregulated.

  18. Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

    Science.gov (United States)

    Spies, Petra E; Verbeek, Marcel M; Sjogren, Magnus J C; de Leeuw, Frank-Erik; Claassen, Jurgen A H R

    2014-01-01

    Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. The AD biomarkers CSF amyloid β42, amyloid β40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. No association between CSF amyloid β42, amyloid β40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

  19. Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

    Science.gov (United States)

    Lowenthal, Justin; Gerecht, Sharon

    2016-05-06

    Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Bioimaging of teeth and their surrounding tissues and biofilm

    DEFF Research Database (Denmark)

    Dige, Irene; Spin-Neto, Rubens; Kraft, David Christian Evar

    At the Department of Dentistry and Oral Health, bioimaging is a central part of our research of dental tissues and diseases in the oral cavity. We conduct research in the understanding, preventing, and treating of such diseases and there has been a strategic focus on the image-based investigation...... of clinical problems. For example, because of the etiological role of biofilms in many diseases including dental caries and periodontitis, we have investigated biofilm ecology combining newer molecular techniques such as Confocal Laser Scanning Microscopy (CLSM) and fluorescence techniques. These methods...

  1. Prediction of treatment response and metastatic disease in soft tissue sarcoma

    Science.gov (United States)

    Farhidzadeh, Hamidreza; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Raghavan, Meera.; Gatenby, Robert A.

    2014-03-01

    Soft tissue sarcomas (STS) are a heterogenous group of malignant tumors comprised of more than 50 histologic subtypes. Based on spatial variations of the tumor, predictions of the development of necrosis in response to therapy as well as eventual progression to metastatic disease are made. Optimization of treatment, as well as management of therapy-related side effects, may be improved using progression information earlier in the course of therapy. Multimodality pre- and post-gadolinium enhanced magnetic resonance images (MRI) were taken before and after treatment for 30 patients. Regional variations in the tumor bed were measured quantitatively. The voxel values from the tumor region were used as features and a fuzzy clustering algorithm was used to segment the tumor into three spatial regions. The regions were given labels of high, intermediate and low based on the average signal intensity of pixels from the post-contrast T1 modality. These spatially distinct regions were viewed as essential meta-features to predict the response of the tumor to therapy based on necrosis (dead tissue in tumor bed) and metastatic disease (spread of tumor to sites other than primary). The best feature was the difference in the number of pixels in the highest intensity regions of tumors before and after treatment. This enabled prediction of patients with metastatic disease and lack of positive treatment response (i.e. less necrosis). The best accuracy, 73.33%, was achieved by a Support Vector Machine in a leave-one-out cross validation on 30 cases predicting necrosis treatment and metastasis.

  2. The influence of smoking on clinical periodontal disease

    Directory of Open Access Journals (Sweden)

    Ina Hendiani

    2009-07-01

    Full Text Available Periodontal disease has very complex and multi factor etiology. Plaque bacteria is the main cause of periodontal disease and another risk factor that also plays a role is a smoking habit. Cigarette product such as nicotine can influence the development of periodontal disease that can directly and systemically damage the function of PMN cell. The research was conducted by taking a clinical examination on the smoking influence that covers the number of cigarettes and the period of smoking, and kind of cigarette to the worse of periodontal disease, and by measuring the epithelial attachment loss and the bleeding index. The research was conducted to 152 male aged 20-45 years old, comprised 80 smokers and 72 nonsmokers at the Clinic of Faculty of Dentistry Universitas Indonesia, Jakarta. The result of the research showed that smoking gave influence on the worse of the periodontal disease. There was a profound relationship between the smoking period and the number of cigarettes consumed everyday indicated by the epithelial attachment loss. Smoking did not enhance gingival bleeding. The relationship between kinds of cigarette and the gingival bleeding score and the epithelial attachment loss did not show a significant bleeding.

  3. Advances in clinical application of optical coherence tomography in vitreomacular interface disease

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    Xiao-Li Xing

    2013-08-01

    Full Text Available Vitreous macular interface disease mainly includes vitreomacular traction syndrome, idiopathic macular epiretinal membrane and idiopathic macular hole. Optical coherence tomography(OCTas a new tool that provides high resolution biopsy cross section image non traumatic imaging inspection, has a unique high resolution, no damage characteristics, and hence clinical widely used, vitreous macular interface for clinical disease diagnosis, differential diagnosis and condition monitoring and quantitative evaluation, treatment options, etc provides important information and reference value. Vitreous macular interface disease in OCT image of anatomical morphology characteristics, improve the clinical on disease occurrence and development of knowledge. We reviewed the advances in the application of OCT in vitreomacular interface disease.

  4. Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

    Science.gov (United States)

    Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

    2015-12-01

    Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.

  5. Fluid biomarkers in clinical trials of Alzheimer’s disease therapeutics

    Directory of Open Access Journals (Sweden)

    Aaron eRitter

    2015-08-01

    Full Text Available With the demographic shift of the global population towards longer life expectancy, the number of people living with Alzheimer’s disease (AD has rapidly expanded and is projected to triple by the year 2050. Current treatments provide symptomatic relief but do not affect the underlying pathology of the disease. Therapies that prevent or slow the progression of the disease are urgently needed to avoid this growing public health emergency. Insights gained from decades of research have begun to unlock the pathophysiology of this complex disease and have provided targets for disease modifying therapies. In the last decade, few therapeutic agents designed to modify the underlying disease process have progressed to clinical trials and none have been brought to market. With the focus on disease modification, biomarkers promise to play an increasingly important role in clinical trials. Six biomarkers have now been included in diagnostic criteria for AD and are regularly incorporated into clinical trials. Three biomarkers are neuroimaging measures—hippocampal atrophy measured by magnetic resonance imaging (MRI, amyloid uptake as measured by Pittsburg compound B positron emission tomography (PiB PET, and decreased fluorodeoxyglucose (18F uptake as measured by positron emission tomography (FDG PET—and three are sampled from fluid sources—cerebrospinal fluid (CSF levels

  6. Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

    2017-07-01

    Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  7. Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

    Science.gov (United States)

    Li, Li; Xie, Wengming; Li, Hui

    2012-12-01

    The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

  8. Recent clinical trials in valvular heart disease.

    Science.gov (United States)

    Kiss, Daniel; Anwaruddin, Saif

    2017-07-01

    With widespread adoption of transcatheter aortic valve replacement, there has been a change in the approach to management of valvular heart disease. New interest has taken hold in transcatheter therapies for valvular heart disease, as well as research into pathophysiology and progression of disease. Additionally, several key trials have further refined our understanding of surgical management of valvular heart disease. This review will elucidate recent clinical trial data leading to changes in practice. There have been several landmark trials expanding the indications for transcatheter aortic valve replacement. Additionally, although still early, trials are beginning to demonstrate the feasibility and safety of transcatheter mitral valves. Options for transcatheter management of right-sided valvular disease continue to evolve, and these are areas of active investigation. The emergence of novel therapies for valvular heart disease has expanded the management options available, allowing physicians to better individualize treatment of patients with valvular heart disease. This review will focus on the recent (within 2 years) trials in this field of interest.

  9. Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Sofia Dias

    2018-01-01

    Full Text Available Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

  10. Use of cross-linked carboxymethyl cellulose for soft-tissue augmentation: preliminary clinical studies

    Directory of Open Access Journals (Sweden)

    Mauro Leonardis

    2010-11-01

    Full Text Available Mauro Leonardis1, Andrea Palange2, Rodrigo FV Dornelles3, Felipe Hund41Department of Plastic Surgery, Salvator Mundi International Hospital, Roma, Italy; 2Department of Aesthetic Medicine, Fisiobios, Roma, Italy; 3Department of Plastic Surgery, Núcleo de Plástica Avançada, São Paulo, SP, Brazil; 4Department of Plastic Surgery, Consultorio de Cirurgia Plastica, Criciuma, SC, BrazilPurpose: The continual search for new products for soft-tissue augmentation has in recent years led to the introduction of long lasting alternatives to hyaluronic acids and collagen that are composed of other polymers able to improve clinical persistence over time. This is the first report in which sodium carboxymethyl cellulose (CMC has been chemically treated by the cross-linking process and thus used as a hydrogel for soft-tissue augmentation through injection with thin needles. The study evaluates, from a clinical point of view, the behavior of cross-linked carboxymethyl cellulose hydrogel used in the aesthetic field and its side effects so as to check the safety and performance of the polymer following intradermal injections.Patients and methods: This work shows the preliminary results of an ongoing clinical study conducted between 2006 and 2009, performed on 84 healthy volunteers (62 females, 22 males aged between 18 and 72 years, for the treatment of 168 nasolabial folds, 45 perioral wrinkles, and 39 lip volume.Results: Study results show an excellent correction of facial defects. Tolerance and aesthetic quality of the correction obtained indicate considerable safety features and absence of side effects. From a clinical point of view, hydrogel is gradually absorbed into the injection site without migration issues.Conclusion: Cross-linked CMC hydrogel proves to be an ideal agent for soft tissue augmentation with regard to safety and ease of application. It did not cause infection, extrusion, migration, or adverse reactions in the patients who have been

  11. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Gimpel, Charlotte; Pohl, Martin [Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Center for Pediatrics, Freiburg (Germany); Jung, Bernd A. [Inselspital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Jung, Sabine [Medical Center - University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Brado, Johannes; Odening, Katja E. [University Heart Center Freiburg, Department of Cardiology and Angiology I, Freiburg (Germany); Schwendinger, Daniel [University Children' s Hospital Zurich, Zurich (Switzerland); Burkhardt, Barbara [University Children' s Hospital Zurich, Pediatric Heart Center, Zurich (Switzerland); Geiger, Julia [University Children' s Hospital Zurich, Department of Radiology, Zurich (Switzerland); Northwestern University, Department of Radiology, Chicago, IL (United States); Arnold, Raoul [University Hospital Heidelberg, Department of Pediatric and Congenital Cardiology, Heidelberg (Germany)

    2017-02-15

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V{sub E}), late diastolic (V{sub A}) and peak systolic (V{sub S}) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz{sub base} -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz{sub mid} -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz{sub apex} -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr{sub base} -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr{sub mid} -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr{sub apex} -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  12. Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

    Science.gov (United States)

    Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

    1996-01-01

    OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

  13. Current clinical research of immunoglobulin G4-related orbital disease

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-05-01

    Full Text Available Immunoglobulin G4-related disease(IgG4-related diseasehas received lots of attention in medical community as a recently recognized fibro-inflammatory condition. It is characterized by infiltration of IgG4-immunopositive plasmacytes and concentration of elevated serum IgG4. IgG4-related disease shows organ enlargement or nodular/hyperplastic lesions in various organs including the pancreas, hepatobiliary tract and orbit, which is called IgG4-related orbital disease. The diagnostic criteria for IgG4-related disease and IgG4-related orbital disease has recently been established, which is based on clinical, imaging and histopathologic features of the orbital lesions. Besides, attention should be drawn to the differentiation from other diseases. The treatment is empirical including corticosteroids, immunosuppressive drugs, radiotherapy, and rituximab. This article reviews clinical progression of IgG4-related orbital disease.

  14. Norrie disease: extraocular clinical manifestations in 56 patients.

    Science.gov (United States)

    Smith, Sharon E; Mullen, Thomas E; Graham, Dionne; Sims, Katherine B; Rehm, Heidi L

    2012-08-01

    Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. Copyright © 2012 Wiley Periodicals, Inc.

  15. Generalized connective tissue disease in Crtap-/- mouse.

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    Dustin Baldridge

    2010-05-01

    Full Text Available Mutations in CRTAP (coding for cartilage-associated protein, LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1] or PPIB (coding for Cyclophilin B [CYPB] cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in alpha1(I and alpha1(II chains, there was also loss of 3Hyp at proline 986 in alpha2(V chains. In contrast, at two of the known 3Hyp sites in alpha1(IV chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin.

  16. Recommendations for obstetric management and principles of cooperation between rheumatologists and obstetricians in systemic connective tissue disease patients

    Directory of Open Access Journals (Sweden)

    Justyna Teliga-Czajkowska

    2014-03-01

    Full Text Available Systemic connective tissue diseases, notably rheumatoid arthritis and systemic lupus erythematosus, frequently affect women of reproductive age. The significant impact of the diseases on the course of pregnancy is well established, and vice versa – the course of systemic connective tissue diseases may be affected by pregnancy. The risk of developing serious pregnancy complications and obstetric failures is markedly higher in the mentioned disease group. The foundation of obstetric success, i.e. giving birth to a healthy child and pregnancy having no effect on the course of a given autoimmune disease, is cooperation between rheumatologists and obstetricians so as to plan procreation at an optimal period and provide accurate pregnancy monitoring. The article delineates recommendations relating to contraception management, obstetric supervision and fetus wellbeing monitoring, from the point of view of the obstetrician.

  17. Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

    Science.gov (United States)

    Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

    2011-09-01

    Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

  18. Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

    Science.gov (United States)

    González García, A; Patier de la Peña, J L; Ortego Centeno, N

    2017-03-01

    Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  19. Bilingualism delays clinical manifestation of Alzheimer's disease

    OpenAIRE

    Woumans, Evy; Santens, Patrick; Sieben, Anne; Versijpt, Jan; Stevens, Michaël; Duyck, Wouter

    2015-01-01

    The current study investigated the effects of bilingualism on the clinical manifestation of Alzheimer's disease (AD) in a European sample of patients. We assessed all incoming AD patients in two university hospitals within a specified timeframe. Sixty-nine monolinguals and 65 bilinguals diagnosed with probable AD were compared for time of clinical AD manifestation and diagnosis. The influence of other potentially interacting variables was also examined. Results indicated a significant delay f...

  20. Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

    Directory of Open Access Journals (Sweden)

    Stemer Gunar

    2011-07-01

    Full Text Available Abstract Background Chronic kidney disease (CKD and end-stage renal disease (ESRD represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations. Methods A literature search was conducted using the Medline, Embase and International Pharmaceutical Abstracts databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems. Results Among a total of 21 studies, only four (19% were controlled trials. The majority of studies were descriptive (67% and before-after studies (14%. Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional

  1. miRNAs in inflammatory skin diseases and their clinical implications

    DEFF Research Database (Denmark)

    Løvendorf, Marianne B; Skov, Lone

    2015-01-01

    biological processes. The clinical implications of miRNAs are intriguing, both from a diagnostic and a therapeutic perspective. Accordingly, there is emerging evidence for the clinical potential of miRNAs as both biomarkers and possible therapeutic targets in skin diseases. Future studies will hopefully...... incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental...

  2. Measurement of tissue viscoelasticity with ultrasound

    Science.gov (United States)

    Greenleaf, J. F.; Alizad, A.

    2017-02-01

    Tissue properties such as elasticity and viscosity have been shown to be related to such tissue conditions as contraction, edema, fibrosis, and fat content among others. Magnetic Resonance Elastography has shown outstanding ability to measure the elasticity and in some cases the viscosity of tissues, especially in the liver, providing the ability to stage fibrotic liver disease similarly to biopsy. We discuss ultrasound methods of measuring elasticity and viscosity in tissues. Many of these methods are becoming widely available in the extant ultrasound machines distributed throughout the world. Some of the methods to be discussed are in the developmental stage. The advantages of the ultrasound methods are that the imaging instruments are widely available and that many of the viscoelastic measurements can be made during a short addition to the normal ultrasound examination time. In addition, the measurements can be made by ultrasound repetitively and quickly allowing evaluation of dynamic physiologic function in circumstances such as muscle contraction or artery relaxation. Measurement of viscoelastic tissue mechanical properties will become a consistent part of clinical ultrasound examinations in our opinion.

  3. MDS clinical diagnostic criteria for Parkinson's disease in China.

    Science.gov (United States)

    Li, Jun; Jin, Miao; Wang, Li; Qin, Bin; Wang, Kang

    2017-03-01

    The Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD Criteria) was introduced by the Movement Disorder Society in 2015 for research purposes. However, its use for clinical diagnosis of Parkinson disease still needs further revision. This study compares the UK-Criteria versus MDS-PD Criteria in the clinical diagnosis of Parkinson disease referred to the China-Japan Friendship Hospital of Beijing, China. To compare the MDS-PD Criteria with the UK-Criteria and discuss the feasibility of the clinical application of MDS-PD Criteria as a general guide to clinical diagnosis of PD in Chinese PD patients. 150 patients of neurology clinic of China-Japan Friendship Hospital of Beijing were recruited in our research. They were divided into three groups: UK-Criteria group, MDS-PD Criteria group and a combined group of UK and MDS-PD Criteria. Clinical history was collected while physical and auxiliary examinations were done by a trained neurologist according to the corresponding criteria. An interrater reliability analysis using the Kappa statistic claimed substantial agreement (κ = 0.626) between the MDS-PD Criteria and the UK-Criteria. The differences between the diagnostic results of these two criteria were statistically significant by paired Chi-square test (p = 0.000). It was found that levodopa-induced dyskinesia had a good positive predictive value, while early bulbar impairment and inspiratory dysfunction presented a negative predictive value. The MDS-PD Criteria emphasize the importance of non-motor symptoms, keeping the motor symptoms as the core for the clinical diagnosis of PD, and establish categories of diagnosis features and levels of certainty which are more complete and organized to be used and replicated by non specialized physicians to evaluated patients with Parkinsonism. The higher sensitivity of MDS-PD Criteria compared with UK-Criteria is worth being widely used in clinical work.

  4. Treatment of Mucosa-associated Lymphoid Tissue Lymphoma in Sjogren's Syndrome : A Retrospective Clinical Study

    NARCIS (Netherlands)

    Pollard, Rodney P. E.; Pijpe, Justin; Bootsma, Hendrika; Spijkervet, Fred K. L.; Kluin, Philip M.; Roodenburg, Jan L. N.; Kallenberg, Cees G. M.; Vissink, Arjan; van Imhoff, Gustaaf W.

    2011-01-01

    Objective. To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjogren's syndrome (SS). Methods. All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical

  5. A Review of the Centers for Disease Control and Prevention's Guidelines for the Clinical Laboratory Diagnosis of Lyme Disease.

    Science.gov (United States)

    Miraglia, Caterina M

    2016-12-01

    The purpose of this paper is to review information regarding the current guidelines for the clinical laboratory diagnosis of Lyme disease as set forth by the Centers for Disease Control and Prevention (CDC) to chiropractic physicians and to discuss the clinical utility of this testing. The CDC's website was reviewed to determine what their current recommendations are for the clinical laboratory testing of Lyme disease. The CDC's established guidelines recommend the use of a 2-tiered serologic testing algorithm for the evaluation of patients with suspected Lyme disease. This review provides doctors of chiropractic with information to remain current with the CDC's recommended guidelines for Lyme disease testing because patients may present to their office with the associated signs and symptoms of Lyme disease.

  6. Mitochondrial disease patient motivations and barriers to participate in clinical trials.

    Directory of Open Access Journals (Sweden)

    Zarazuela Zolkipli-Cunningham

    Full Text Available Clinical treatment trials are increasingly being designed in primary mitochondrial disease (PMD, a phenotypically and genetically heterogeneous collection of inherited multi- system energy deficiency disorders that lack effective therapy. We sought to identify motivating factors and barriers to clinical trial participation in PMD.A survey study was conducted in two independent mitochondrial disease subject cohorts. A discovery cohort invited subjects with well-defined biochemical or molecularly- confirmed PMD followed at a single medical center (CHOP, n = 30/67 (45% respondents. A replication cohort included self-identified PMD subjects in the Rare Disease Clinical Research Network (RDCRN national contact registry (n = 290/1119 (26% respondents. Five-point Likert scale responses were analyzed using descriptive and quantitative statistics. Experienced and prioritized symptoms for trial participation, and patient attitudes toward detailed aspects of clinical trial drug features and study design.PMD subjects experienced an average of 16 symptoms. Muscle weakness, chronic fatigue, and exercise intolerance were the lead symptoms encouraging trial participation. Motivating trial design factors included a self-administered study drug; vitamin, antioxidant, natural or plant-derivative; pills; daily treatment; guaranteed treatment access during and after study; short travel distances; and late-stage (phase 3 participation. Relative trial participation barriers included a new study drug; discontinuation of current medications; disease progression; daily phlebotomy; and requiring participant payment. Treatment trial type or design preferences were not influenced by population age (pediatric versus adult, prior research trial experience, or disease severity.These data are the first to convey clear PMD subject preferences and priorities to enable improved clinical treatment trial design that cuts across the complex diversity of disease. Partnering with rare

  7. Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, H; Olesen, J

    2001-01-01

    , brain and connective tissue, and more recently it has been used in the clinical setting to assess circulatory and metabolic abnormalities. Quantitative measures of blood flow are also possible using NIRS and a light-absorbing tracer, which can be applied to evaluate circulatory responses to exercise......Near infrared spectroscopy (NIRS) is becoming a widely used research instrument to measure tissue oxygen (O2) status non-invasively. Continuous-wave spectrometers are the most commonly used devices, which provide semi-quantitative changes in oxygenated and deoxygenated hemoglobin in small blood...... vessels (arterioles, capillaries and venules). Refinement of NIRS hardware and the algorithms used to deconvolute the light absorption signal have improved the resolution and validity of cytochrome oxidase measurements. NIRS has been applied to measure oxygenation in a variety of tissues including muscle...

  8. Periodontal disease in diabetic patients - clinical and histopathological aspects.

    Science.gov (United States)

    Corlan Puşcu, Dorina; Ciuluvică, Radu Constantin; Anghel, Andreea; Mălăescu, Gheorghe Dan; Ciursaş, Adina Nicoleta; Popa, Gabriel Valeriu; Agop Forna, Doriana; Busuioc, Cristina Jana; Siloşi, Izabela

    2016-01-01

    Periodontal disease is one of the most frequent diseases affecting people all over the world. The relation between periodontal disease and diabetes mellitus raised the interest both of dentists and doctors treating metabolic diseases, as the two conditions influence one another. In our study, we analyzed a number of 75 patients with diabetes mellitus and periodontal disease that presented to the medical consultory for conditions of the dental maxillary system. The clinical study showed that periodontal disease and diabetes may affect young adults as well, still this pathological association more frequently appears after the age of 50. The disease was identified especially in the women living in urban area. The clinical examination of the dental maxillary system identified the presence of gingival ulcerations, dental calculus, gingival bleeding, radicular leftovers with anfractuous margins, fixed prostheses with an inappropriate cervical adjustment. Of the systemic diseases associated to periodontal disease and diabetes mellitus, there was observed that 66.66% of the patients also suffered from cardiovascular diseases (high blood pressure, ischemic cardiopathy, heart failure), and 37.33% suffered from obesity. The histopathological and immunohistochemical tests highlighted the presence of an inflammatory chronic, intense reaction, mainly formed of lymphocytes, plasmocytes, macrophages and granulocytes, heterogeneously disseminated and alteration of the structure of marginal and superficial periodontium. The inflammatory reaction in the patients with periodontal disease and diabetes was more intense than in the patients with periodontal disease without diabetes.

  9. Effects of bleomycin and x irradiation on the frequency of chromosomal aberrations in selected connective tissue diseases

    International Nuclear Information System (INIS)

    Burkhardt, W.C. Jr.

    1978-01-01

    Whole blood lymphocytes from 28 patients with selected connective tissue disorders (6 progressive systemic sclerosis (PSS), 6 anti-nuclear antibody positive rheumatoid arthritis, 6 anti-nuclear antibody negative rheumatoid arthritis, 6 systemic lupus erythematosus, and 4 mixed connective tissue disease) and 17 controls matched for sex, age, and race were studied to determine the frequency of spontaneous as well as bleomycin and/or x-irradiation induced chromosomal aberrations. The effects of bleomycin on cultured lymphocytes were tested, but differential susceptibilities to this clastogen were not demonstrated among the disease groups and controls investigated. However, the combined effect of bleomycin and x irradiation were found to be additive in control lymphocytes, nearly additive in PSS, RA+, and SLE cultures, but reduced considerably from the expected additive value in Ra- cultures. This study indicated that peripheral blood lymphocytes from patients with connective tissue disease, as a whole, possess greater frequencies of spontaneous chromosomal aberrations than matched controls and that x rays can produce greater frequencies of chromosomal aberrations in whole blood lymphocytes of PSS patients than in suitably matched control individuals

  10. Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review.

    Science.gov (United States)

    Miron, Richard J; Fujioka-Kobayashi, Masako; Bishara, Mark; Zhang, Yufeng; Hernandez, Maria; Choukroun, Joseph

    2017-02-01

    The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and dentistry.

  11. Clinic Attendance of Youth With Sickle Cell Disease on Hydroxyurea Treatment.

    Science.gov (United States)

    Ingerski, Lisa M; Arnold, Trisha L; Banks, Gabrielle; Porter, Jerlym S; Wang, Winfred C

    2017-07-01

    The objective of this study is to describe rates of clinic attendance of youth with sickle cell disease prescribed hydroxyurea and examine potential demographic and medical factors related to consistent clinic attendance. Participants included 148 youth diagnosed with sickle cell disease and prescribed hydroxyurea during a single calendar year. Clinic attendance and potential demographic and medical factors related to attendance were extracted via systematic retrospective medical chart review. Youth attended 90.3% of scheduled appointments and 85.1% of youth attended at least 80% of scheduled clinic appointments during the study window. Adjusting for other factors, multivariate analysis revealed families with fewer children in the household, families with private insurance, youth experiencing fever, and youth not experiencing pain during the calendar year were more likely to consistently attend clinic visits. Adherence to clinic appointments is critical to optimizing health outcomes for youth with sickle cell disease and integral for adequate monitoring of youth prescribed hydroxyurea, in particular. Findings may aid providers in appropriately identifying possible barriers to clinic attendance to develop attendance promotion interventions.

  12. Imaging tissue hypoxia: clinical and pre-clinical experience with {sup 123}IAZA

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, L.I. [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research, Faculty of Pharmacy and Pharmaceutical Sciences

    1997-10-01

    The molecular mechanisms that underline the selective binding of iodazomycin arabinoside, IAZA, and related nitromidazoles are reviewed as a basis for interpretation of preclinical and clinical data for hypoxic binding of radioiodinated IAZA. Clinical data are presented for {sup 123}IAZA uptake in a number of pathologies including metastatic tumours, peripheral vascular disease in diabetes, muscle stress and rheumatoid arthritis. The results of studies to determine the influence of tumour type on uptake of {sup 123} I-IAZA in patients with a variety of deep-seated solid tumours will be presented. Correlations of hypoxia-dependent binding with {sup 99m}Tc-HMPAO perfusion images will be reviewed and early correlations of uptake to treatment response in cancer will be presented. Unusual features of {sup 123}I-IAZA biodistribution will also be discussed together with detailed pharmacokinetic and radiation dosimetry data for `2{sup 123}I- IAZA in normal volunteers 27 refs., 1 fig.

  13. Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Repeke

    2012-02-01

    Full Text Available Periodontitis comprises a group of multifactorial diseases in which periodontopathogens accumulate in dental plaque and trigger host chronic inflammatory and immune responses against periodontal structures, which are determinant to the disease outcome. Although unusual cases of non-inflammatory destructive periodontal disease (NIDPD are described, their pathogenesis remains unknown. A unique NIDPD case was investigated by clinical, microbiological, immunological and genetic tools. The patient, a non-smoking dental surgeon with excessive oral hygiene practice, presented a generalized bone resorption and tooth mobility, but not gingival inflammation or occlusion problems. No hematological, immunological or endocrine alterations were found. No periodontopathogens (A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola or viruses (HCMV, EBV-1 and HSV-1 were detected, along with levels of IL-1β and TNF-a in GCF compatible with healthy tissues. Conversely ALP, ACP and RANKL GCF levels were similar to diseased periodontal sites. Genetic investigation demonstrated that the patient carried some SNPs, as well HLA-DR4 (*0404 and HLA-B27 alleles, considered risk factors for bone loss. Then, a less vigorous and diminished frequency of toothbrushing was recommended to the patient, resulting in the arrest of alveolar bone loss, associated with the return of ALP, ACP and RANKL in GCF to normality levels. In conclusion, the unusual case presented here is compatible with the previous description of NIDPD, and the results that a possible combination of excessive force and frequency of mechanical stimulation with a potentially bone loss prone genotype could result in the alveolar bone loss seen in NIDPD.

  14. Classification of coronary artery tissues using optical coherence tomography imaging in Kawasaki disease

    Science.gov (United States)

    Abdolmanafi, Atefeh; Prasad, Arpan Suravi; Duong, Luc; Dahdah, Nagib

    2016-03-01

    Intravascular imaging modalities, such as Optical Coherence Tomography (OCT) allow nowadays improving diagnosis, treatment, follow-up, and even prevention of coronary artery disease in the adult. OCT has been recently used in children following Kawasaki disease (KD), the most prevalent acquired coronary artery disease during childhood with devastating complications. The assessment of coronary artery layers with OCT and early detection of coronary sequelae secondary to KD is a promising tool for preventing myocardial infarction in this population. More importantly, OCT is promising for tissue quantification of the inner vessel wall, including neo intima luminal myofibroblast proliferation, calcification, and fibrous scar deposits. The goal of this study is to classify the coronary artery layers of OCT imaging obtained from a series of KD patients. Our approach is focused on developing a robust Random Forest classifier built on the idea of randomly selecting a subset of features at each node and based on second- and higher-order statistical texture analysis which estimates the gray-level spatial distribution of images by specifying the local features of each pixel and extracting the statistics from their distribution. The average classification accuracy for intima and media are 76.36% and 73.72% respectively. Random forest classifier with texture analysis promises for classification of coronary artery tissue.

  15. Pulp tissue from primary teeth: new source of stem cells

    Directory of Open Access Journals (Sweden)

    Paloma Dias Telles

    2011-06-01

    Full Text Available SHED (stem cells from human exfoliated deciduous teeth represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin.

  16. Kimura's disease: A case presentation of postauricular swelling ...

    African Journals Online (AJOL)

    Kimura's disease: A case presentation of postauricular swelling. A Rajesh, T Prasanth, V.C. Naga Sirisha, M.D.S. Azmi. Abstract. Kimura's disease (KD) is a rare chronic inflammatory disease of subcutaneous tissues and occurs predominantly in head and neck region. It is seen primarily in young Asian males. Typical clinical ...

  17. Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic

    Energy Technology Data Exchange (ETDEWEB)

    Ghanaati, Shahram; Barbeck, Mike; Kirkpatrick, C James [REPAIR-Lab, Institute of Pathology, Johannes Gutenberg University, Mainz (Germany); Schlee, Markus [Bayreuther Strasse 39, D-91301, Forchheim (Germany); Webber, Matthew J [Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208 (United States); Willershausen, Ines [Institute for Dental Material Sciences and Technology, University Medical Center of the Johannes Gutenberg University, Mainz (Germany); Balic, Ela; Goerlach, Christoph [Geistlich Pharma AG, Wolhusen (Switzerland); Stupp, Samuel I [Department of Materials Science and Engineering, Chemistry, and Medicine, Northwestern University, Evanston, IL 60208 (United States); Sader, Robert A, E-mail: ghanaati@uni-mainz.de [Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt Am Main (Germany)

    2011-02-15

    This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

  18. Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic

    International Nuclear Information System (INIS)

    Ghanaati, Shahram; Barbeck, Mike; Kirkpatrick, C James; Schlee, Markus; Webber, Matthew J; Willershausen, Ines; Balic, Ela; Goerlach, Christoph; Stupp, Samuel I; Sader, Robert A

    2011-01-01

    This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

  19. Wilson's disease: cranial MRI observations and clinical correlation

    International Nuclear Information System (INIS)

    Sinha, S.; Taly, A.B.; Prashanth, L.K.; Venugopal, K.S.; Arunodaya, G.R.; Swamy, H.S.; Ravishankar, S.; Vasudev, M.K.

    2006-01-01

    Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD. MRI evaluation was carried out in 100 patients (57 males, 43 females; mean age 19.3±8.9 years) using standard protocols. All but 18 patients were on de-coppering agents. Their history, clinical manifestations and scores for severity of disease were noted. The mean duration of illness and treatment were 8.3±10.8 years and 7.5±7.1 years respectively. MRI of the brain was abnormal in all the 93 symptomatic patients. The most conspicuous observations were atrophy of the cerebrum (70%), brainstem (66%) and cerebellum (52%). Signal abnormalities were also noted: putamen (72%), caudate (61%), thalami (58%), midbrain (49%), pons (20%), cerebral white matter (25%), cortex (9%), medulla (12%) and cerebellum (10%). The characteristic T2-W globus pallidal hypointensity (34%), ''Face of giant panda'' sign (12%), T1-W striatal hyperintensity (6%), central pontine myelinosis (7%), and bright claustral sign (4%) were also detected. MRI changes correlated with disease severity scores (P<0.001) but did not correlate with the duration of illness. MRI changes were universal but diverse and involved almost all the structures of the brain in symptomatic patients. A fair correlation between MRI observations and various clinical features provides an explanation for the protean manifestations of the disease. (orig.)

  20. MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

    Science.gov (United States)

    Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

    2015-04-01

    Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

  1. Molecular analysis of infectious bursal disease virus from bursal tissues collected on FTA filter paper.

    Science.gov (United States)

    Moscoso, Hugo; Alvarado, Ivan; Hofacre, Charles L

    2006-09-01

    We investigated the feasibility of using FTA filter cards for the storage of bursas of Fabricius containing infectious bursal disease virus (IBDV) and for IBDV detection by reverse transcriptase (RT)-polymerase chain reaction (PCR), and characterization by restriction fragment length polymorphism (RFLP) or nucleotide sequencing. The FTA card is a cotton-based cellulose membrane containing lyophilized chemicals that lyses many types of bacteria and viruses. IBDV was inactivated upon contact with the FTA as shown by the inability of the virus to be propagated in embryonating chicken eggs. Viral RNA in minced bursas or stamped bursas could be amplified by RT-PCR (VP2 gene fragment, 248 base pairs) after storage on FTA for at least 15 days at room temperature or 8 mo at -20 C. Analytical sensitivity of the test was between 0.5-5 ng of RNA template or 5 x 10(1) mean tissue culture infective dose (TCID50)/FTA spot. Detection rate of IBDV in domestic clinical samples collected on FTA or collected by the non-FTA standard procedure was 36.7% and 41.7%, respectively, which represents 88% agreement. Detection of IBDV from FTA cards inoculated with bursal tissues in the laboratory or in the field was 36.7% and 37.1%, respectively. Detection of IBDV from FTA samples when the cards were inoculated with bursal tissues and sent through customs into the United States was 32.9%. Analysis of the amplified products showed that molecular characterization of IBDV by RFLP or nucleotide sequencing is feasible in bursas stored on FTA at 25 C for 1-3 mo or at -20 C for at least 8 mo. The use of FTA for the collection of bursal tissues and simultaneous inactivation of IBDV allows the movement of specimens within the United States and also from outside the United States in compliance with federal regulations and in a manner adequate for molecular characterization.

  2. From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

    Science.gov (United States)

    Borovjagin, Anton V.; Ogle, Brenda; Berry, Joel; Zhang, Jianyi

    2016-01-01

    Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional two-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and pre-clinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents. PMID:28057791

  3. Use of intrinsic fluorescent signals for characterizing tissue metabolic states in health and disease

    Science.gov (United States)

    Chance, Britton

    1996-04-01

    The large content of mitochondria in metabolizing cells, coupled with intrinsic NADH and flavoprotein signals makes these signals ideal for characterizing tissue metabolic states in health and disease. The first few millimeters of tissue are reached by the fluorescence excitation in the exposed surfaces of the cervix, bladder, rectum and esophagus, etc. Thus, extensive use has been made of fluorescent signals by a large number of investigators for tumor diagnosis from an empirical standpoint where the fluorescent signals are generally diminished in precancerous and cancerous tissue. This article reviews the biochemical basis for the fluorescent signals and points to a 'gold standard' for fluorescent signal examination involving freeze trapping and low temperature two- or three-dimensional high resolution fluorescence spectroscopy.

  4. The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

    2018-01-09

    Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

  5. Comparing Clinical Profiles in Alzheimer's Disease and Parkinson's Disease Dementia

    Directory of Open Access Journals (Sweden)

    Martin R. Farlow

    2013-09-01

    Full Text Available Background: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD and Parkinson's disease dementia (PDD may improve the interpretation of drug effects and the design of future studies. Methods: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD. Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog, Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL scale, 10-item Neuropsychiatric Inventory (NPI-10 and the ADCS-Clinical Global Impression of Change (CGIC was compared [standardized difference (Cohen's d, similar if Results: Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47 and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58 were higher in AD; PDD patients were more impaired in the language (0.23 and praxis (0.34 domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14 and improvement on the NPI-10 (0.11 compared with patients with PDD. Conclusion: Differing patterns of impairment occur in AD and PDD.

  6. Comparing clinical profiles in Alzheimer's disease and Parkinson's disease dementia.

    Science.gov (United States)

    Farlow, Martin R; Schmitt, Frederick; Aarsland, Dag; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

    2013-01-01

    Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies. This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1]. Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47) and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58) were higher in AD; PDD patients were more impaired in the language (0.23) and praxis (0.34) domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14) and improvement on the NPI-10 (0.11) compared with patients with PDD. Differing patterns of impairment occur in AD and PDD.

  7. Expression of the stem cell factor in fibroblasts, endothelial cells, and macrophages in periapical tissues in human chronic periapical diseases.

    Science.gov (United States)

    Shen, S Q; Wang, R; Huang, S G

    2017-03-08

    Stem cell factor (SCF), an important stem cell cytokine, has multiple functions. Fibroblasts (FBs), mature mast cells, endothelial cells (ECs), and eosinophil granulocytes can produce SCF in the inflammatory process. Therefore, we aimed to observe SCF expression in FBs, ECs, and macrophages (MPs) in periapical tissues in human chronic periapical disease and investigate the effects of cells expressing SCF in pathogenesis of the disease. Healthy (N = 20), periapical cyst (N = 15), and periapical granuloma (N = 15) tissues were fixed in 10% formalin for 48 h, embedded in paraffin, and stained with hematoxylin and eosin to observe histological changes. SCF expression was observed in FBs, ECs, and MPs in periapical tissues by double immunofluorescence. CD334, CD31, and CD14 are specific markers of FBs, ECs, and MPs, respectively. Results showed that densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs were significantly increased in periapical tissue groups (P periapical tissue groups (P > 0.05). CD14-SCF double-positive MP density was considerably higher in periapical granulomas than in cysts (P periapical tissues, suggesting that the cells might be related to occurrence, development, and pathogenesis of chronic periapical disease.

  8. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

    2009-01-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  9. Clinical application of SPECT and PET in cerebrovascular disease

    International Nuclear Information System (INIS)

    Ra, Young Shin

    2003-01-01

    Single photon emission computed tomography(SPECT) and positron emission tomography(PET) are modern imaging techniques that allow for both qualitative are quantitative assessment of hemodynamic changes in cerebrovascular diseases. SPECT has been becoming an indispensable method to investigate regional cerebral blood flow because equipment and isotope are easily available in most general hospitals. Acetazolamide stress SPECT has also been proved to be useful to evaluate the cerebrovascular reserve of occlusive cerebrovascular diseases and to select surgical candidate. PET has gained wide spread clinical use in the evaluation of the hemodynamic and metabolic consequences of extracranial or intracranial arterial obstructive disease despite its complexity and limited availability. PET has been established as an invaluable tool in the pathophysilogy investigation of acute ischemic stroke. The potentials, limitations, and clinical applications of SPECT and PET in various cerebrovascular diseases will be discussed in this article with reviews of literatures

  10. Clinical application of SPECT and PET in cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Ra, Young Shin [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2003-02-01

    Single photon emission computed tomography(SPECT) and positron emission tomography(PET) are modern imaging techniques that allow for both qualitative are quantitative assessment of hemodynamic changes in cerebrovascular diseases. SPECT has been becoming an indispensable method to investigate regional cerebral blood flow because equipment and isotope are easily available in most general hospitals. Acetazolamide stress SPECT has also been proved to be useful to evaluate the cerebrovascular reserve of occlusive cerebrovascular diseases and to select surgical candidate. PET has gained wide spread clinical use in the evaluation of the hemodynamic and metabolic consequences of extracranial or intracranial arterial obstructive disease despite its complexity and limited availability. PET has been established as an invaluable tool in the pathophysilogy investigation of acute ischemic stroke. The potentials, limitations, and clinical applications of SPECT and PET in various cerebrovascular diseases will be discussed in this article with reviews of literatures.

  11. Rhinovirus/enterovirus RNA in tonsillar tissue of children with tonsillar disease.

    Science.gov (United States)

    Suvilehto, Jari; Roivainen, Merja; Seppänen, Mikko; Meri, Seppo; Hovi, Tapani; Carpén, Olli; Pitkäranta, Anne

    2006-03-01

    Human rhinoviruses (HRVs) together with the closely related human enteroviruses (HEVs) cause most of the acute respiratory illnesses throughout the year. HRVs have been detected in most parts of the respiratory tract but not in pharyngeal tonsils. We aimed to find out whether HRVs were detectable in tonsillar tissue and if their presence correlated to the tonsillar disease. Thirty-three tonsillar samples collected in February-March 2003 from children with no acute respiratory symptoms were studied with HRV in situ hybridization (HRV-ISH). Ten tonsillar samples were further examined in a separate laboratory by two different reverse transcription polymerase chain reaction (RT-PCR) methods designed for detection of HRV/HEV RNA. Twenty of the 33 samples (62%) were positive by HRV-ISH. Five positive and five negative HRV-ISH samples were investigated by two different PCR methods. HRV/HEV RNA was detected in 9 of the 10 specimens by a hanging drop-nested PCR. One HRV-ISH negative sample was positive by a conventional non-nested PCR. One of the samples studied by all three methods, from a patient with recurrent tonsillitis, had no detectable HRV/HEV RNA. Positive result in HRV-ISH did not correlate significantly with underlying tonsillar disease, history of respiratory infections or bronchial asthma. Altogether HRV/HEV RNA was detected in 75% of the tonsils with no correlation to patients' operation indication or history of respiratory diseases. In February-March, HRV/HEV RNA was frequently found in tonsillar tissue in children irrespective of the tonsillar pathology. Whether detection of the RNA is a marker of chronic infection or is merely remnant of past infection is not known.

  12. The Affordability of Providing Sexually Transmitted Disease Services at a Safety-net Clinic.

    Science.gov (United States)

    Dean, Lorraine T; Montgomery, Madeline C; Raifman, Julia; Nunn, Amy; Bertrand, Thomas; Almonte, Alexi; Chan, Philip A

    2018-04-01

    Sexually transmitted diseases continue to increase in the U.S. There is a growing need for financially viable models to ensure the longevity of safety-net sexually transmitted disease clinics, which provide testing and treatment to high-risk populations. This micro-costing analysis estimated the number of visits required to balance cost and revenue of a sexually transmitted disease clinic in a Medicaid expansion state. In 2017, actual and projected cost and revenues were estimated from the Rhode Island sexually transmitted disease clinic in 2015. Projected revenues for a hypothetical clinic offering a standard set of sexually transmitted disease services were based on Medicaid; private ("commercial") insurance; and institutional ("list price") reimbursement rates. The number of visits needed to cover clinic costs at each rate was assessed. Total operating cost for 2,153 clinic visits was estimated at $255,769, or $119 per visit. Laboratory testing and salaries each accounted for 44% of operating costs, medications for treatment 7%, supplies 5%, and 28% of visits used insurance. For a standard clinic offering a basic set of sexually transmitted disease services to break even, a projected 73% of visits need to be covered at the Medicaid rate, 38% at private rate, or 11% at institutional rate. Sexually transmitted disease clinics may be financially viable when a majority of visits are billed at a Medicaid rate; however, mixed private/public models may be needed if not all visits are billed. In this manner, sexually transmitted disease clinics can be solvent even if not all visits are billed to insurance, thus ensuring access to uninsured or underinsured patients. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Illumina MiSeq 16S amplicon sequence analysis of bovine respiratory disease associated bacteria in lung and mediastinal lymph node tissue.

    Science.gov (United States)

    Johnston, Dayle; Earley, Bernadette; Cormican, Paul; Murray, Gerard; Kenny, David Anthony; Waters, Sinead Mary; McGee, Mark; Kelly, Alan Kieran; McCabe, Matthew Sean

    2017-05-02

    Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract. The objective of this study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung and lymph node tissue samples harvested from fatal BRD cases and clinically healthy animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue samples were collected from calves diagnosed as BRD cases by veterinary laboratory pathologists and from clinically healthy calves. NGS 16S amplicon libraries, targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology (QIIME) was used to determine operational taxonomic units (OTUs) which corresponded to the 16S rRNA gene sequences. Leptotrichiaceae, Mycoplasma, Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae, Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative abundances in post-mortem lung samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances in post-mortem lymph node samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Two Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-enriched shotgun sequences

  14. Soft Tissue Sarcoma

    Science.gov (United States)

    ... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

  15. The detection, diagnosis, therapy, and pre-clinical biology of breast cancer

    International Nuclear Information System (INIS)

    1978-01-01

    The Cancergram covers clinical aspects of cancers of the mammary glands, the fat pads and the supporting tissues. Abstracts included concern certain specific types of neoplasms which occur in the breast, and in ancillary tissues related to the breast (axillary lymph nodes, etc.). Also included are selected studies on receptors and the physiological aspects of lactation, pregnancy, and ontogeny related to cancer of the breast. The topic includes clinically relevant aspects of the prevention, detection, diagnosis, evaluation, and therapy of breast cancer. With certain exceptions, pre-clinical studies of tissue culture systems or animal model studies which are not directly related to primary human disease are excluded

  16. Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease.

    Directory of Open Access Journals (Sweden)

    Ying Sun

    Full Text Available Gaucher disease results from GBA1 mutations that lead to defective acid β-glucosidase (GCase mediated cleavage of glucosylceramide (GC and glucosylsphingosine as well as heterogeneous manifestations in the viscera and CNS. The mutation, tissue, and age-dependent accumulations of different GC species were characterized in mice with Gba1 missense mutations alone or in combination with isolated saposin C deficiency (C*. Gba1 heteroallelism for D409V and null alleles (9V/null led to GC excesses primarily in the visceral tissues with preferential accumulations of lung GC24∶0, but not in liver, spleen, or brain. Age-dependent increases of different GC species were observed. The combined saposin C deficiency (C* with V394L homozygosity (4L;C* showed major GC18:0 degradation defects in the brain, whereas the analogous mice with D409H homozygosity and C* (9H;C* led to all GC species accumulating in visceral tissues. Glucosylsphingosine was poorly degraded in brain by V394L and D409H GCases and in visceral tissues by D409V GCase. The neonatal lethal N370S/N370S genotype had insignificant substrate accumulations in any tissue. These results demonstrate age, organ, and mutation-specific quantitative differences in GC species and glucosylsphingosine accumulations that can have influence in the tissue/regional expression of Gaucher disease phenotypes.

  17. Adiponectin and Its Receptors Are Differentially Expressed in Human Tissues and Cell Lines of Distinct Origin

    Directory of Open Access Journals (Sweden)

    Simon Jasinski-Bergner

    2017-12-01

    Full Text Available Background: Adiponectin is secreted by adipose tissue and exerts high abundance and an anti-inflammatory potential. However, only little information exists about the expression profiles of adiponectin and its recently identified receptor CDH13 in non-tumorous human tissues and their association to clinical parameters. Methods: The expression levels of adiponectin and CDH13 were analyzed in heart, liver, kidney, spleen, skin, blood vessels, peripheral nerve and bone marrow of 21 human body donors, in 12 human cell lines, and in purified immune effector cell populations of healthy blood donors by immunohistochemistry, Western-blot, and semi-quantitative PCR. The obtained results were then correlated to clinical parameters, including age, sex and known diseases like cardiovascular and renal diseases. Results: Adiponectin expression in renal corpuscles was significantly higher in humans with known renal diseases. A coordinated expression of adiponectin and CDH13 was observed in the myocard. High levels of adiponectin could be detected in the bone marrow, in certain lymphoid tumor cell lines and in purified immune effector cell populations of healthy donors, in particular in cytotoxic T cells. Conclusion: For the first time, the expression profiles of adiponectin and CDH13 are analyzed in many human tissues in correlation to each other and to clinical parameters.

  18. [Tissue repositories for research at Sheba Medical Center(SMC].

    Science.gov (United States)

    Cohen, Yehudit; Barshack, Iris; Onn, Amir

    2013-06-01

    Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular

  19. Bioprinting towards Physiologically Relevant Tissue Models for Pharmaceutics.

    Science.gov (United States)

    Peng, Weijie; Unutmaz, Derya; Ozbolat, Ibrahim T

    2016-09-01

    Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Clinical-histopathological correlation in a case of Coats' disease

    Directory of Open Access Journals (Sweden)

    Zajdenweber Moyses E

    2006-08-01

    Full Text Available Abstract Background Coats' disease is a non-hereditary ocular disease, with no systemic manifestation, first described by Coats in 1908. It occurs more commonly in children and has a clear male predominance. Most patients present clinically with unilateral decreased vision, strabismus or leukocoria. The most important differential diagnosis is unilateral retinoblastoma, which occurs in the same age group and has some overlapping clinical manifestations. Case presentation A 4 year-old girl presented with a blind and painful right eye. Ocular examination revealed neovascular glaucoma, cataract and posterior synechiae. Although viewing of the fundus was impossible, computed tomography disclosed total exsudative retinal detachment in the affected eye. The eye was enucleated and subsequent histopathological evaluation confirmed the diagnosis of Coats' disease. Conclusion General pathologists usually do not have the opportunity to receive and study specimens from patients with Coats' disease. Coats' disease is one of the most important differential diagnoses of retinoblastoma. Therefore, It is crucial for the pathologist to be familiar with the histopathological features of the former, and distinguish it from the latter.

  1. [Clinical and morphological variants of diverticular disease in colon].

    Science.gov (United States)

    Levchenko, S V; Lazebnik, L B; Potapova, V B; Rogozina, V A

    2013-01-01

    Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

  2. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  3. Genetics of liver disease: From pathophysiology to clinical practice.

    Science.gov (United States)

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Pilonidal sinus disease - Etiological factors, pathogenesis and clinical features

    Directory of Open Access Journals (Sweden)

    Kazim Duman

    2016-12-01

    Full Text Available and lsquo;Pilonidal sinus' disease, which is most commonly seen in reproductive populations, such as young adults - mostly in males who are in their twenties - is actually a controversial disease in that there is no consensus on its many facets. It is sometimes seen as an infected abscess draining from an opening or a lesion extending to the perineum. It may also present as a draining fistula opening to skin. In terms of etiological factors, various theories (main theories being congenital and acquired have been established since it was first described, no universal understanding achieved. A long and significant post-operative care period with different lengths of recovery depending on the type of operation are quite prevalent with regards to recurrence and complication status. In order to prevent recurrence and improve the quality of life, etiological and predisposing factors as well as clinical features of sacrococcygeal pilonidal disease should be well known, a detailed differential diagnosis should be made, and a suitable and timely intervention should be performed. It was aimed here to explain the etiological factors, pathogenesis and clinical features of the disease that may present with various clinical symptoms. [Arch Clin Exp Surg 2016; 5(4.000: 228-232

  5. Automated interpretable computational biology in the clinic: a framework to predict disease severity and stratify patients from clinical data

    Directory of Open Access Journals (Sweden)

    Soumya Banerjee

    2017-10-01

    Full Text Available We outline an automated computational and machine learning framework that predicts disease severity and stratifies patients. We apply our framework to available clinical data. Our algorithm automatically generates insights and predicts disease severity with minimal operator intervention. The computational framework presented here can be used to stratify patients, predict disease severity and propose novel biomarkers for disease. Insights from machine learning algorithms coupled with clinical data may help guide therapy, personalize treatment and help clinicians understand the change in disease over time. Computational techniques like these can be used in translational medicine in close collaboration with clinicians and healthcare providers. Our models are also interpretable, allowing clinicians with minimal machine learning experience to engage in model building. This work is a step towards automated machine learning in the clinic.

  6. Clinical presentation of late haemorrhagic disease of newborn

    International Nuclear Information System (INIS)

    Majeed, R.; Memon, Y.; Majeed, F.

    2008-01-01

    To observe the clinical presentation of late haemorrhagic disease of the newborn (LHDNB), and clinical improvement after the administration of vitamin K/sub 1/. This is a prospective descriptive study. All the children older than seven days who presented with bleeding were admitted in pediatrics ward of Isra University Hyderabad from April 2006 to April 2007 were included. Data collection was done by means of detailed proforma. Analysis was done on SPSS version 11. Thirty five cases were included. Commonest site of bleeding was subcutaneous followed by oral and injection site. Mean age of late haemorrhagic disease of newborn was 109 days and minimum age of presentation was 28 days. Common clinical presentations were irritability, convulsions, poor reflexes and poor feeding. Mostly recovery was within 24 hours after vit K. Late HDN results in severe hemorrhage especially hemorrhage in the central nervous system. Administration of Vitamin K (1mg, 1M) at birth can present these severe complications. (author)

  7. Clinical heterogeneity in newly diagnosed Parkinson's disease

    NARCIS (Netherlands)

    Post, Bart; Speelman, Johannes D.; de Haan, Rob J.

    2008-01-01

    OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy. METHODS: We conducted a k-means cluster analysis in a prospective

  8. Periodontal status affects C-reactive protein and lipids in patients with stable heart disease from a tertiary care cardiovascular clinic.

    Science.gov (United States)

    Flores, Manuela F; Montenegro, Marlon M; Furtado, Mariana V; Polanczyk, Carisi A; Rösing, Cassiano K; Haas, Alex N

    2014-04-01

    There are scarce data on the impact of the periodontal condition in the control of biomarkers in patients with cardiovascular disease (CVD). The aim of this study is to assess whether periodontal inflammation and tissue breakdown are associated with C-reactive protein (CRP) and lipids in patients with stable heart disease. This cross-sectional study included 93 patients with stable coronary artery disease (57 males; mean age: 63.5 ± 9.8 years) who were in outpatient care for at least 6 months. After applying a structured questionnaire, periodontal examinations were performed by two calibrated periodontists in six sites per tooth at all teeth. Blood samples were collected from patients on the day of periodontal examination to determine levels of CRP, lipids, and glycated hemoglobin. Multiple linear regression models were fitted to evaluate the association among different periodontal and blood parameters controlling for sex, body mass index, glycated hemoglobin, use of oral hypoglycemic drugs, and smoking. Overall, the sample presented high levels of periodontal inflammation and tissue breakdown. Unadjusted mean concentrations of triglycerides (TGs), very-low-density lipoprotein cholesterol, and glucose were significantly higher in individuals with severe periodontitis. When multiple linear regression models were applied, number of teeth with clinical attachment loss ≥6 mm and presence of severe periodontitis were significantly associated with higher CRP concentrations. Bleeding on probing was significantly associated with TGs, total cholesterol, and non-high-density lipoprotein cholesterol. In this sample of patients with stable CVD, current periodontal inflammation and tissue breakdown are associated with cardiovascular inflammatory markers, such as CRP and lipid profile.

  9. Biobanking of fresh frozen tissue from clinical surgical specimens: transport logistics, sample selection, and histologic characterization.

    Science.gov (United States)

    Botling, Johan; Micke, Patrick

    2011-01-01

    Access to high-quality fresh frozen tissue is critical for translational cancer research and molecular -diagnostics. Here we describe a workflow for the collection of frozen solid tissue samples derived from fresh human patient specimens after surgery. The routines have been in operation at Uppsala University Hospital since 2001. We have integrated cryosection and histopathologic examination of each biobank sample into the biobank manual. In this way, even small, macroscopically ill-defined lesions can be -procured without a diagnostic hazard due to the removal of uncharacterized tissue from a clinical -specimen. Also, knowledge of the histomorphology of the frozen tissue sample - tumor cell content, stromal components, and presence of necrosis - is pivotal before entering a biobank case into costly molecular profiling studies.

  10. Idiopathic Canalicular Inflammatory Disease: New Disease Description of Clinical Patterns, Investigations, Management, and Outcomes.

    Science.gov (United States)

    Ali, Mohammad Javed

    2018-01-25

    The objective of this perspective is to present a separate disease description of "idiopathic canalicular inflammatory disease" and outline the diagnostic criteria and early experiences with its investigations and management. Retrospective case series of 44 canaliculi of 22 eyes of 11 patients presenting at a tertiary care Dacryology service over a period of 2 years with typical clinical patterns of inflammatory canaliculitis and its outcomes were studied. All the patients underwent microbiological work-up with culture and sensitivity, dacryoendoscopy imaging, serial Fourier domain ocular coherence tomography, and collagen vascular profiles. Stages in the evolution of the disease were studied. All patients were treated initially with topical steroids followed by punctal dilatation and placement of mini-monoka stents. Five patients in addition had a small biopsy from the inflamed portion of the vertical canaliculus. Stents were extubated at 6 weeks. Forty-four canaliculi were diagnosed to have idiopathic canalicular inflammatory disease during the study period. There was a female preponderance (81.8%, 9/11) and the mean age at presentation was 57 years. All patients presented with unilateral epiphora without any discharge, pain, or swelling. Collagen vascular profiles and screening for autoimmune diseases were negative. Clinical picture ranged from stages 1 to 5, consisting of edema, progressive centripetal vascularization, pouting of vascularized mucosa, membrane formation, and progressive scarring. The presentation begins in 1 eye and usually involves the other eye at a mean of 6 months. Ocular coherence tomography and dacryoendoscopy were of adjunctive value in the diagnosis. Histopathological examination was suggestive of a chronic inflammation. All patients had relentless progression to end-stage disease, although delayed significantly by steroids and monoka intubation. Idiopathic canalicular inflammatory disease has a distinct and typical clinical behavior and

  11. Update on the clinical management of Wilson's disease

    Directory of Open Access Journals (Sweden)

    Hedera P

    2017-01-01

    Full Text Available Peter Hedera Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Wilson’s disease (WD, albeit relatively rare, is an important genetic metabolic disease because of highly effective therapies that can be lifesaving. It is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Neurologic, psychiatric and hepatologic problems in WD are very nonspecific, and we discuss the most common clinical phenotypes. The diagnosis remains laboratory based, and here we review the most important challenges and pitfalls in laboratory evaluation of WD, including the emerging role of genetic testing in WD diagnosis. WD is a monogenic disorder but has very high allelic heterogeneity with >500 disease-causing mutations identified, and new insights into phenotype–genotype correlations are also reviewed. The gold standard of therapy is chelation of excessive copper, but many unmet needs exist because of possible clinical deterioration in treated patients and potential adverse effects associated with currently available chelating medications. We also review the most promising novel therapeutic approaches, including chelators targeting specific cell types, cell transplantation and gene therapy. Keywords: Wilson’s disease, copper, ATP7B, chelation, gene therapy

  12. The Infectious Diseases Society of America emerging infections network: bridging the gap between clinical infectious diseases and public health.

    Science.gov (United States)

    Pillai, Satish K; Beekmann, Susan E; Santibanez, Scott; Polgreen, Philip M

    2014-04-01

    In 1995, the Centers for Disease Control and Prevention granted a Cooperative Agreement Program award to the Infectious Diseases Society of America to develop a provider-based emerging infections sentinel network, the Emerging Infections Network (EIN). Over the past 17 years, the EIN has evolved into a flexible, nationwide network with membership representing a broad cross-section of infectious disease physicians. The EIN has an active electronic mail conference (listserv) that facilitates communication among infectious disease providers and the public health community, and also sends members periodic queries (short surveys on infectious disease topics) that have addressed numerous topics relevant to both clinical infectious diseases and public health practice. The article reviews how the various functions of EIN contribute to clinical care and public health, identifies opportunities to further link clinical medicine and public health, and describes future directions for the EIN.

  13. Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji.

    Science.gov (United States)

    Engelman, Daniel; Mataika, Reapi L; Ah Kee, Maureen; Donath, Susan; Parks, Tom; Colquhoun, Samantha M; Carapetis, Jonathan R; Kado, Joseph H; Steer, Andrew C

    2017-08-01

    Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (pFiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... and organs in tissue-engineering protocols. However, several challenges confront the use of these cells in the clinic, ranging from biological challenges (e.g., how to isolate a homogenous populations of the cells with specific criteria from the bone marrow and how to expand them ex vivo without affecting...

  15. Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine.

    Science.gov (United States)

    Elloumi-Hannachi, I; Yamato, M; Okano, T

    2010-01-01

    Cell sheet technology (CST) is based on the use of thermoresponsive polymers, poly(N-isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in such a way as to make its typical thickness <100 nm. In this review, we first focus on how the methods of PIPAAm-grafted surface preparations and functionalization are important to be able to harvest a functional cell sheet, to be further transplanted. Then, we present aspects of tissue mimics and three-dimensional reconstruction of a tissue in vitro. Finally, we give an overview of clinical applications and clinically relevant animal experimentations of the technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal ulcerations and type 1 diabetes.

  16. Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

    Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

  17. MINIMALLY INVASIVE SINGLE FLAP APPROACH WITH CONNECTIVE TISSUE WALL FOR PERIODONTAL REGENERATION

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2017-09-01

    Full Text Available INTRODUCTION: The destructive periodontal diseases are among the most prevalent in the human population. In some cases, bony defects are formed during the disease progression, thus sustaining deep periodontal pockets. The reconstruction of these defects is usually done with the classical techniques of bone substitutes placement and guided tissue regeneration. The clinical and histological data from the recent years, however, demonstrate the relatively low regenerative potential of these techniques. The contemporary approaches for periodontal regeneration rely on minimally invasive surgical protocols, aimed at complete tissue preservation in order to achieve and maintain primary closure and at stimulating the natural regenerative potential of the periodontal tissues. AIM: This presentation demonstrates the application of a new, minimally invasive, single flap surgical technique for periodontal regeneration in a clinical case with periodontitis and a residual deep intrabony defect. MATERIALS AND METHODS: A 37 years old patient presented with chronic generalised periodontitis. The initial therapy led to good control of the periodontal infection with a single residual deep periodontal pocket medially at 11 due to a deep intrabony defect. A single flap approach with an enamel matrix derivate application and a connective tissue wall technique were performed. The proper primary closure was obtained. RESULT: One month after surgery an initial mineralisation process in the defect was detected. At the third month, a complete clinical healing was observed. The radiographic control showed finished bone mineralisation and periodontal space recreation. CONCLUSION: In the limitation of the presented case, the minimally invasive surgical approach led to complete clinical healing and new bone formation, which could be proof for periodontal regeneration.

  18. [Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

    Science.gov (United States)

    Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

    2013-10-01

    A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  19. Rethinking dry eye disease: a perspective on clinical implications.

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    Bron, Anthony J; Tomlinson, Alan; Foulks, Gary N; Pepose, Jay S; Baudouin, Christophe; Geerling, Gerd; Nichols, Kelly K; Lemp, Michael A

    2014-04-01

    Publication of the DEWS report in 2007 established the state of the science of dry eye disease (DED). Since that time, new evidence suggests that a rethinking of traditional concepts of dry eye disease is in order. Specifically, new evidence on the epidemiology of the disease, as well as strategies for diagnosis, have changed the understanding of DED, which is a heterogeneous disease associated with considerable variability in presentation. These advances, along with implications for clinical care, are summarized herein. The most widely used signs of DED are poorly correlated with each other and with symptoms. While symptoms are thought to be characteristic of DED, recent studies have shown that less than 60% of subjects with other objective evidence of DED are symptomatic. Thus the use of symptoms alone in diagnosis will likely result in missing a significant percentage of DED patients, particularly with early/mild disease. This could have considerable impact in patients undergoing cataract or refractive surgery as patients with DED have less than optimal visual results. The most widely used objective signs for diagnosing DED all show greater variability between eyes and in the same eye over time compared with normal subjects. This variability is thought to be a manifestation of tear film instability which results in rapid breakup of the tearfilm between blinks and is an identifier of patients with DED. This feature emphasizes the bilateral nature of the disease in most subjects not suffering from unilateral lid or other unilateral destabilizing surface disorders. Instability of the composition of the tears also occurs in dry eye disease and shows the same variance between eyes. Finally, elevated tear osmolarity has been reported to be a global marker (present in both subtypes of the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically, osmolarity has been shown to be the best single metric for diagnosis of DED and is directly related to

  20. Design and Evaluation of a Bacterial Clinical Infectious Diseases Ontology

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    Gordon, Claire L.; Pouch, Stephanie; Cowell, Lindsay G.; Boland, Mary Regina; Platt, Heather L.; Goldfain, Albert; Weng, Chunhua

    2013-01-01

    With antimicrobial resistance increasing worldwide, there is a great need to use automated antimicrobial decision support systems (ADSSs) to lower antimicrobial resistance rates by promoting appropriate antimicrobial use. However, they are infrequently used mostly because of their poor interoperability with different health information technologies. Ontologies can augment portable ADSSs by providing an explicit knowledge representation for biomedical entities and their relationships, helping to standardize and integrate heterogeneous data resources. We developed a bacterial clinical infectious diseases ontology (BCIDO) using Protégé-OWL. BCIDO defines a controlled terminology for clinical infectious diseases along with domain knowledge commonly used in hospital settings for clinical infectious disease treatment decision-making. BCIDO has 599 classes and 2355 object properties. Terms were imported from or mapped to Systematized Nomenclature of Medicine, Unified Medical Language System, RxNorm and National Center for Bitechnology Information Organismal Classification where possible. Domain expert evaluation using the “laddering” technique, ontology visualization, and clinical notes and scenarios, confirmed the correctness and potential usefulness of BCIDO. PMID:24551353