Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

Directory of Open Access Journals (Sweden)

O.V. Gudym

2017-08-01

Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

[Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].

Science.gov (United States)

Baccaro, Fernando; Moldes, Sofía; Novelli Poisson, Paola; Arduin, Julieta; Valerga, Mario

2012-01-01

Syphilis remains a common disease throughout the world, being neurosyphilis a relatively common manifestation. A case of a 34 years old male with HIV and neurosyphilis is presented, characterized by a clinical course evidenced by progressive palsy of cranial nerves. This case is unusual and a rare presentation of progressive cranial involvement with swallowing deficit, have found no similar data in the literature.

An Unusual Case of Rapidly Progressive Hyperbilirubinemia

Directory of Open Access Journals (Sweden)

Kimberly M. Thornton

2013-01-01

Full Text Available We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient’s diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period.

Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report

Directory of Open Access Journals (Sweden)

Lekwuwa Godwin

2010-12-01

Full Text Available Abstract Introduction We describe a case of rapidly progressive and severely debilitating polyneuropathy in a patient with confirmed hypovitaminosis B1, consistent with dry beriberi. Crucially, this is a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Case presentation A 49-year-old Caucasian British man presented with progressive weakness of both lower limbs of approximately seven months' duration. He noted difficulty climbing stairs. He also complained of lethargy, and loss of muscle bulk, including his thighs. He had a history of type 2 diabetes mellitus and admitted prior alcohol abuse but denied excessive alcohol intake in the five years prior to presentation. Initial clinical and neurophysiological examinations were consistent with a mild peripheral neuropathy and probable proximal myopathy. However, over the subsequent four months he evolved a marked tetraparesis, with profound sensory disturbance of all limbs. Repeat neurophysiology revealed a widespread polyneuropathy with extensive acute and sub-acute denervation changes in all four limbs, and reduced or absent sensory nerve action potentials. Hypovitaminosis B1 was confirmed (45 nmol/L, reference range 66-200 nmol/L. His rapid clinical deterioration was in keeping with dry beriberi. He was treated with thiamine. Subsequent follow-up revealed slow but significant improvement, such that by 15-16 months from the initial onset of symptoms, and approximately six months after the onset of his marked tetraparesis, he was able to stand independently and was gradually gaining confidence in walking pending a period of in-patient neurorehabilitation. Conclusion A potentially wide differential diagnosis exists for this type of presentation. Confirming hypovitaminosis B1 by requesting the assay prior to vitamin replacement ensures accurate diagnosis and

Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

Science.gov (United States)

Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

2015-01-01

The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

ANCA-GBM dot-blot : Evaluation of an assay in the differential diagnosis of patients presenting with rapidly progressive glomerulonephritis

NARCIS (Netherlands)

Rutgers, Abraham; Damoiseaux, Jan; Roozendaal, Caroline; Limburg, Pieter C; Stegeman, Coen A; Tervaert, Jan Willem Cohen

Rapidly progressive glomerulonephritis (RPGN) is characterized by rapid and progressive loss of renal function and the presence of crescentic glomerulonephritis (CGN). Early diagnosis and appropriate treatment is mandatory to prevent death and/or renal failure. We have evaluated an ANCA-GBM dot-blot

[Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in children].

Science.gov (United States)

Jellouli, Manel; Maghraoui, Sondos; Abidi, Kamel; Hammi, Yosra; Goucha, Rim; Naija, Ouns; Zarrouk, Chokri; Gargah, Tahar

2015-11-01

Rapidly progressive glomerulonephritis is a rare form of postinfectious glomerulonephritis. The aim of this study was to describe the outcome of our patients with severe post-streptococcal glomerulonephritis. This retrospective study was conducted in the department of pediatrics in Charles-Nicolle Hospital during a period of 13 years (1997-2009). Twenty-seven children were identified. The mean age was 8.7 years. All patients presented renal failure at presentation. The mean serum creatinine at presentation was 376.9 μmol/L. Six patients presented nephrotic syndrome. Twenty-six children had renal biopsies. Renal biopsies showed crescents in 24 cases. Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven patients required dialysis. At last follow-up, 22 patients (81.5%) had normal kidney function, 2 had renal dysfunction and 3 reached end stage renal disease. The only significant determinant for renal survival was the supportive dialysis (P=0.015). Rapidly progressive glomerulonephritis is uncommon. There have been significant advancements in supportive, as well as specific therapy, but the outcome continues to be poor. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons

DEFF Research Database (Denmark)

Kamara, David A; Nielsen, Lene Ryom; Ross, Michael

2014-01-01

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90ml/min/1.73m2 (using Cockcroft Gault) in the Data...

Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

Science.gov (United States)

Grilo, C. M.; White, M. A.; Wilson, G. T.; Gueorguieva, R.; Masheb, R. M.

2011-01-01

Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ≥70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment. PMID:21923964

Rapidly progressive glomerulonephritis in adolescents – aetiology and treatment based on case reports

Directory of Open Access Journals (Sweden)

Beata Banaszak

2017-06-01

Full Text Available Rapidly progressive glomerulonephritis is a disease characterised by an abrupt drop in glomerular filtration rate in a short period of time, which is caused by crescent formation seen in at least 50% of glomeruli. Two cases presented below illustrate rapid progressive glomerulonephritis in adolescents as a disease of heterogeneous aetiology that can develop both in the course of primary glomerulopathies and glomerulopathies secondary to systemic vasculitis. In the first case of an 11-year-old girl, nephritic syndrome with renal failure was accompanied by the presence of anti-myeloperoxidase antibodies in the serum, which in combination with the histopathological picture of the kidneys indicating pauci-immune rapidly progressive glomerulonephritis was the basis for the diagnosis of renal limited vasculitis. In the second case of a 16-year-old boy, an adverse course of acute post-streptococcal glomerulonephritis with features of severe and persistent glomerular filtration impairment was an indication for the verification of the diagnosis and identification of rapidly progressive glomerulonephritis based on a biopsy examination. Prompt diagnosis and inclusion of combined immunosuppressive therapy provided the chance to preserve renal function.

Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

Science.gov (United States)

Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

2015-01-12

We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Rapidly destructive osteoarthritis of the hip joint: a case series

Directory of Open Access Journals (Sweden)

McMurtrie A

2008-01-01

Full Text Available Abstract Background Rapidly destructive arthrosis of the hip is a rare and incompletely understood disorder with scarce literature about variations in natural history within a population. Methods A series of cases from North Wales with rapid progressive joint destruction and extensive subchondral bone loss in the femoral head and acetabulum are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities. Results Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average 14 months in 18 patients documented rapid hip destruction, involvement being unilateral in 13 cases. All patients underwent total hip arthroplasty, and osteoarthritis was confirmed at pathologic examination. Conclusion The authors postulate that these cases represent an uncommon subset of osteoarthritis and regular review, both clinically and radiologically, are required to assess speed of progression and prevent rapid loss of bone stock without the surgeon being aware. These cases are unsuitable for being placed on long waiting list due to technical difficulties in delayed surgery and compromised outcome following surgery.

Peranan Terapi Awal dan Terapi Pemeliharaan pada Rapidly Progressive Periodontitis Type 1

Directory of Open Access Journals (Sweden)

Anita H. Joedo

2015-08-01

Full Text Available Rapidly Progressive Periodontitis (RPP is a severe form of a periodontal disease which starts since a puberty age. The disease if a generalized periodontal destruction without a specific distribution mode: it develops more progressively but does not in accordance to local factors. The first step to the RPP treatment is initial therapy: i.e. DHE, scaling and root planing, and eliminating predisposing local factors and continued with a maintence therapy which will support the success of a surgery later. A study case: a 21-year old RPP woman showed hyperaemia, an abscess, a 10 mm mesial pocket depth, a 5 mm distal pocker depth, a 5 mm buccal pocket depth, a 2nd degree tooth mobility and a 3 mm buccal recession on 25. In the initial therapy she was given an amoxicillin, a metronidazole for killing a supra and subgingival baterial, vitamins B and C, and also a chlorhexidine 0.2% mouth wash for a week. After a week the abscess and the inflammation decreased, but the mobility was still in the same condition and the DHE was still evaluated because of the patient's social factor, the FO was delayed. The next visit was done every 2 monts for a year for maintenance care. The clinical result showed the gingival inflammation and the tooth mobility disappeared. Radiographically, the alveolar bone showed more radiopaque and the lamina dura was seen. In conclusio, the initial and the maintenance therapy was seen to heal the RPP.

Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

International Nuclear Information System (INIS)

Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

2007-01-01

Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

Hybrid antibiotics - clinical progress and novel designs.

Science.gov (United States)

Parkes, Alastair L; Yule, Ian A

2016-07-01

There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.

Rapid arc - clinical rationale and results

International Nuclear Information System (INIS)

Cozzi, Lucca

2008-01-01

The presentation will focus on the background of Intensity modulation volumetric arc therapy Rapid Arc from Varian Medical Systems aiming to highlight the technical and clinical rational also from an historical perspective to the founding pillars of fast delivery with a minimum number of arcs and a minimum number of monitor units

Rapidly aggravated Creutzfeldt-Jacob disease: autopsy-proven case

Energy Technology Data Exchange (ETDEWEB)

Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun [Seoul Veterans Hospital, Seoul (Korea, Republic of)

2005-11-15

Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images.

Rapidly aggravated Creutzfeldt-Jacob disease: autopsy-proven case

International Nuclear Information System (INIS)

Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun

2005-01-01

Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images

CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

Science.gov (United States)

Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

2015-03-01

Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

Science.gov (United States)

Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

2014-12-01

To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

Directory of Open Access Journals (Sweden)

Kikkawa Ryuichi

2004-12-01

Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.

Science.gov (United States)

Chow, Matthew; Cao, Michelle

2016-01-01

Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.

Modeling and Predicting AD Progression by Regression Analysis of Sequential Clinical Data

KAUST Repository

Xie, Qing

2016-02-23

Alzheimer\\'s Disease (AD) is currently attracting much attention in elders\\' care. As the increasing availability of massive clinical diagnosis data, especially the medical images of brain scan, it is highly significant to precisely identify and predict the potential AD\\'s progression based on the knowledge in the diagnosis data. In this paper, we follow a novel sequential learning framework to model the disease progression for AD patients\\' care. Different from the conventional approaches using only initial or static diagnosis data to model the disease progression for different durations, we design a score-involved approach and make use of the sequential diagnosis information in different disease stages to jointly simulate the disease progression. The actual clinical scores are utilized in progress to make the prediction more pertinent and reliable. We examined our approach by extensive experiments on the clinical data provided by the Alzheimer\\'s Disease Neuroimaging Initiative (ADNI). The results indicate that the proposed approach is more effective to simulate and predict the disease progression compared with the existing methods.

Modeling and Predicting AD Progression by Regression Analysis of Sequential Clinical Data

KAUST Repository

Xie, Qing; Wang, Su; Zhu, Jia; Zhang, Xiangliang

2016-01-01

Alzheimer's Disease (AD) is currently attracting much attention in elders' care. As the increasing availability of massive clinical diagnosis data, especially the medical images of brain scan, it is highly significant to precisely identify and predict the potential AD's progression based on the knowledge in the diagnosis data. In this paper, we follow a novel sequential learning framework to model the disease progression for AD patients' care. Different from the conventional approaches using only initial or static diagnosis data to model the disease progression for different durations, we design a score-involved approach and make use of the sequential diagnosis information in different disease stages to jointly simulate the disease progression. The actual clinical scores are utilized in progress to make the prediction more pertinent and reliable. We examined our approach by extensive experiments on the clinical data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results indicate that the proposed approach is more effective to simulate and predict the disease progression compared with the existing methods.

Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

Science.gov (United States)

Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

2015-03-01

Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Poorly differentiated ductal adenocarcinoma of the pancreas with rapid progression in a young man.

Science.gov (United States)

Tezuka, Koji; Ishiyama, Tomoharu; Takeshita, Akiko; Matsumoto, Hidekazu; Jingu, Akira; Kikuchi, Jiro; Yamaya, Hideyuki; Ohe, Rintaro; Ishizawa, Tetsuya

2018-04-16

Pancreatic cancer in young adults is very rare. We report a case of young-onset poorly differentiated pancreatic ductal adenocarcinoma with rapid progression and poor prognosis in a 31-year-old Japanese man with no obvious family history of malignancy. Preoperative examinations revealed a mass lesion in the body of the pancreas, accompanied by a slightly dilated main pancreatic duct distal to the mass lesion. Pancreatic cancer with acute pancreatitis was suspected because of an elevation of serum pancreatic enzyme and tumor marker, along with imaging findings. Distal pancreatectomy with resection of the common hepatic artery and splenectomy along with lymph node dissection was performed. Microscopically, the tumor was mainly composed of poorly differentiated ductal adenocarcinoma. The postoperative course was uneventful, but the patient had multiple liver metastases 2 months postoperatively, in spite of adjuvant chemotherapy, and died 8 months postoperatively. This case may represent a rare instance of young-onset poorly differentiated ductal adenocarcinoma with rapid progression and may indicate potential risk factors of pancreatic cancer in young adults.

EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease.

Science.gov (United States)

Freund, Brin; Probasco, John C; Cervenka, Mackenzie C; Sutter, Raoul; Kaplan, Peter W

2018-05-01

Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions.

The cost of implementing rapid HIV testing in sexually transmitted disease clinics in the United States.

Science.gov (United States)

Eggman, Ashley A; Feaster, Daniel J; Leff, Jared A; Golden, Matthew R; Castellon, Pedro C; Gooden, Lauren; Matheson, Tim; Colfax, Grant N; Metsch, Lisa R; Schackman, Bruce R

2014-09-01

Rapid HIV testing in high-risk populations can increase the number of persons who learn their HIV status and avoid spending clinic resources to locate persons identified as HIV infected. We determined the cost to sexually transmitted disease (STD) clinics of point-of-care rapid HIV testing using data from 7 public clinics that participated in a randomized trial of rapid testing with and without brief patient-centered risk reduction counseling in 2010. Costs included counselor and trainer time, supplies, and clinic overhead. We applied national labor rates and test costs. We calculated median clinic start-up costs and mean cost per patient tested, and projected incremental annual costs of implementing universal rapid HIV testing compared with current testing practices. Criteria for offering rapid HIV testing and methods for delivering nonrapid test results varied among clinics before the trial. Rapid HIV testing cost an average of US $22/patient without brief risk reduction counseling and US $46/patient with counseling in these 7 clinics. Median start-up costs per clinic were US $1100 and US $16,100 without and with counseling, respectively. Estimated incremental annual costs per clinic of implementing universal rapid HIV testing varied by whether or not brief counseling is conducted and by current clinic testing practices, ranging from a savings of US $19,500 to a cost of US $40,700 without counseling and a cost of US $98,000 to US $153,900 with counseling. Universal rapid HIV testing in STD clinics with same-day results can be implemented at relatively low cost to STD clinics, if brief risk reduction counseling is not offered.

Imaging findings and referral outcomes of rapid assessment stroke clinics

International Nuclear Information System (INIS)

Widjaja, E.; Manuel, D.; Hodgson, T.J.; Connolly, D.J.A.; Coley, S.C.; Romanowski, C.A.J.; Gaines, P.; Cleveland, T.; Thomas, S.; Griffiths, P.D.; Doyle, C.; Venables, G.S.

2005-01-01

AIM: A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. METHODS: Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. RESULTS: CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. CONCLUSION: Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated

Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

Science.gov (United States)

Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

2016-12-01

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Case report of a 28-year-old male with the rapid progression of steroid-resistant central nervous system vasculitis diagnosed by a brain biopsy.

Science.gov (United States)

Takahashi, Keigo; Sato, Hideki; Hattori, Hidenori; Takao, Masaki; Takahashi, Shinichi; Suzuki, Norihiro

2017-09-30

A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

International Nuclear Information System (INIS)

Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho; Suk, Eun Ha

2013-01-01

Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

Knowledge bases, clinical decision support systems, and rapid learning in oncology.

Science.gov (United States)

Yu, Peter Paul

2015-03-01

One of the most important benefits of health information technology is to assist the cognitive process of the human mind in the face of vast amounts of health data, limited time for decision making, and the complexity of the patient with cancer. Clinical decision support tools are frequently cited as a technologic solution to this problem, but to date useful clinical decision support systems (CDSS) have been limited in utility and implementation. This article describes three unique sources of health data that underlie fundamentally different types of knowledge bases which feed into CDSS. CDSS themselves comprise a variety of models which are discussed. The relationship of knowledge bases and CDSS to rapid learning health systems design is critical as CDSS are essential drivers of rapid learning in clinical care. Copyright © 2015 by American Society of Clinical Oncology.

Syndrome of rapid onset end stage renal disease in incident Mayo Clinic chronic hemodialysis patient

Directory of Open Access Journals (Sweden)

M. A. C. Onuigbo

2014-01-01

Full Text Available Despite decades of research, a full understanding of chronic kidney disease (CKD-end stage renal disease (ESRD progression remains elusive. The common consensus is a predictable, linear, progressive and time-dependent decline of CKD to ESRD. Acute kidney injury (AKI on CKD is usually assumed to be transient, with recovery as the expected outcome. AKI-ESRD association in current nephrology literature is blamed on the so-called "residual confounding." We had previously described a relationship between AKI events and rapid onset yet irreversible ESRD happening in a continuum in a high-risk CKD cohort. However, the contribution of the syndrome of rapid onset-ESRD (SORO-ESRD to incident United States ESRD population remained conjectural. In this retrospective analysis, we analyzed serum creatinine trajectories of the last 100 consecutive ESRD patients in 4 Mayo Clinic chronic hemodialysis units to determine the incidence of SORO-ESRD. Excluding 9 patients, 31 (34% patients, including two renal transplant recipients, had SORO-ESRD: 18 males and 13 females age 72 (range 50-92 years. Precipitating AKI followed pneumonia (8, acutely decompensated heart failure (7, pyelonephritis (4, post-operative (5, sepsis (3, contrast-induced nephropathy (2, and others (2. Time to dialysis was shortest following surgical procedures. Concurrent renin angiotensin aldosterone system blockade was higher with SORO-ESRD - 23% versus 5%, P = 0.0113. In conclusion, SORO-ESRD is not uncommon among the incident general US ESRD population. The implications for ESRD care planning, AV-fistula-first programs, general CKD care and any associations with renal ageing/senescence warrant further study.

Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated with Eribulin

NARCIS (Netherlands)

Van Hasselt, J. G C; Gupta, A.; Hussein, Z.; Beijnen, J. H.; Schellens, J. H M; Huitema, A. D R

2015-01-01

Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : the D:A:D study

NARCIS (Netherlands)

Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J; Schölvinck, Elisabeth H.

2014-01-01

BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

NARCIS (Netherlands)

Kamara, David A.; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Brandt, R. Salbøl; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundström, A.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.

2014-01-01

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

NARCIS (Netherlands)

Kamara, D.A.; Ryom, L.; Ross, M.; Kirk, O.; Reiss, P.; Morlat, P.; Moranne, O.; Fux, C.A.; Mocroft, A.; Sabin, C.; Lundgren, J.D.; Smith, C.J.; Koopmans †, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van; et al.,

2014-01-01

BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

Mycobacteria of clinical interest

International Nuclear Information System (INIS)

Casal, M.

1986-01-01

This book is based upon a symposium on mycobacteria of clinical interest. Due to the multidisciplinary participation of, among others, microbiologists, clinicians, immunologists and epidemiologists, a very wide and thorough presentation of the present state of clinical research in this field is ensured. Topics of particular interest included in this volume were the new antimicrobial agents active against mycobacteria; new therapeutic possibilities; a system of rapid diagnosis of tuberculosis and mycobacteriosis; mycobacteriosis in AIDS; progress in immunopathology of tuberculosis and leprosy; progress in bacteriology and vaccination in leprosy; progress in immunological diagnosis and new epidemiological biovars of M. tuberculosis. (Auth.)

Selfregulation – the key to progress in clinical reasoning

Directory of Open Access Journals (Sweden)

T Postma

2015-12-01

Full Text Available Background. In 2009 a new case-based instructional design was implemented during the preclinical year of study of the undergraduate dental curriculum of the University of Pretoria, South Africa. The objective of the educational intervention was to improve the development of clinical reasoning skills. To achieve this, systematic scaffolding, relevance, integration and problem-solving were actively promoted as part of teaching and learning. A student’s clinical reasoning was measured by a progress test containing 32 multiple choice questions (MCQs, formulated on a knowledge application level. In 2011 it became clear that some students showed progression while others did not. Objectives. This study was conducted to gauge the value of the case-based intervention with the aim of determining the need for further scaffolding and support, especially for non-progressing students. Methods. The 2011 BChD IV cohort (N=48 was identified for the study. Two semi-structured focus group discussions were conducted. Group 1 (n=8 consisted of students who progressed ≥9%, while group 2 (n=8 comprised students who did not progress to the same extent. Results. Both groups lauded the scaffolding that the case-based curriculum provided. Strategic thinking, goal orientation and self-regulation ability were identified in group 1. A lack of diligence, poor data-processing ability and a possible lack of interest were identified in group 2 students, who were unaware of learning opportunities. Conclusion. There is a need for early identification of students lacking self-regulated learning and for providing timely feedback and support to progressively develop their clinical reasoning skills.

The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress

Directory of Open Access Journals (Sweden)

Chow M

2016-03-01

Full Text Available Matthew Chow, Michelle CaoDepartment of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University School of Medicine, Stanford, CA, USAAbstract: Much of the understanding of the hypocretin/orexin (HCRT/OX system in sleep–wake regulation came from narcolepsy–cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively, as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep–wake control through complex interactions between monoaminergic/cholinergic (wake-promoting and gamma-aminobutyric acid-ergic (sleep-promoting neuronal systems. Deficiency of HCRT/OX results in loss of sleep–wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.Keywords: hypocretin, orexin, narcolepsy, insomnia, orexin antagonist, orexin agonist

Surgical treatment for progressive prostate cancer: A clinical case

Directory of Open Access Journals (Sweden)

E. I. Veliev

2014-01-01

Full Text Available In spite of its existing standards, the treatment of patients with progressive prostate cancer (PC remains a matter of debate. Ensuring that the patients have good quality of life is also relevant. The paper describes a clinical case of a patient with progressive PC after hormone therapy, brachytherapy, salvage prostatectomy, enucleation of the testicular parenchyma, and salvage lymphadenectomy. A phallic prosthesis and an artificial urinary sphincter have been implanted to improve quality of life. The results of preoperative examination and the technological features of surgical interventions are given.

Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Hai-yang JIANG

2017-10-01

Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

[Progress of midfacial fat compartments and related clinical applications].

Science.gov (United States)

Wen, Lihong; Wang, Jinhuang; Li, Yang; Liu, Dalie

2018-02-01

To review the research progress of midfacial fat compartments, and to thoroughly understand its current state of the anatomy and the aging morphologic characters of midfacial fat compartments, as well as the current status of clinical applications. The recent literature concerning the midfacial fat compartments and related clinical applications were extensively reviewed and analyzed. Midfacial fat layer has been considered as a fusion and a continuous layer, experiencing a global atrophy when aging. As more anatomical researches have done, recent studies have shown that midfacial fat layer is broadly divided into superficial and deep layers, which are both divided into different fat compartments by fascia, ligaments, or muscles. Midfacial fat compartments tend to atrophy with age, specifically in the deep fat compartments while hypertrophy in the superficial fat compartments. Clinical applications show that fat volumetric restoration with deep medial cheek fat and Ristow's space can restore the appearance of midface effectively. In recent years, the researches of midfacial fat compartments have achieved obvious progress, which will provide new ideas and basis for fat volumetric restoration. Corresponding treatments are selected based on different sites and different layers with different aging changes, reshaping a more youthful midface.

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Science.gov (United States)

Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

2017-04-15

Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Science.gov (United States)

Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

2015-01-01

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

Addressing unwarranted clinical variation: A rapid review of current evidence.

Science.gov (United States)

Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

2018-05-15

Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and

Nodal colloid goiter: clinical and morphological criteria of thyroid autonomy and progressive growth

Directory of Open Access Journals (Sweden)

S S Antonova

2006-03-01

Full Text Available Goal. To work up clinical and morphological criteria of thyroid authonomy and progressive growth in nodal colloid goiter (NCG. Methods. A group of patients with nodal euthyroid goiter (NEG (40 patients and a group of patients with nodular toxic goiter (NTG (40 patients were formed to compare clinical and morphological criteria of NCG growth to/with development of functional autonomy (FA. All patients were conducted research including physical examination, thyroid palpation, ultrasound, blood level of TSH and T4, scintigraphy, aspiration (needle biopsy, immunocytological and immunohistological reactions and statistics. In the study the method of indirect immunoperoxidase reaction with monoclonal rat/mouse antigens to Ki-67, TSH, galectin-3, Apo-test (“Dako Corporation”, “Novocastra Laboratories Ltd.” was used. Results. 1. In NEG expression of cell proliferation marker Ki-67 for certain rises pro rata to increase of proliferation degree, and in NTG grows according to FA development. 2. Apoptosis expression in NEG decreases according to degree of thyrocytes in a nodule, but in NTG falls pro rata to accumulation of thyroid FA. 3. Positive reaction for TSH in NEG tissue was found in 100%, whereas negative reaction for this receptor in NTG tissue was observed in 81% of all cases. 4. Galectin-3 was expressed in focuses of severe dysplasia of thyroid nodes tissue comparable to galectin-3 expression in the tissue of high-grade differentiated adenocarcinomas. Summary/conclusion. 1. Severe and moderate expression of Ki-67 and mild or negative immunomorphological reaction for Apo-test allows to refer such kinds of nodules to fast-growing/rapid-growing ones. 2. Reliable negative expression TSH receptor in the tissue of NCG is evidence of FA development and is an indication for a treatment of radioactive iodine or for an operation. 3. Galectin-3 probably is an early marker of malignant transformation in thyroid tissue. 4. Having conducted complex

HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

Science.gov (United States)

Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

2015-10-01

INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and

Successful Surgical Management of Retinopathy of Prematurity Showing Rapid Progression despite Extensive Retinal Photocoagulation.

Science.gov (United States)

Gadkari, Salil S; Kulkarni, Sucheta R; Kamdar, Rushita R; Deshpande, Madan

2015-01-01

The management of retinopathy of prematurity (ROP) can be challenging in preterm babies with a gestational age premature infant presented with "hybrid" zone 1 disease in the right eye and aggressive posterior ROP in the left eye. Both eyes were adequately treated with laser photocoagulation; however, the eyes deteriorated and progressed to stage 4 ROP. Both eyes eventually underwent intravitreal bevacizumab followed by lens sparing vitrectomy with good anatomical and visual outcome. Anticipation of progression despite laser photocoagulation in certain clinical scenarios, frequent follow-up and timely surgical intervention is paramount.

An unusual case of rapidly progressive contractures: Case report and brief review

Directory of Open Access Journals (Sweden)

Subasree R

2008-01-01

Full Text Available An 8-year-old boy, diagnosed as cervical dystonia, was referred to our tertiary center. After a trivial trauma he had developed painful lumps in the axial region, which was followed by restricted movements of neck, shoulder, and abdominal muscles over 4 months. He had kyphoscoliosis, torticollis, rigid abdomen, and multiple muscle contractures. He also had short great toes. A detailed skeletal survey showed calcification in the soft tissues surrounding the shoulder anterior chest wall, thorax, and paraspinal muscles; there was also beaking of vertebrae, which was confirmed by CT thorax. This report showcases the diagnostic challenge posed by myositis ossificans progressiva, which can rarely cause rapidly progressing muscle contractures. A brief review of literature is also presented.

Progressive learning in endoscopy simulation training improves clinical performance: a blinded randomized trial.

Science.gov (United States)

Grover, Samir C; Scaffidi, Michael A; Khan, Rishad; Garg, Ankit; Al-Mazroui, Ahmed; Alomani, Tareq; Yu, Jeffrey J; Plener, Ian S; Al-Awamy, Mohamed; Yong, Elaine L; Cino, Maria; Ravindran, Nikila C; Zasowski, Mark; Grantcharov, Teodor P; Walsh, Catharine M

2017-11-01

A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P PLC group had superior technical and communication skills and global performance in the simulated setting (P  .05). Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Rapidly progressive effusive constrictive pericarditis caused by methicillin sensitive Staphylococcus aureus (MSSA). samraakhtar@hotmail.com.

Science.gov (United States)

Akhtar, Naveed; Khalid, Ayesha; Ahmed, Waqas; Rasheed, Khalid

2010-04-01

Effusive-constrictive pericarditis is a clinical syndrome characterized by concurrent pericardial effusion and pericardial constriction, where constrictive hemodynamics are persistent after effusion is drained. It may present at any point along the clinical course, from the occurrence of an effusion to the development of chronic pericardial constriction. We refer an unusual case of effusive constrictive pericarditis developing rapidly within days, following purulent pericarditis secondary to chest trauma.

Predicting clinical decline in progressive agrammatic aphasia and apraxia of speech.

Science.gov (United States)

Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Clark, Heather M; Strand, Edythe A; Machulda, Mary M; Spychalla, Anthony J; Senjem, Matthew L; Jack, Clifford R; Josephs, Keith A

2017-11-28

To determine whether baseline clinical and MRI features predict rate of clinical decline in patients with progressive apraxia of speech (AOS). Thirty-four patients with progressive AOS, with AOS either in isolation or in the presence of agrammatic aphasia, were followed up longitudinally for up to 4 visits, with clinical testing and MRI at each visit. Linear mixed-effects regression models including all visits (n = 94) were used to assess baseline clinical and MRI variables that predict rate of worsening of aphasia, motor speech, parkinsonism, and behavior. Clinical predictors included baseline severity and AOS type. MRI predictors included baseline frontal, premotor, motor, and striatal gray matter volumes. More severe parkinsonism at baseline was associated with faster rate of decline in parkinsonism. Patients with predominant sound distortions (AOS type 1) showed faster rates of decline in aphasia and motor speech, while patients with segmented speech (AOS type 2) showed faster rates of decline in parkinsonism. On MRI, we observed trends for fastest rates of decline in aphasia in patients with relatively small left, but preserved right, Broca area and precentral cortex. Bilateral reductions in lateral premotor cortex were associated with faster rates of decline of behavior. No associations were observed between volumes and decline in motor speech or parkinsonism. Rate of decline of each of the 4 clinical features assessed was associated with different baseline clinical and regional MRI predictors. Our findings could help improve prognostic estimates for these patients. © 2017 American Academy of Neurology.

Rapid versus standard intravenous rehydration in paediatric gastroenteritis: pragmatic blinded randomised clinical trial

Science.gov (United States)

Parkin, Patricia C; Willan, Andrew R; Schuh, Suzanne

2011-01-01

Objective To determine if rapid rather than standard intravenous rehydration results in improved hydration and clinical outcomes when administered to children with gastroenteritis. Design Single centre, two arm, parallel randomised pragmatic controlled trial. Blocked randomisation stratified by site. Participants, caregivers, outcome assessors, investigators, and statisticians were blinded to the treatment assignment. Setting Paediatric emergency department in a tertiary care centre in Toronto, Canada. Participants 226 children aged 3 months to 11 years; complete follow-up was obtained on 223 (99%). Eligible children were aged over 90 days, had a diagnosis of dehydration secondary to gastroenteritis, had not responded to oral rehydration, and had been prescribed intravenous rehydration. Children were excluded if they weighed less than 5 kg or more than 33 kg, required fluid restriction, had a suspected surgical condition, or had an insurmountable language barrier. Children were also excluded if they had a history of a chronic systemic disease, abdominal surgery, bilious or bloody vomit, hypotension, or hypoglycaemia or hyperglycaemia. Interventions Rapid (60 mL/kg) or standard (20 mL/kg) rehydration with 0.9% saline over an hour; subsequent fluids administered according to protocol. Main outcome measures Primary outcome: clinical rehydration, assessed with a validated scale, two hours after the start of treatment. Secondary outcomes: prolonged treatment, mean clinical dehydration scores over the four hour study period, time to discharge, repeat visits to emergency department, adequate oral intake, and physician’s comfort with discharge. Data from all randomised patients were included in an intention to treat analysis. Results 114 patients were randomised to rapid rehydration and 112 to standard. One child was withdrawn because of severe hyponatraemia at baseline. There was no evidence of a difference between the rapid and standard rehydration groups in the

[Benefits of using rapid HIV testing at the PMU-FLON walk-in clinic in Lausanne].

Science.gov (United States)

Gilgien, W; Aubert, J; Bischoff, T; Herzig, L; Perdrix, J

2012-05-16

Lab tests are frequently used in primary care to guide patient care. This is particularly the case when a severe disorder, or one that will affect patients' initial care, needs to be excluded rapidly. At the PMU-FLON walk-in clinic the use of HIV testing as recommended by the Swiss Office of Public Health was hampered by the delay in obtaining test results. This led us to introduce rapid HIV testing which provides results within 30 minutes. Following the first 250 tests the authors discuss the results as well as the benefits of rapid HIV testing in an urban walk-in clinic.

Acute HIV infection with rapid progression to AIDS

Directory of Open Access Journals (Sweden)

Marcio de Oliveira Silva

Full Text Available Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

Rapidly progressive cryptogenic organising pneumonia presenting as a lung mass

Science.gov (United States)

Akram, Saeed; Irfan, Muhammad; Aftab, Kanwal

2009-01-01

A very rare case of a rapidly progressive variant of cryptogenic organising pneumonia (COP) presenting as a focal mass-like lesion with compression of the large airways leading to respiratory failure is described. A 60-year-old lady presented to the Aga Khan University Hospital Emergency Department in hypoxaemic respiratory failure with a 6-day history of dyspnoea, productive cough and fever. Chest x ray showed a right upper lobe mass-like lesion compressing the large airways and right pleural effusion. She deteriorated in the Emergency Department and was intubated due to worsening hypoxaemic respiratory failure. The pleural fluid and bronchoscopic specimens were negative on microbiological and cytological examination. CT-guided right lung biopsy revealed chronic non-specific inflammation without granuloma and malignancy. COP was diagnosed on video-assisted thoracoscopic (VATS) lung biopsy. She was successfully treated with high dose steroids and discharged in a stable condition; her 3-month follow-up chest x rays showed complete resolution of the lung lesion with some residual fibrosis. PMID:21686529

Rapid assessment breast clinics--evolution through audit.

Science.gov (United States)

Toomey, D P; Cahill, R A; Birido, N; Jeffers, M; Loftus, B; McInerney, D; Rothwell, J; Geraghty, J G

2006-11-01

This observational, cohort study aimed to examine the potential utility of Rapid Assessment Breast Clinics (RABC) beyond cancer detection at presentation. One thousand four hundred and twenty nine women were studied over an 18 month period. 154 (10.7%) had breast cancer - 87.7% of whom were seen expediently with 92.9% being diagnosed at one attendance. One hundred and forty three (10%) of those with a benign diagnosis were found by routine questioning to have significant familial risk separate to their reason for referral. Despite careful triage, considerable contamination of appointment allotment occurred with many who were correctly triaged as non-urgent being seen 'urgently'. One hundred and seventy six attendees (12.3%) had neither the symptom that triggered referral, nor breast lump, nipple discharge nor family history of breast cancer, while 283 (19.8%) had no objective clinical or radiological abnormality. Although RABC reliably categorise malignant versus non-malignant diagnoses despite cluttering by low risk women, a significant proportion of non-cancer patients still require address of future risk rather than reassurance of their present status alone.

Vascular Risk Factors and Clinical Progression in Spinocerebellar Ataxias

Directory of Open Access Journals (Sweden)

Raymond Y. Lo

2015-02-01

Full Text Available Background: The contributions of vascular risk factors to spinocerebellar ataxia (SCA are not known.Methods: We studied 319 participants with SCA 1, 2, 3, and 6 and repeatedly measured clinical severity using the Scale for Assessment and Rating of Ataxia (SARA for 2 years. Vascular risk factors were summarized by CHA2DS2-VASc scores as the vascular risk factor index. We employed regression models to study the effects of vascular risk factors on ataxia onset and progression after adjusting for age, sex, and pathological CAG repeats. Our secondary analyses took hyperlipidemia into account.Results: Nearly 60% of SCA participants were at low vascular risks with CHA2DS2-VASc = 0, and 31% scored 2 or greater. Higher CHA2DS2-VASc scores were not associated with either earlier onset or faster progression of ataxia. These findings were not altered after accounting for hyperlipidemia. Discussion: Vascular risks are not common in SCAs and are not associated with earlier onset or faster ataxia progression.

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

Progressive multifocal leukoencephalopathy. Epidemiology, clinical pictures, diagnosis and therapy

International Nuclear Information System (INIS)

Kishida, Shuji

2007-01-01

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of a ubiquitous polyomavirus JC (JCV). PML was for many years a rare disease occurring only in patients with underlying severe impaired immunity. Over the past three decades, the incidence of PML has significantly increased related to the AIDS (acquired immunodeficiency syndrome) pandemic and, more recently, to the growing use of immunosuppressive drugs. The clinical presentation of PML is variable with neurological symptoms corresponding to affected cerebral areas. Usually, the clinical outcome of patients with PML is poor with an inexorable progression to death within 6 months of symptom onset. Although PML usually requires a brain biopsy or autopsy for confirmation, radiological imaging and a demonstration of JCV-DNA in the CSF (cerebrospinal fluid) provide supportive evidence for the diagnosis. Although there is no proven effective therapy for PML, patients with HIV (human immunodeficeincy virus)-related PML may benefit significantly from HAART (highly active antiretroviral therapy). In this article the author reviews the epidemiology, especially in Japan, current challenges in the diagnosis and the treatment guidelines of patients with PML based on recent advances in the understanding of the JC virus biology. (author)

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

A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

Science.gov (United States)

Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

2018-03-20

Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

Science.gov (United States)

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P C: 1.32 (1.21, 1.45; P C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

Rapid application design of an electronic clinical skills portfolio for undergraduate medical students.

Science.gov (United States)

Dornan, Tim; Lee, Catherine; Stopford, Adam; Hosie, Liam; Maredia, Neil; Rector, Alan

2005-04-01

The aim was to find how to use information and communication technology to present the clinical skills content of an undergraduate medical curriculum. Rapid application design was used to develop the product, and technical action research was used to evaluate the development process. A clinician-educator, two medical students, two computing science masters students, two other project workers, and a hospital education informatics lead, formed a design team. A sample of stakeholders took part in requirements planning workshops and continued to advise the team throughout the project. A university hospital had many features that favoured fast, inexpensive, and successful system development: a clearly defined and readily accessible user group; location of the development process close to end-users; fast, informal communication; leadership by highly motivated and senior end-users; devolved authority and lack of any rigidly imposed management structure; cooperation of clinicians because the project drew on their clinical expertise to achieve scholastic goals; a culture of learning and involvement of highly motivated students. A detailed specification was developed through storyboarding, use case diagramming, and evolutionary prototyping. A very usable working product was developed within weeks. "SkillsBase" is a database web application using Microsoft Active Server Pages, served from a Microsoft Windows 2000 Server operating system running Internet Information Server 5.0. Graphing functionality is provided by the KavaChart applet. It presents the skills curriculum, provides a password-protected portfolio function, and offers training materials. The curriculum can be presented in several different ways to help students reflect on their objectives and progress towards achieving them. The reflective portfolio function is entirely private to each student user and allows them to document their progress in attaining skills, as judged by self, peer and tutor assessment, and

Milestones: a rapid assessment method for the Clinical Competency Committee

OpenAIRE

Nabors, Christopher; Forman, Leanne; Peterson, Stephen J.; Gennarelli, Melissa; Aronow, Wilbert S.; DeLorenzo, Lawrence; Chandy, Dipak; Ahn, Chul; Sule, Sachin; Stallings, Gary W.; Khera, Sahil; Palaniswamy, Chandrasekar; Frishman, William H.

2016-01-01

Introduction Educational milestones are now used to assess the developmental progress of all U.S. graduate medical residents during training. Twice annually, each program?s Clinical Competency Committee (CCC) makes these determinations and reports its findings to the Accreditation Council for Graduate Medical Education (ACGME). The ideal way to conduct the CCC is not known. After finding that deliberations reliant upon the new milestones were time intensive, our internal medicine residency pr...

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

Science.gov (United States)

Lammers, Twan; Kiessling, Fabian; Hennink, Wim E; Storm, Gert

2012-07-20

Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

A novel rapid access testicular cancer clinic: prospective evaluation after one year.

Science.gov (United States)

Carey, K; Davis, N F; Elamin, S; Ahern, P; Brady, C M; Sweeney, P

2016-02-01

Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). To present our experience after 12 months. All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.

Directory of Open Access Journals (Sweden)

Petra Steinacker

Full Text Available BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß correlated with clinical subtypes of ALS and were of prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study including patients with ALS (N = 68 with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20, and age-matched controls (N = 40, cerebrospinal fluid (CSF levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35 were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02 and with longer disease duration (p = 0.01 and p = 0.01, respectively. CSF NfH(SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01. High CSF NfH(SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively. The ratios CSF NfH(SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each. CSF Progranulin decreased with ongoing disease (p = 0.04. CONCLUSIONS: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP is linked to progressive neuro-axonal damage (increase of NfH(SMI35 and to progression of disease.

Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic.

Science.gov (United States)

Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

2015-10-19

Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. © 2015 The Author(s).

Current research on progressive familial intrahepatic cholestasis

Directory of Open Access Journals (Sweden)

DENG Baocheng

2015-09-01

Full Text Available Progressive familial intrahepatic cholestasis (PFIC refers to a heterogeneous group of autosomal-recessive disorders. The estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC-1, PFIC-2, and PFIC-3 are due to mutations in ATP8B1, ABCB11, and ABCB4 genes involved in bile secretion, respectively. Serum gamma-glutamyl transpeptidase is normal in patients with PFIC-1 and PFIC-2, while it is raised in patients with PFIC3. The main clinical manifestation of PFIC is severe intrahepatic cholestasis. PFIC usually appears in infancy or childhood and rapidly progresses to end-stage liver disease before adulthood. Diagnosis of this disease is based on clinical manifestations, liver function tests, liver ultrasonography, liver histology, and genetic testing. Ursodeoxycholic acid therapy is the initial treatment in all PFIC patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation.

Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia; Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom

Energy Technology Data Exchange (ETDEWEB)

Marienhagen, J.; Eilles, C. [Regensburg Univ. (Germany). Abt. fuer Nuklearmedizin; Weingaertner, U.; Blaha, L. [Bezirkskrankenhaus Mainkofen (Germany). Psychiatrische Klinik; Zerr, I.; Poser, S. [Goettingen Univ. (Germany). Klinik und Poliklinik fuer Neurologie

1999-07-01

We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [German] Wir berichten ueber einen 61jaehrigen Patienten mit progredientem dementiellen Syndrom, der unter der Verdachtsdiagnose einer Demenz vom Alzheimer-Typ (DAT) zur Hirn-SPECT-Untersuchung mit TC-99m-Bicisat (ECD) vorgestellt wurde. Zum Untersuchungszeitpunkt bestanden neben dem Vollbild einer Demenz eine ausgepraegte Apraxie und Aphasie bei unspezifischen Veraenderungen im EEG sowie der neuroradiologischen Bildgebung. In der Hirn-SPECT-Untersuchung fanden sich fuer eine DAT untypische ausgedehnte, vorwiegend rechtshemisphaerische Perfusionsstoerungen. Im weiteren Verlauf rasche Progredienz des Krankheitsbildes mit Entwicklung eines akinetischen Mutismus sowie Nachweis erhoehter Werte der neuronspezifischen Enolase und des 14-3-3-Proteins im Liquor. Der Patient verstarb schliesslich unter dem Bild einer Decortication. Aufgrund des klinischen Verlaufs sowie der Liquorbefunde wurde, da eine autoptische Befundsicherung

Rapidly Progressive Disseminated Sporotrichosis as the First Presentation of HIV Infection in a Patient with a Very Low CD4 Cell Count.

Science.gov (United States)

de Oliveira-Esteves, Isis Cristine Morávia Ribeiro; Almeida Rosa da Silva, Guilherme; Eyer-Silva, Walter de Araujo; Basílio-de-Oliveira, Rodrigo Panno; de Araujo, Luciana Ferreira; Martins, Carlos José; Neves-Motta, Rogério; Velho Mendes de Azevedo, Marcelo Costa; Signorini, Dario José Hart Pontes; Francisco da Cunha Pinto, Jorge; Moura, Lívia Machado; Laterça, Rafael Jacyntho; Pereira, Diogo Raphael Garcia de Oliveira; do Lago, Isabela Vieira; Raphael de Almeida Ferry, Fernando

2017-01-01

Sporotrichosis is a human and animal disease caused by species of the Sporothrix schenckii complex. It is classically acquired through traumatic inoculation of fungal elements. Most frequently, sporotrichosis presents as a fixed cutaneous or as a lymphocutaneous form. A much smaller number of cases occur as cutaneous disseminated and disseminated forms. These cases require immediate diagnosis and management to reduce morbidity and mortality. We present the case of a 34-year-old male patient in whom the first presentation of HIV infection was a rapidly progressive sporotrichosis with multiple cutaneous lesions, a high fungal burden in tissues, and pulmonary involvement. He had an extremely low CD4 cell count (06/mm 3 ). Treatment with amphotericin B deoxycholate led to complete clinical resolution. Sporotrichosis remains a neglected opportunistic infection among HIV-infected patients in Rio de Janeiro state, Brazil, and awareness of this potentially fatal infection is of utmost importance if treatment is not to be delayed and if potentially devastating complications are to be avoided.

Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape.

Science.gov (United States)

Emens, Leisha A; Ascierto, Paolo A; Darcy, Phillip K; Demaria, Sandra; Eggermont, Alexander M M; Redmond, William L; Seliger, Barbara; Marincola, Francesco M

2017-08-01

Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development. Current challenges facing the field include incorporating immunotherapy into adjuvant and neoadjuvant cancer therapy, refining dose, schedule and duration of treatment and developing novel surrogate endpoints that accurately capture overall survival benefit early in treatment. As the field rapidly evolves, we must prioritise the development of biomarkers to guide the use of immunotherapies in the most appropriate patients. Immunotherapy is already transforming cancer from a death sentence to a chronic disease for some patients. By making smart, evidence-based decisions in developing next generation immunotherapies, cancer should become an imminently treatable, curable and even preventable disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease

Directory of Open Access Journals (Sweden)

Jukka Lyytinen

2010-03-01

Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG. Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc.

Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

Energy Technology Data Exchange (ETDEWEB)

Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

2016-05-15

T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis.

Science.gov (United States)

Pérez Sánchez, S; Eichau Madueño, S; Rus Hidalgo, M; Domínguez Mayoral, A M; Vilches-Arenas, A; Navarro Mascarell, G; Izquierdo, G

2018-03-21

Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the 'as low as reasonably achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Disease progression was significantly correlated with ultrasound findings (P=.041 for the right eye and P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P=.07 for the right eye and P=.043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS). Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

Science.gov (United States)

Diomedi, Marina; Scacciatelli, Daria; Misaggi, Giulia; Balestrini, Simona; Balucani, Clotilde; Sallustio, Fabrizio; Di Legge, Silvia; Stanzione, Paolo; Silvestrini, Mauro

2014-01-01

This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

Directory of Open Access Journals (Sweden)

Simeone JC

2017-12-01

Full Text Available Jason C Simeone,1 Jay P Bae,2 Byron J Hoogwerf,3 Qian Li,1 Axel Haupt,3 Ayad K Ali,4 Marilyn K Boardman,3 Beth L Nordstrom1 1Real-world Evidence, Evidera, Waltham, MA, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Lily Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Global Patient Safety, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD and assess incidence and risk factors for disease progression in a retrospective study.Methods: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC, and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan–Meier plots and multistate models.Results: In the NAFLD cohort (N=18,754, 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM, and the mean body mass index was 38.2±10.2 kg/m2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression during follow-up (median=842 days. Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year.Conclusions: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of

Information needs for the rapid response team electronic clinical tool.

Science.gov (United States)

Barwise, Amelia; Caples, Sean; Jensen, Jeffrey; Pickering, Brian; Herasevich, Vitaly

2017-10-02

Information overload in healthcare is dangerous. It can lead to critical errors and delays. During Rapid Response Team (RRT) activations providers must make decisions quickly to rescue patients from physiological deterioration. In order to understand the clinical data required and how best to present that information in electronic systems we aimed to better assess the data needs of providers on the RRT when they respond to an event. A web based survey to evaluate clinical data requirements was created and distributed to all RRT providers at our institution. Participants were asked to rate the importance of each data item in guiding clinical decisions during a RRT event response. There were 96 surveys completed (24.5% response rate) with fairly even distribution throughout all clinical roles on the RRT. Physiological data including heart rate, respiratory rate, and blood pressure were ranked by more than 80% of responders as being critical information. Resuscitation status was also considered critically useful by more than 85% of providers. There is a limited dataset that is considered important during an RRT. The data is widely available in EMR. The findings from this study could be used to improve user-centered EMR interfaces.

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

Science.gov (United States)

Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

Psychiatric and clinical correlates of rapid cycling bipolar disorder: a cross-sectional study

Directory of Open Access Journals (Sweden)

Alexandre D. Gigante

2016-01-01

Full Text Available Objective: Rapid cycling (RC is a feature of bipolar disorder (BD that has been associated with worse outcome and more severe disability. Our goal was to investigate the association of demographic and clinical factors with RC. Methods: We compared RC and non-rapid cycling (NRC BD patients from the Brazilian Research Network in Bipolar Disorder (BRN-BD regarding age at onset of BD; total number of episodes; previous number of manic, depressive, mixed, and hypomanic episodes; polarity of the first episode; gender; number of suicide attempts; number of lifetime hospitalizations and lifetime history of at least one hospitalization; family history of mood disorder; clinical comorbidities such as hypothyroidism, hyperthyroidism, seizures; and current use of medications such as lithium, anticonvulsants, antipsychotics, and antidepressants. Results: We studied 577 patients and found that 100 (17.3% met the criteria for RC in the year before the investigation. RC patients had earlier age at onset, longer duration of disease, more lifetime depressive and manic episodes, higher number of suicide attempts, and higher rate antidepressant use. Conclusion: The presence of RC in the previous year was associated with specific clinical characteristics closely related to worse outcome in the course of BD.

The Clinical Observation on one case of Patient with Progressive Muscular Dystrophies

Directory of Open Access Journals (Sweden)

Yoo, Chang-Kil

2000-12-01

Full Text Available After observing a patient diagnosed with Progressive Muscular Dystropies from the August, 31, 2000 to the January, 2001, the following results are obtained. Method and Result: Under our assumption that the Korean Bee Venom Therapy is a good method to treat Progress Muscular Dystropies. Korean Bee Venom Therapy was applied on the following acupuncture points: BL23(Shinsu:腎兪, BL26(Guanyuanshu:關元兪, ST36(Chok-Samni:足三里, LI4(Hapkok:合谷, LV3(Taechung:太, SP10(Hyolhae:血海, SI9(Sojang-Kyonjong:貞. In addition CFC(Carthami Flos;紅花: and Cervi Pantotrichum Cornu; Herbal-Acupuncture is also treated on the other acupuncture points. For herbal medication was given to the patient based on the Sasang Constitution, Taeyangin Ogapijangchuk-tang. Following these treatments in this case of Progressive Muscular Dystropies, the skeletal muscle functions made remarkable improvement. Conclusion: Based on the clinical results, traditional Korean Medical treatment is believed to be effective for treating Progressive Muscular Dystropies, and further studies should be conducted to provide more valuable information.

Clinical advance in radionuclide imaging of pulmonary cancer

International Nuclear Information System (INIS)

Deng Zhiyong; Yang Lichun

2008-01-01

Radionuclide imaging of pulmonary cancer develops very rapidly in recent years. Its important value on the diagnosis, staging, monitoring recur and metastasis after treatment, and judging the curative effect and prognosis has been demonstrated. Clinicians pay more attention to it than before. This present article introduces the imaging principle, clinical use, good and bad points, progress situation of 67 Ga, 201 Tl, 99 Tc m , 18 F and their labelled compounds, which are more commonly used in clinical. And introduces the clinical progress of radionuclide imaging of pulmonary neoplasm concerning 99 Tc m -sestamibi ( 99 Tc m -MIBI), 99 Tc m -HL91 and 18 F-fluorodeoxyglucose ( 18 F-FDG) with emphasis. (authors)

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

Directory of Open Access Journals (Sweden)

Nan Wang

Full Text Available Type I diabetes (T1D, mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC transplantation. Older non-obese diabetic (NOD mice recipients (3m, at disease-onset stage receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage. FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg and lower proportion of proliferating T conventional cells (Tcon in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN, blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

Evaluation of the clinical utility of a rapid blood test for human leptospirosis

NARCIS (Netherlands)

Eapen, C. K.; Sugathan, Sheela; Kuriakose, Mariamma; Abdoel, Theresia; Smits, Henk L.

2002-01-01

A rapid assay device for the detection of Leptospira-specific immunoglobulin M (IgM) antibodies was applied on whole blood samples collected from a group of consecutive patients admitted with clinical suspicion of leptospirosis to a district hospital in Kerala, India. The hospital is located in an

Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy

Directory of Open Access Journals (Sweden)

Jesse A. Brown

2017-01-01

Full Text Available Progressive supranuclear palsy syndrome (PSP-S results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12 and healthy control subjects (n = 20 at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC, and parietal cortex (precuneus. Tf-fMRI functional connectivity (FC was examined in a rostral midbrain tegmentum (rMT-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum and posterior frontal (perirolandic cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP

Structural MRI correlates of amyotrophic lateral sclerosis progression.

Science.gov (United States)

Senda, Joe; Atsuta, Naoki; Watanabe, Hirohisa; Bagarinao, Epifanio; Imai, Kazunori; Yokoi, Daichi; Riku, Yuichi; Masuda, Michihito; Nakamura, Ryoichi; Watanabe, Hazuki; Ito, Mizuki; Katsuno, Masahisa; Naganawa, Shinji; Sobue, Gen

2017-11-01

Amyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain degeneration detected using structural MRI could reflect disease progression. On study registration, 3-Tesla volumetric MRI and diffusion tensor imaging scans were obtained at baseline in 38 healthy controls and 67 patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ≥36 and did not have the chromosome 9, open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R (ΔALSFRS-R) scores were calculated and patients were grouped into three categories, namely, patients with slow progression with ΔALSFRS-R scores ≤3 (n=19), intermediate progression with ΔALSFRS-R scores =4, 5 and 6 (n=36) and rapid progression with ΔALSFRS-R scores ≥7 (n=12). We analysed voxel-based morphometry and tract-based spatial statistics among these subgroups and controls. In comparison with controls, patients with ALS showed grey matter atrophy and decreased fractional anisotropy beyond the motor cortex and CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the degree of change was highly proportional to ΔALSFRS-R at the 6-month assessment. A more rapid disease progression and poorer functional decline were associated with greater involvement of the extra-motor cortex and basal ganglia, suggesting that the spatial extent of brain involvement can be an indicator of the progression in ALS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical inertia causing new or progression of diabetic retinopathy in type 2 diabetes: A retrospective cohort study.

Science.gov (United States)

Osataphan, Soravis; Chalermchai, Thep; Ngaosuwan, Kanchana

2017-03-01

Clinical inertia is a failure to intensify treatment according to evidence-based guidelines, and can have both short- and long-term adverse effects for type 2 diabetes (T2D). The aim of the present study was to demonstrate the effects of clinical inertia on glycemic control and diabetes-related complications. A retrospective cohort study was conducted at a university-based hospital in Thailand. Medical records were evaluated retrospectively from January 2010 to December 2014. Patients were classified into two groups: clinical inertia and non-inertia. Clinical inertia was defined as failure to initiate insulin within 3 months in patients with HbA1c ≥9 % who were already taking two oral antidiabetic agents. From 1206 records, 98 patients with mean HbA1c of 10.3 % were identified and enrolled in the study. The median follow-up time of these patients was 29.5 months and 68.4 % were classified into the clinical inertia group. The mean (± SD) HbA1c decrement in the clinical inertia and non-inertia groups was 0.82 ± 1.50 % and 3.02 ± 1.80 %, respectively, at 6 months (P inertia was associated with a significantly shorter median time to progression of diabetic retinopathy (DR); log rank test, P = 0.02 and a higher incidence of DR progression (10 vs 2.2 cases per 1000 person-months; P = 0.003). The adjusted incidence rate ratio for DR progression in the clinical inertia group was 4.92 (95 % confidence interval 1.11-21.77; P = 0.036). Being treated by general practitioners was the strongest risk factor associated with clinical inertia. Clinical inertia can cause persistently poor glycemic control and speed up the progression of DR in T2D. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

Directory of Open Access Journals (Sweden)

Subhamoy Pal

Full Text Available Early diagnosis of dengue virus (DENV infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1 has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs and enzyme-linked immunosorbent assays (ELISAs targeting NS1 antigen (Ag are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Retrospective samples from South America were used to evaluate the following tests: (i "Dengue NS1 Ag STRIP" and (ii "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France, (iii "Dengue NS1 Detect Rapid Test (1st Generation" and (iv "DENV Detect NS1 ELISA" (InBios International, United States, (v "Panbio Dengue Early Rapid (1st generation" (vi "Panbio Dengue Early ELISA (2nd generation" and (vii "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States. Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%.ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa.

Directory of Open Access Journals (Sweden)

Ziningi Jaya

Full Text Available Rapid HIV tests have improved access to HIV diagnosis and treatment by providing quick and convenient testing in rural clinics and resource-limited settings. In this study, we evaluated the quality management system for voluntary and provider-initiated point-of-care HIV testing in primary healthcare (PHC clinics in rural KwaZulu-Natal (KZN, South Africa.We conducted a quality assessment audit in eleven PHC clinics that offer voluntary HIV testing and counselling in rural KZN, South Africa from August 2015 to October 2016. All the participating clinics were purposively selected from the province-wide survey of diagnostic services. We completed an on-site monitoring checklist, adopted from the WHO guidelines for assuring accuracy and reliability of HIV rapid tests, to assess the quality management system for HIV rapid testing at each clinic. To determine clinic's compliance to WHO quality standards for HIV rapid testing the following quality measure was used, a 3-point scale (high, moderate and poor. A high score was defined as a percentage rating of 90 to 100%, moderate was defined as a percentage rating of 70 to 90%, and poor was defined as a percentage rating of less than 70%. Clinic audit scores were summarized and compared. We employed Pearson pair wise correlation coefficient to determine correlations between clinics audit scores and clinic and clinics characteristics. Linear regression model was computed to estimate statistical significance of the correlates. Correlations were reported as significant at p ≤0.05.Nine out of 11 audited rural PHC clinics are located outside 20Km of the nearest town and hospital. Majority (18.2% of the audited rural PHC clinics reported that HIV rapid test was performed by HIV lay counsellors. Overall, ten clinics were rated moderate, in terms of their compliance to the stipulated WHO guidelines. Audit results showed that rural PHC clinics' average rating score for compliance to the WHO guidelines ranged

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa.

Science.gov (United States)

Jaya, Ziningi; Drain, Paul K; Mashamba-Thompson, Tivani P

2017-01-01

Rapid HIV tests have improved access to HIV diagnosis and treatment by providing quick and convenient testing in rural clinics and resource-limited settings. In this study, we evaluated the quality management system for voluntary and provider-initiated point-of-care HIV testing in primary healthcare (PHC) clinics in rural KwaZulu-Natal (KZN), South Africa. We conducted a quality assessment audit in eleven PHC clinics that offer voluntary HIV testing and counselling in rural KZN, South Africa from August 2015 to October 2016. All the participating clinics were purposively selected from the province-wide survey of diagnostic services. We completed an on-site monitoring checklist, adopted from the WHO guidelines for assuring accuracy and reliability of HIV rapid tests, to assess the quality management system for HIV rapid testing at each clinic. To determine clinic's compliance to WHO quality standards for HIV rapid testing the following quality measure was used, a 3-point scale (high, moderate and poor). A high score was defined as a percentage rating of 90 to 100%, moderate was defined as a percentage rating of 70 to 90%, and poor was defined as a percentage rating of less than 70%. Clinic audit scores were summarized and compared. We employed Pearson pair wise correlation coefficient to determine correlations between clinics audit scores and clinic and clinics characteristics. Linear regression model was computed to estimate statistical significance of the correlates. Correlations were reported as significant at p ≤0.05. Nine out of 11 audited rural PHC clinics are located outside 20Km of the nearest town and hospital. Majority (18.2%) of the audited rural PHC clinics reported that HIV rapid test was performed by HIV lay counsellors. Overall, ten clinics were rated moderate, in terms of their compliance to the stipulated WHO guidelines. Audit results showed that rural PHC clinics' average rating score for compliance to the WHO guidelines ranged between 64.4% (CI

Factors that influence career progression among postdoctoral clinical academics: a scoping review of the literature

OpenAIRE

Ranieri, V.; Barratt, H.; Fulop, N.; Rees, G.

2016-01-01

Background: The future of academic medicine is uncertain. Concerns regarding the future availability of qualified and willing trainee clinical academics have been raised worldwide. Of significant concern is our failure to retain postdoctoral trainee clinical academics, who are likely to be our next generation of leaders in scientific discovery. / Objectives: To review the literature about factors that may influence postdoctoral career progression in early career clinical academics. / Design: ...

Factors that influence career progression among postdoctoral clinical academics: a scoping review of the literature

OpenAIRE

Ranieri, Veronica; Barratt, Helen; Fulop, Naomi; Rees, Geraint

2016-01-01

Background The future of academic medicine is uncertain. Concerns regarding the future availability of qualified and willing trainee clinical academics have been raised worldwide. Of significant concern is our failure to retain postdoctoral trainee clinical academics, who are likely to be our next generation of leaders in scientific discovery. Objectives To review the literature about factors that may influence postdoctoral career progression in early career clinical academics. Design This st...

Biomarkers in Scleroderma: Progressing from Association to Clinical Utility.

Science.gov (United States)

Ligon, Colin; Hummers, Laura K

2016-03-01

Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma's evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to benefit from specific therapies, and identify promising therapeutic targets for intervention. High-throughput technologies have recently identified fibrotic and inflammatory effectors in scleroderma that exhibit strong prognostic ability and may be tied to disease evolution. Increasingly, the use of collections of assayed circulating proteins and patterns of gene expression in tissue has replaced single-marker investigations in understanding the evolution of scleroderma and in objectively characterizing disease extent. Lastly, identification of shared patterns of disease evolution has allowed classification of patients into latent disease subtypes, which may allow rapid clinical prognostication and targeted management in both clinical and research settings. The concept of biomarkers in scleroderma is expanding to include nontraditional measures of aggregate protein signatures and disease evolution. This review examines the recent advances in biomarkers with a focus on those approaches poised to guide prospective management or themselves serve as quantitative surrogate disease outcomes.

Risks of rapid decline renal function in patients with type 2 diabetes

Institute of Scientific and Technical Information of China (English)

Yi-Jing; Sheen; Wayne; HH; Sheu

2014-01-01

Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general,it is defined by the decrease of estimated glomerular filtration rate(e GFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained declinein e GFR of > 5 m L/min per 1.73 m2 per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection.

Primary progressive apraxia of speech: clinical features and acoustic and neurologic correlates.

Science.gov (United States)

Duffy, Joseph R; Strand, Edythe A; Clark, Heather; Machulda, Mary; Whitwell, Jennifer L; Josephs, Keith A

2015-05-01

This study summarizes 2 illustrative cases of a neurodegenerative speech disorder, primary progressive apraxia of speech (AOS), as a vehicle for providing an overview of the disorder and an approach to describing and quantifying its perceptual features and some of its temporal acoustic attributes. Two individuals with primary progressive AOS underwent speech-language and neurologic evaluations on 2 occasions, ranging from 2.0 to 7.5 years postonset. Performance on several tests, tasks, and rating scales, as well as several acoustic measures, were compared over time within and between cases. Acoustic measures were compared with performance of control speakers. Both patients initially presented with AOS as the only or predominant sign of disease and without aphasia or dysarthria. The presenting features and temporal progression were captured in an AOS Rating Scale, an Articulation Error Score, and temporal acoustic measures of utterance duration, syllable rates per second, rates of speechlike alternating motion and sequential motion, and a pairwise variability index measure. AOS can be the predominant manifestation of neurodegenerative disease. Clinical ratings of its attributes and acoustic measures of some of its temporal characteristics can support its diagnosis and help quantify its salient characteristics and progression over time.

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

Science.gov (United States)

Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

2015-01-01

Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

Directory of Open Access Journals (Sweden)

Frank Y Ma

Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

Science.gov (United States)

Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

2017-03-09

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

Science.gov (United States)

Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

2017-01-01

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death

DEFF Research Database (Denmark)

Casadellà, Maria; Cozzi-Lepri, Alessandro; Phillips, Andrew

2017-01-01

OBJECTIVE: To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. DESIGN: Nested case-control study within the EuroSIDA cohort. METHODS: Cases were subjects with AIDS or who died from any cause...

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease.

Science.gov (United States)

Cholerton, Brenna; Johnson, Catherine O; Fish, Brian; Quinn, Joseph F; Chung, Kathryn A; Peterson-Hiller, Amie L; Rosenthal, Liana S; Dawson, Ted M; Albert, Marilyn S; Hu, Shu-Ching; Mata, Ignacio F; Leverenz, James B; Poston, Kathleen L; Montine, Thomas J; Zabetian, Cyrus P; Edwards, Karen L

2018-05-01

Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD. Copyright © 2018 Elsevier Ltd. All rights reserved.

MDS: Recent progress in molecular pathogenesis and clinical aspects.

Science.gov (United States)

Harada, Hironori

2017-01-01

Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

Assessing risk of fibrosis progression and liver-related clinical outcomes among patients with both early stage and advanced chronic hepatitis C.

Directory of Open Access Journals (Sweden)

Monica A Konerman

Full Text Available Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC. The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort.Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC, liver transplant (LT, HBV or HIV co-infection at presentation were analyzed (N = 1007. Outcomes included: 1 fibrosis progression 2 hepatic decompensation 3 HCC and 4 LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years.The external cohort had a median age of 49.4 years (IQR 44.3-54.3; 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2-7.6. Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2-7.6. Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73-0.83 and 0.76 (95% CI 0.69-0.81.Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases.

Frontiers of biostatistical methods and applications in clinical oncology

CERN Document Server

Crowley, John

2017-01-01

This book presents the state of the art of biostatistical methods and their applications in clinical oncology. Many methodologies established today in biostatistics have been brought about through its applications to the design and analysis of oncology clinical studies. This field of oncology, now in the midst of evolution owing to rapid advances in biotechnologies and cancer genomics, is becoming one of the most promising disease fields in the shift toward personalized medicine. Modern developments of diagnosis and therapeutics of cancer have also been continuously fueled by recent progress in establishing the infrastructure for conducting more complex, large-scale clinical trials and observational studies. The field of cancer clinical studies therefore will continue to provide many new statistical challenges that warrant further progress in the methodology and practice of biostatistics. This book provides a systematic coverage of various stages of cancer clinical studies. Topics from modern cancer clinical ...

Caries progression in non-cavitated fissures after infiltrant application: a 3-year follow-up of a randomized controlled clinical trial

Directory of Open Access Journals (Sweden)

Camillo ANAUATE-NETTO

Full Text Available Abstract Objectives To evaluate the efficacy of a conservative treatment to prevent the progression of caries using an infiltrant on non-cavitated pit and fissures. Material and Methods This controlled clinical trial selected 23 volunteers with clinically and radiographically non-cavitated occlusal caries among patients presenting a “rather low” to “very high” caries risk. Eighty-six teeth were randomly divided into two experimental groups: teeth receiving a commercial pit-and-fissure sealant (Alpha Seal-DFL and contralateral teeth receiving Icon infiltrant (DMG. Caries progression was monitored by clinical (laser fluorescence caries detection and radiographic examination at 12-month intervals over a period of 3 years of monitored caries progression. Probing the sealing materials to detect areas of retention was also used to evaluate marginal integrity. Results Statistical analysis showed no difference in caries progression using laser fluorescence caries detection when both materials were compared, regardless of the evaluation times (p>0.05. No significance was observed when the marginal sealant integrity of both materials was compared, regardless of the evaluation time (p0.05. SEM analysis exhibited a more homogeneous sealing for the infiltrant than obtained by the sealant. Conclusions The infiltrant was effective to prevent the caries progression in non-cavitated pit-and-fissures after 3 years of clinical evaluation, comparable with the conventional sealant. The infiltrant also presented better results in terms of caries progression at the 3-year evaluation time using the radiographic analysis.

Caries progression in non-cavitated fissures after infiltrant application: a 3-year follow-up of a randomized controlled clinical trial

Science.gov (United States)

ANAUATE-NETTO, Camillo; BORELLI, Laurindo; AMORE, Ricardo; DI HIPÓLITO, Vinicius; D’ALPINO, Paulo Henrique Perlatti

2017-01-01

Abstract Objectives To evaluate the efficacy of a conservative treatment to prevent the progression of caries using an infiltrant on non-cavitated pit and fissures. Material and Methods This controlled clinical trial selected 23 volunteers with clinically and radiographically non-cavitated occlusal caries among patients presenting a “rather low” to “very high” caries risk. Eighty-six teeth were randomly divided into two experimental groups: teeth receiving a commercial pit-and-fissure sealant (Alpha Seal-DFL) and contralateral teeth receiving Icon infiltrant (DMG). Caries progression was monitored by clinical (laser fluorescence caries detection) and radiographic examination at 12-month intervals over a period of 3 years of monitored caries progression. Probing the sealing materials to detect areas of retention was also used to evaluate marginal integrity. Results Statistical analysis showed no difference in caries progression using laser fluorescence caries detection when both materials were compared, regardless of the evaluation times (p>0.05). No significance was observed when the marginal sealant integrity of both materials was compared, regardless of the evaluation time (p0.05). SEM analysis exhibited a more homogeneous sealing for the infiltrant than obtained by the sealant. Conclusions The infiltrant was effective to prevent the caries progression in non-cavitated pit-and-fissures after 3 years of clinical evaluation, comparable with the conventional sealant. The infiltrant also presented better results in terms of caries progression at the 3-year evaluation time using the radiographic analysis. PMID:28877284

Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

Science.gov (United States)

Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

2017-04-01

We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

Rapid detection of Corynebacterium pseudotuberculosis in clinical samples from sheep.

Science.gov (United States)

Kumar, Jyoti; Tripathi, Bhupendra Nath; Kumar, Rajiv; Sonawane, Ganesh Gangaram; Dixit, Shivendra Kumar

2013-08-01

Corynebacterium pseudotuberculosis, a Gram-positive bacterium is the causative agent of caseous lymphadenitis (CLA), a chronic disease of sheep, goats and other warm blooded animals. In the present study, a total of 1,080 sheep reared under semi-intensive system on organized farms situated in the semi arid tropical region of Rajasthan, India, was clinically examined. Pus samples from superficial lymph nodes of 25 (2.31%) adult sheep showing clinical lesions similar to CLA were collected for laboratory analyses. On the basis of morphological, cultural and biochemical characteristics 12 (48%) bacterial isolates from pus identified it as C. pseudotuberculosis. A polymerase chain reaction (PCR) assay targeting Putative oligopeptide/dipeptide ABC transporter, nicotinamide adenine dinucleotide phosphate (NADP) oxidoreductase coenzyme F420-dependent and proline iminopeptidase (PIP) genes of C. pseudotuberculosis was developed that showed 14 pus samples as positive. All C. pseudotuberculosis isolates were also found positive for these genes in the PCR. The specificity of the PCR products was confirmed by sequencing of the amplified products that showed 98-100% homology with published sequences available in the NCBI database. The present study shows the incidence of CLA as 2.31%, 1.1% and 1.29% based on clinical, bacterial culture and direct pus PCR assay, respectively. The PCR assay was rapid, specific and as significant as bacterial culture in detecting bacteria directly in the clinical pus samples. The PCR assay developed in the study can be applied for the diagnosis and control of CLA. Furthermore, the assay can also be applied to detect C. pseudotuberculosis in various clinical samples.

Recent progress in ERCP for biliary and pancreatic diseases

Directory of Open Access Journals (Sweden)

MIAO Lin

2014-12-01

Full Text Available In recent years, with the continuous development of endoscopic and interventional techniques, many new devices and methods have been used in clinical practice, and the application of endoscopic retrograde cholangiopancreatography (ERCP in biliary and pancreatic diseases has developed rapidly. This paper reviews and summarizes the recent progress in ERCP among patients with biliary and pancreatic diseases, including those with altered gastrointestinal anatomy, pregnant patients, patients with benign and malignant biliary strictures, and patients with pancreatic pseudocysts, as well as the application of SpyGlass, photodynamic therapy, and radiofrequency ablation, the management of ERCP-related duodenal perforation, and the prevention of post-ERCP pancreatitis. All the progress has made a great contribution to the diagnosis and treatment of biliary and pancreatic diseases.

Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

Science.gov (United States)

Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

2015-09-29

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

Advances in developing rapid, reliable and portable detection systems for alcohol.

Science.gov (United States)

Thungon, Phurpa Dema; Kakoti, Ankana; Ngashangva, Lightson; Goswami, Pranab

2017-11-15

Development of portable, reliable, sensitive, simple, and inexpensive detection system for alcohol has been an instinctive demand not only in traditional brewing, pharmaceutical, food and clinical industries but also in rapidly growing alcohol based fuel industries. Highly sensitive, selective, and reliable alcohol detections are currently amenable typically through the sophisticated instrument based analyses confined mostly to the state-of-art analytical laboratory facilities. With the growing demand of rapid and reliable alcohol detection systems, an all-round attempt has been made over the past decade encompassing various disciplines from basic and engineering sciences. Of late, the research for developing small-scale portable alcohol detection system has been accelerated with the advent of emerging miniaturization techniques, advanced materials and sensing platforms such as lab-on-chip, lab-on-CD, lab-on-paper etc. With these new inter-disciplinary approaches along with the support from the parallel knowledge growth on rapid detection systems being pursued for various targets, the progress on translating the proof-of-concepts to commercially viable and environment friendly portable alcohol detection systems is gaining pace. Here, we summarize the progress made over the years on the alcohol detection systems, with a focus on recent advancement towards developing portable, simple and efficient alcohol sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

A rapid two-step algorithm detects and identifies clinical macrolide and beta-lactam antibiotic resistance in clinical bacterial isolates.

Science.gov (United States)

Lu, Xuedong; Nie, Shuping; Xia, Chengjing; Huang, Lie; He, Ying; Wu, Runxiang; Zhang, Li

2014-07-01

Aiming to identify macrolide and beta-lactam resistance in clinical bacterial isolates rapidly and accurately, a two-step algorithm was developed based on detection of eight antibiotic resistance genes. Targeting at genes linked to bacterial macrolide (msrA, ermA, ermB, and ermC) and beta-lactam (blaTEM, blaSHV, blaCTX-M-1, blaCTX-M-9) antibiotic resistances, this method includes a multiplex real-time PCR, a melting temperature profile analysis as well as a liquid bead microarray assay. Liquid bead microarray assay is applied only when indistinguishable Tm profile is observed. The clinical validity of this method was assessed on clinical bacterial isolates. Among the total 580 isolates that were determined by our diagnostic method, 75% of them were identified by the multiplex real-time PCR with melting temperature analysis alone, while the remaining 25% required both multiplex real-time PCR with melting temperature analysis and liquid bead microarray assay for identification. Compared with the traditional phenotypic antibiotic susceptibility test, an overall agreement of 81.2% (kappa=0.614, 95% CI=0.550-0.679) was observed, with a sensitivity and specificity of 87.7% and 73% respectively. Besides, the average test turnaround time is 3.9h, which is much shorter in comparison with more than 24h for the traditional phenotypic tests. Having the advantages of the shorter operating time and comparable high sensitivity and specificity with the traditional phenotypic test, our two-step algorithm provides an efficient tool for rapid determination of macrolide and beta-lactam antibiotic resistances in clinical bacterial isolates. Copyright © 2014 Elsevier B.V. All rights reserved.

Defining natural history: assessment of the ability of college students to aid in characterizing clinical progression of Niemann-Pick disease, type C.

Directory of Open Access Journals (Sweden)

Jenny Shin

Full Text Available Niemann-Pick Disease, type C (NPC is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.

Monitoring progression of clinical reasoning skills during health sciences education using the case method - a qualitative observational study.

Science.gov (United States)

Orban, Kristina; Ekelin, Maria; Edgren, Gudrun; Sandgren, Olof; Hovbrandt, Pia; Persson, Eva K

2017-09-11

Outcome- or competency-based education is well established in medical and health sciences education. Curricula are based on courses where students develop their competences and assessment is also usually course-based. Clinical reasoning is an important competence, and the aim of this study was to monitor and describe students' progression in professional clinical reasoning skills during health sciences education using observations of group discussions following the case method. In this qualitative study students from three different health education programmes were observed while discussing clinical cases in a modified Harvard case method session. A rubric with four dimensions - problem-solving process, disciplinary knowledge, character of discussion and communication - was used as an observational tool to identify clinical reasoning. A deductive content analysis was performed. The results revealed the students' transition over time from reasoning based strictly on theoretical knowledge to reasoning ability characterized by clinical considerations and experiences. Students who were approaching the end of their education immediately identified the most important problem and then focused on this in their discussion. Practice knowledge increased over time, which was seen as progression in the use of professional language, concepts, terms and the use of prior clinical experience. The character of the discussion evolved from theoretical considerations early in the education to clinical reasoning in later years. Communication within the groups was supportive and conducted with a professional tone. Our observations revealed progression in several aspects of students' clinical reasoning skills on a group level in their discussions of clinical cases. We suggest that the case method can be a useful tool in assessing quality in health sciences education.

Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.

Directory of Open Access Journals (Sweden)

Bulbulgul Aumakhan

Full Text Available BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004, an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001 and 51 to 101 reduced CD4+ T cells/mm(3 over time compared to asymptomatic HSV-2 infection (trend p<0.001. CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.

Recent progress in the clinical application of partial splenic embolization

International Nuclear Information System (INIS)

Zhou Yaojun; Liu Changjiang; Wang Yaojun

2012-01-01

Partial splenic embolization (PSE) is a non-surgical procedure used to treat hypersplenism in various clinical settings and thus to avoid the disadvantages of splenectomy. PSE can be employed for the treatment of a variety of diseases including hypersplenism, thrombocytopenia, portal hypertension, splenic arterial aneurysms, etc. PSE can effectively relieve the splenic artery steal syndrome which occurred after liver transplantation, and therefore significantly improve the blood perfusion of the recipient liver. Besides, PSE can also be adopted to reduce the bleeding risk in patients with esophageal and gastric varices caused by portal hypertension. PSE is beneficial to the improvement of peripheral hematologic parameters, which helps the patients successfully undergo the high-dose chemotherapy or interferon therapy. In addition, PSE possesses potential curative effect for thrombocytopenia related diseases such as chronic idiopathic thrombocytopenic purpura. This paper aims to make a comprehensive review of the recent progress in the clinical application of partial splenic embolization. (authors)

Provider-related barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs) and hospitals.

Science.gov (United States)

Bogart, Laura M; Howerton, Devery; Lange, James; Setodji, Claude Messan; Becker, Kirsten; Klein, David J; Asch, Steven M

2010-06-01

We examined provider-reported barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs), and hospitals. 12 primary metropolitan statistical areas (PMSAs; three per region) were sampled randomly, with sampling weights proportional to AIDS case reports. Across PMSAs, all 671 hospitals and a random sample of 738 clinics/CBOs were telephoned for a survey on rapid HIV test availability. Of the 671 hospitals, 172 hospitals were randomly selected for barriers questions, for which 158 laboratory and 136 department staff were eligible and interviewed in 2005. Of the 738 clinics/CBOs, 276 were randomly selected for barriers questions, 206 were reached, and 118 were eligible and interviewed in 2005-2006. In multivariate models, barriers regarding translation of administrative/quality assurance policies into practice were significantly associated with rapid HIV testing availability. For greater rapid testing diffusion, policies are needed to reduce administrative barriers and provide quality assurance training to non-laboratory staff.

Previously Unidentified Single Nucleotide Polymorphisms in HIV/AIDS Cases Associate with Clinical Parameters and Disease Progression

Directory of Open Access Journals (Sweden)

Vladimir V. Anokhin

2016-01-01

Full Text Available The genetic background of an individual plays an important role in the progression of HIV infection to AIDS. Identifying previously unknown or uncharacterized single nucleotide polymorphisms (SNPs that associate with disease progression may reveal important therapeutic targets and provide a greater understanding of disease pathogenesis. In the present study, we employed ultra-high multiplex PCR on an Ion Torrent next-generation sequencing platform to sequence 23 innate immune genes from 94 individuals with HIV/AIDS. This data was used to identify potential associations of SNPs with clinical parameters and disease progression. SNPs that associated with an increased viral load were identified in the genes for the interleukin 15 receptor (IL15RA, toll-like receptor 7 (TLR7, tripartite motif-containing protein 5 (TRIM5, and two killer-cell immunoglobulin-like receptors (KIR2DL1 and KIR2DL3. Additionally, SNPs that associated with progression from HIV infection to AIDS were identified in two 2′-5′-oligoadenylate synthetase genes (OAS2 and OAS3. In contrast, other SNPs identified in OAS2 and OAS3 genes, as well as in the TRIM5 and KIR2DS4 genes, were associated with a slower progression of disease. Taken together, our data demonstrates the utility of ultra-high multiplex PCR in identifying polymorphisms of potential clinical significance and further,identifies SNPs that may play a role in HIV pathogenesis.

Clinical features of Parkinson’s disease with and without rapid eye movement sleep behavior disorder

OpenAIRE

Liu, Ye; Zhu, Xiao-Ying; Zhang, Xiao-Jin; Kuo, Sheng-Han; Ondo, William G.; Wu, Yun-Cheng

2017-01-01

Background Rapid eye movement sleep behavior disorder (RBD) and Parkinson’s disease (PD) are two distinct clinical diseases but they share some common pathological and anatomical characteristics. This study aims to confirm the clinical features of RBD in Chinese PD patients. Methods One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in  Department of Neurology, Shanghai General Hospital from January 2013 to August 2014. This study examined P...

50 years of pediatric immunology: progress and future, a clinical perspective.

Science.gov (United States)

Singh, Surjit; Gupta, Anju; Rawat, Amit

2013-01-08

Rapidly evolving advances in the field of immunology over the last few decades have impacted the practice of clinical medicine in many ways. In fact, understanding the immunological basis of disease has been pivotal in deciphering the pathogenesis of several disease processes, infective or otherwise. As of today, there is hardly any specialty of medicine which is not influenced by immunology. Pediatric rheumatological disorders, vasculitides, Human Immunodeficiency Virus (HIV) infection, Primary Immunodeficiency Diseases (PIDs) and autoimmune disorders fall under the domain of clinical immunology. This specialty is poised to emerge as a major clinical specialty in our country. The gulf between bench and bedside is narrowing down as our understanding of the complex immunological mechanisms gets better. However, a lot still needs to be done in this field as the morbidity and mortality of some of these conditions is unacceptably high in the Indian setup. A number of medical schools and institutes in the country now have the resources and the wherewithal to develop into specialized centres of clinical immunology. We need to concentrate on training more physicians and pediatricians in this field. The future is bright and the prospects exciting.

Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial.

Science.gov (United States)

Silva, Marly Conceição; Magalhães, Tiago Augusto; Meira, Zilda Maria Alves; Rassi, Carlos Henrique Reis Esselin; Andrade, Amanda Cristina de Souza; Gutierrez, Paulo Sampaio; Azevedo, Clerio Francisco; Gurgel-Giannetti, Juliana; Vainzof, Mariz; Zatz, Mayana; Kalil-Filho, Roberto; Rochitte, Carlos Eduardo

2017-02-01

In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival. To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR). A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non-intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016. Randomization (1:1) to receive or not receive ACE inhibitor therapy. Primary outcome was MF progression from baseline to the 2-year CMR study. Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], -0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], -4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04

Genetics of Progressive Supranuclear Palsy

Directory of Open Access Journals (Sweden)

Sun Young Im

2015-09-01

Full Text Available Progressive supranuclear palsy (PSP is a neurodegenerative syndrome that is clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism and cognitive decline. Pathologically, diagnosis of PSP is based on characteristic features, such as neurofibrillary tangles, neutrophil threads, tau-positive astrocytes and their processes in basal ganglia and brainstem, and the accumulation of 4 repeat tau protein. PSP is generally recognized as a sporadic disorder; however, understanding of genetic background of PSP has been expanding rapidly. Here we review relevant publications to outline the genetics of PSP. Although only small number of familial PSP cases have been reported, the recognition of familial PSP has been increasing. In some familial cases of clinically probable PSP, PSP pathologies were confirmed based on NINDS neuropathological diagnostic criteria. Several mutations in MAPT, the gene that causes a form of familial frontotemporal lobar degeneration with tauopathy, have been identified in both sporadic and familial PSP cases. The H1 haplotype of MAPT is a risk haplotype for PSP, and within H1, a sub-haplotype (H1c is associated with PSP. A recent genome-wide association study on autopsyproven PSP revealed additional PSP risk alleles in STX6 and EIF2AK3. Several heredodegenerative parkinsonian disorders are referred to as PSP-look-alikes because their clinical phenotype, but not their pathology, mimics PSP. Due to the fast development of genomics and bioinformatics, more genetic factors related to PSP are expected to be discovered. Undoubtedly, these studies will provide a better understanding of the pathogenesis of PSP and clues for developing therapeutic strategies.

Development and clinical evaluation of a rapid diagnostic kit for feline leukemia virus infection.

Science.gov (United States)

Kim, Won-Shik; Chong, Chom-Kyu; Kim, Hak-Yong; Lee, Gyu-Cheol; Jeong, Wooseog; An, Dong-Jun; Jeoung, Hye-Young; Lee, Jae-In; Lee, Young-Ki

2014-01-01

Feline leukemia virus (FeLV) causes a range of neoplastic and degenerative diseases in cats. To obtain a more sensitive and convenient diagnosis of the disease, we prepared monoclonal antibodies specific for the FeLV p27 to develop a rapid diagnostic test with enhanced sensitivity and specificity. Among these antibodies, we identified two clones (hybridomas 8F8B5 and 8G7D1) that specifically bound to FeLV and were very suitable for a diagnostic kit. The affinity constants for 8F8B5 and 8G7D1 were 0.35 × 10⁸ and 0.86 × 10⁸, respectively. To investigate the diagnostic abilities of the rapid kit using these antibodies, we performed several clinical studies. Assessment of analytical sensitivity revealed that the detection threshold of the rapid diagnostic test was 2 ng/mL for recombinant p27 and 12.5 × 10⁴ IU/mL for FeLV. When evaluating 252 cat sera samples, the kit was found to have a kappa value of 0.88 compared to polymerase chain reaction (PCR), indicating a significant correlation between data from the rapid diagnostic test and PCR. Sensitivity and specificity of the kit were 95.2% (20/21) and 98.5% (257/261), respectively. Our results demonstrated that the rapid diagnostic test would be a suitable diagnostic tool for the rapid detection of FeLV infection in cats.

Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case report

Directory of Open Access Journals (Sweden)

Rais Ghizlane

2012-04-01

Full Text Available Abstract Introduction Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult. Case presentation A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. Conclusions Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified.

Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

OpenAIRE

Brown-Elliott, Barbara A.; Wallace, Richard J.

2002-01-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on ...

MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive nonfluent aphasia.

Science.gov (United States)

Allegri, Ricardo F; Bartoloni, Leonardo; Iturry, Mónica; Romero, Carlos; Begué, Christián; Sevlever, Gustavo; Taratuto, Ana Lía

2014-01-01

We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype by histotyping.

Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

Science.gov (United States)

Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

2016-01-01

Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects.

Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech

Directory of Open Access Journals (Sweden)

Jennifer L. Whitwell

2016-01-01

Full Text Available Beta-amyloid (Aβ deposition can be observed in primary progressive aphasia (PPA and progressive apraxia of speech (PAOS. While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified and PAOS (n = 42 subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+ status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+ status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+ status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified

Rapid gated Thallium-201 perfusion SPECT - clinically feasible?

International Nuclear Information System (INIS)

Wadhwa, S.S.; Mansberg, R.; Fernandes, V.B.; Wilkinson, D.; Abatti, D.

1998-01-01

Full text: Standard dose energy window optimised Thallium-201 (Tl-201) SPECT has about half the counts of a standard dose from Technetium-99m Sestamibi (Tc99m-Mibi) gated perfusion SPECT. This study investigates the clinical feasibility of rapid energy window optimised Tl-201 gated perfusion SPECT (gated-TI) and compares quantitative left ventricular ejection fraction (LVEF) and visually assessed image quality for wall motion and thickening to analogous values obtained from Tc99m-Mibi gated perfusion SPECT (gated - mibi). Methods: We studied 60 patients with a rest gated Tl-201 SPECT (100 MBq, 77KeV peak, 34% window, 20 sec/projection) followed by a post stress gated Sestamibi SPECT (1GBq, 140KeV, 20% window, 20 sec/projection) separate dual isotope protocol. LVEF quantitation was performed using commercially available software (SPECTEF, General Electric). Visual grading of image quality for wall thickening and motion was performed using a three-point scale (excellent, good and poor). Results: LVEF for gated Tl-201 SPECT was 59.6 ± 12.0% (Mean ± SD). LVEF for gated Sestamibi SPECT was 60.4 ±11.4% (Mean ± SD). These were not significantly different (P=0.27, T-Test). There was good correlation (r=0.9) between gated-TI and gated-mibi LVEF values. The quality of gated-Tl images was ranked as excellent, good and poor in 12, 50 and 38% of the patients respectively. Image quality was better in gated-mibi SPECT, with ratings of 12, 62 and 26% respectively. Conclusion: Rapid gated Thallium-201 acquisition with energy window optimisation can be effectively performed on majority of patients and offers the opportunity to assess not only myocardial perfusion and function, as with Technetium based agents, but also viability using a single day one isotope protocol

Progress study of the cardiac damage in Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

ZHANG Yao

2013-05-01

Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, as well as early prevention and treatment of DMD.

Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease.

Science.gov (United States)

Hayase, Tomomi; Shimizu, Jun; Goto, Tamako; Nozaki, Yasuyuki; Mori, Masato; Takahashi, Naoto; Namba, Eiji; Yamagata, Takanori; Momoi, Mariko Y

2010-03-01

We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.

Correlation between clinical fetal head station and sonographic angle of progression during the second stage of labor.

Science.gov (United States)

Perlman, Sharon; Kivilevitch, Zvi; Moran, Orit; Katorza, Eldad; Kees, Salim; Achiron, Reuven; Gilboa, Yinon

2017-08-04

To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range. A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed. Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r 2  = 0.423, p correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor.

Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern.

Directory of Open Access Journals (Sweden)

Moisés Selman

Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is characterized by the insidious onset of dyspnea or cough. However, a subset of patients has a short duration of symptoms with rapid progression to end-stage disease. In this study, we evaluated clinical and molecular features of "rapid" and "slow" progressors with IPF. METHODS AND FINDINGS: 26 patients with 24 months of symptoms [slow progressors] were studied. Survival was analyzed by the Kaplan-Meyer method and proportional hazard's model. Lung microarrays and tissue proteins were measured in a subset of patients. No differences were found in age, physiologic impairment and bronchoalveolar lavage (BAL cellular profile. There were more males (OR = 6.5; CI:1.4-29.5; p = 0.006 and smokers (OR = 3.04; CI:1.1-8.3; p = 0.04 in the rapid progressors group. Survival from the beginning of symptoms was significantly reduced in rapid progressors (HR = 9.0; CI:4.48-18.3; p2-fold increase of active matrix metalloproteinase-9, and induced a higher fibroblast migration compared with slow progressors and controls [238+/-98% versus 123+/-29% (p<0.05 and 30+/-17% (p<0.01]. CONCLUSIONS/SIGNIFICANCE: A subgroup of IPF patients, predominantly smoking males, display an accelerated clinical course and have a gene expression pattern that is different from those with slower progression and longer survival. These findings highlight the variability in the progression of IPF, and may explain, in part, the difficulty in obtaining significant and reproducible results in studies of therapeutic interventions in patients with IPF.

Microbiological characteristics of subgingival microbiota in adult periodontitis, localized juvenile periodontitis and rapidly progressive periodontitis subjects.

Science.gov (United States)

Nonnenmacher, C; Mutters, R; de Jacoby, L F

2001-04-01

To describe the prevalence of the cultivable subgingival microbiota in periodontal diseases and to draw attention to the polymicrobial nature of periodontic infections. The study population consisted of 95 patients, 51 females and 44 males, aged 14-62 years. Twenty-nine patients exhibited adult periodontitis (AP), six localized juvenile periodontitis (LJP), and 60 rapidly progressive periodontitis (RPP). Two to four pooled bacterial samples were obtained from each patient. Samples were collected with sterile paper points from the deepest periodontal pockets. The samples were cultured under anaerobic and microaerophilic conditions using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and by a commercial rapid test system. Prevotella intermedia and Capnocytophaga spp. were the most frequently detected microorganisms in all diagnostic groups. Porphyromonas gingivalis and Peptostreptococcus micros were found more frequently in AP and RPP patients, while Actinobacillus actinomycetemcomitans and Eikenella corrodens were associated with AP, LJP and RPP patients. The other bacterial species, including Actinomyces spp., Streptococcus spp. and Eubacterium spp., were detected at different levels in the three disease groups. The data show the complexity of the subgingival microbiota associated with different periodontal disease groups, indicating that the detection frequency and levels of recovery of some periodontal pathogens are different in teeth affected by different forms of periodontal disease.

Rapid diagnostic testing for community-acquired pneumonia: can innovative technology for clinical microbiology be exploited?

Science.gov (United States)

Yu, Victor L; Stout, Janet E

2009-12-01

Two nonsynchronous events have affected the management of community-acquired pneumonia (CAP): spiraling empiricism for CAP and the "golden era" of clinical microbiology. The development of broad-spectrum antibiotics has led to widespread empiric use without ascertaining the etiology of the infecting microbe. Unfortunately, this approach clashes with the second event, which is the advent of molecular-based microbiology that can identify the causative pathogen rapidly at the point of care. The urinary antigen is a most effective rapid test that has allowed targeted therapy for Legionnaire disease at the point of care. The high specificity (> 90%) allows the clinician to administer appropriate anti-Legionella therapy based on a single rapid test; however, its low sensitivity (76%) means that a notable number of cases of Legionnaire disease will go undiagnosed if other tests, especially culture, are not performed. Further, culture for Legionella is not readily available. If a culture is not performed, epidemiologic identification of the source of the bacterium cannot be ascertained by molecular fingerprinting of the patient and the putative source strain. We recommend resurrection of the basic principles of infectious disease, which are to identify the microbial etiology of the infection and to use narrow, targeted antimicrobial therapy. To reduce antimicrobial overuse with subsequent antimicrobial resistance, these basic principles must be applied in concert with traditional and newer tests in the clinical microbiology laboratory.

Progress in the clinical development and utilization of vision prostheses: an update

Directory of Open Access Journals (Sweden)

Brandli A

2016-05-01

Full Text Available Alice Brandli, Chi D Luu, Robyn H Guymer, Lauren N Ayton Centre for Eye Research Australia, Department of Surgery (Ophthalmology, The University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia Abstract: Vision prostheses, or “bionic eyes”, are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field. Keywords: vision prostheses, bionic eye, vision restoration, blindness, medical bionics, retinitis pigmentosa

Completed suicide in a case of clinically diagnosed progressive supranuclear palsy.

Science.gov (United States)

Wiener, Jennifer; Moran, Maria T; Haut, Marc W

2015-08-01

We present the clinical history and the cognitive and behavioral presentations of a male patient with suspected progressive supranuclear palsy (PSP) who fatally shot himself in the head. We believe his act of suicide was the consequence of impulsivity, rather than primary depression or mood disturbance. In cases of suspected PSP and other atypical parkinsonisms, health professionals must be aware of neurobehavioral risk factors for suicide attempts and completions to promote patient safety; however, the literature on this topic is sparse. Our case highlights the potentially lethal consequences of impulsivity and other neuropsychiatric symptoms in PSP and related syndromes.

Surgical assessment clinic - One stop emergency out-patient clinic for rapid assessment, reduced admissions and improved acute surgical service: A quality improvement study

Directory of Open Access Journals (Sweden)

Christina A.W. Macano

2017-11-01

Conclusion: By providing suitable guidance for referring practitioners we have optimised our clinic use significantly and improved our acute ambulatory surgical care. We have reduced admissions, provided rapid treatment and have established a service that helps address the ever increasing demand on acute services within the NHS.

Clinical implications from daily physiotherapy examination of 131 acute hamstring injuries and their association with running speed and rehabilitation progression.

Science.gov (United States)

Whiteley, Rod; van Dyk, Nicol; Wangensteen, Arnlaug; Hansen, Clint

2018-03-01

To investigate the association of daily clinical measures and the progression of rehabilitation and perceived running effort. A cohort of 131 athletes with an MRI-confirmed acute hamstring injury underwent a standardised criteria-based rehabilitation protocol. Descriptive and inferential statistics were used to investigate the association between daily clinical subjective and objective measures and both the progression of rehabilitation and perceived running effort. These measures included different strength, palpation, flexibility and functional tests. Inter-rater and intrarater reliability and minimal detectable change were established for the clinical measures of strength and flexibility by examining measures taken on consecutive days for the uninjured leg. The progression of the daily measures was seen to be non-linear and varied according to the measure. Intra-rater reliability for the strength and flexibility measures were excellent (95% CI ≥0.85 for all measures). Strength (in the outer range position) and flexibility (in maximum hip flexion with active knee extension (MHFAKE) in supine) were best associated with rehabilitation progression and perceived running effort. Additionally, length of pain on palpation was usefully associated with rehabilitation progression. At lower perceived running effort there was a large variation in actual running speed. Daily physical measures of palpation pain, outer range strength, MHFAKE and reported pain during daily activity are useful to inform the progression of rehabilitation. NCT01812564 and NCT02104258. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prehospital care training in a rapidly developing economy: a multi-institutional study.

Science.gov (United States)

Vyas, Dinesh; Hollis, Michael; Abraham, Rohit; Rustagi, Neeti; Chandra, Siddharth; Malhotra, Ajai; Rajpurohit, Vikas; Purohit, Harshada; Pal, Ranabir

2016-06-01

The trauma pandemic is one of the leading causes of death worldwide but especially in rapidly developing economies. Perhaps, a common cause of trauma-related mortality in these settings comes from the rapid expansion of motor vehicle ownership without the corresponding expansion of national prehospital training in developed countries. The resulting road traffic injuries often never make it to the hospital in time for effective treatment, resulting in preventable disability and death. The current article examines the development of a medical first responder training program that has the potential to reduce this unnecessary morbidity and mortality. An intensive training workshop has been differentiated into two progressive tiers: acute trauma training (ATT) and broad trauma training (BTT) protocols. These four-hour and two-day protocols, respectively, allow for the mass education of laypersons-such as police officials, fire brigade, and taxi and/or ambulance drivers-who are most likely to interact first with prehospital victims. Over 750 ATT participants and 168 BTT participants were trained across three Indian educational institutions at Jodhpur and Jaipur. Trainees were given didactic and hands-on education in a series of critical trauma topics, in addition to pretraining and post-training self-assessments to rate clinical confidence across curricular topics. Two-sample t-test statistical analyses were performed to compare pretraining and post-training confidence levels. Program development resulted in recruitment of a variety of career backgrounds for enrollment in both our ATT and BTT workshops. The workshops were run by local physicians from a wide spectrum of medical specialties and previously ATT-trained police officials. Statistically significant improvements in clinical confidence across all curricular topics for ATT and BTT protocols were identified (P developing settings. Program expansion can offer an exponential growth in the training rate of medical

RESULTS OF AN OPEN CLINICAL STUDY OF THE EFFICACY OF LEFLUNOMIDE IN RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

I M Marusenko

2009-06-01

Conclusion. The new basic drug leflunomide is as effective as the gold standard methotrexate, at the same time it allows clinical improvement to be more rapidly achieved. Leflunomide also slows down the rate of progression of erosive arthritis and it is well tolerated.

Radiological and clinical course of pneumonia in patients with avian influenza H5N1

International Nuclear Information System (INIS)

Bay, Ali; Etlik, Omer; Oner, A. Faik; Unal, Ozkan; Arslan, Halil; Bora, Aydin; Davran, Ramazan; Yuca, Sevil Ari; Dogan, Murat

2007-01-01

Introduction: We evaluated chest X-ray and clinical findings of patients with lower respiratory tract infection due to influenza H5N1 and presented the radiological findings and clinical course of the infection. Materials and methods: Between December 2005 and February 2006, eight hospitalized patients (median age 10, 5-15 years) with avian-flu were evaluated in this study. All patients were evaluated with chest X-ray and four of them with CT scan. Post mortem pathological characterization were also available for three of the patients. Results: A rapidly progressive pneumonia with high mortality rate was observed especially for cases with late admission. The major radiologic abnormalities were extensive pneumonic infiltration with segmental and multifocal distribution, mostly located in lower zones of the lung. No pleural effusion and hilar lymphadenopathy was noted. Conclusion: Avian flu may be presented as rapidly progressive pneumonia. The chest radiography has an important role in diagnosis and should be obtained daily because of rapid change of the findings that may necessitate prompt action

Radiological and clinical course of pneumonia in patients with avian influenza H5N1

Energy Technology Data Exchange (ETDEWEB)

Bay, Ali [Yuzuncu Yil University, Faculty of Medicine, Department of Pediatrics, Van (Turkey)]. E-mail: bayalibay@yahoo.com; Etlik, Omer [Yuzuncu Yil University, Faculty of Medicine, Department of Radiology, Van (Turkey); Oner, A. Faik [Yuzuncu Yil University, Faculty of Medicine, Department of Pediatrics, Van (Turkey); Unal, Ozkan [Yuzuncu Yil University, Faculty of Medicine, Department of Radiology, Van (Turkey); Arslan, Halil [Yuzuncu Yil University, Faculty of Medicine, Department of Radiology, Van (Turkey); Bora, Aydin [Yuzuncu Yil University, Faculty of Medicine, Department of Radiology, Van (Turkey); Davran, Ramazan [Yuzuncu Yil University, Faculty of Medicine, Department of Radiology, Van (Turkey); Yuca, Sevil Ari [Yuzuncu Yil University, Faculty of Medicine, Department of Pediatrics, Van (Turkey); Dogan, Murat [Yuzuncu Yil University, Faculty of Medicine, Department of Pediatrics, Van (Turkey)

2007-02-15

Introduction: We evaluated chest X-ray and clinical findings of patients with lower respiratory tract infection due to influenza H5N1 and presented the radiological findings and clinical course of the infection. Materials and methods: Between December 2005 and February 2006, eight hospitalized patients (median age 10, 5-15 years) with avian-flu were evaluated in this study. All patients were evaluated with chest X-ray and four of them with CT scan. Post mortem pathological characterization were also available for three of the patients. Results: A rapidly progressive pneumonia with high mortality rate was observed especially for cases with late admission. The major radiologic abnormalities were extensive pneumonic infiltration with segmental and multifocal distribution, mostly located in lower zones of the lung. No pleural effusion and hilar lymphadenopathy was noted. Conclusion: Avian flu may be presented as rapidly progressive pneumonia. The chest radiography has an important role in diagnosis and should be obtained daily because of rapid change of the findings that may necessitate prompt action.

Progress of assessment and rehabilitation therapy of cognitive impairment

Directory of Open Access Journals (Sweden)

Yuan-yuan TAO

2017-07-01

Full Text Available  Cognitive impairment is one of major disorders after brain injury. With the rapid development of rehabilitation medicine in China, more and more attention was focused on it. The methods of assessment and rehabilitation therapy of cognitive impairment are more widely used in clinic. Based on traditional methods of assessment and rehabilitation therapy, driven by the development of computer, Internet and Internet of Things, more and more new methods emerged. This article intends to review the commonly used assessment and rehabilitation therapy of cognitive impairment and their progress. DOI: 10.3969/j.issn.1672-6731.2017.05.002

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

Science.gov (United States)

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEFfunction was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEFfunction decline and progression to the renal end point.

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

Science.gov (United States)

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Implementing RapidArc into clinical routine

DEFF Research Database (Denmark)

Van Esch, Ann; Huyskens, Dominique P; Behrens, Claus F

2011-01-01

With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto...

Economic impact of rapid diagnostic methods in Clinical Microbiology: Price of the test or overall clinical impact.

Science.gov (United States)

Cantón, Rafael; Gómez G de la Pedrosa, Elia

2017-12-01

The need to reduce the time it takes to establish a microbiological diagnosis and the emergence of new molecular microbiology and proteomic technologies has fuelled the development of rapid and point-of-care techniques, as well as the so-called point-of-care laboratories. These laboratories are responsible for conducting both techniques partially to response to the outsourcing of the conventional hospital laboratories. Their introduction has not always been accompanied with economic studies that address their cost-effectiveness, cost-benefit and cost-utility, but rather tend to be limited to the unit price of the test. The latter, influenced by the purchase procedure, does not usually have a regulated reference value in the same way that medicines do. The cost-effectiveness studies that have recently been conducted on mass spectrometry in the diagnosis of bacteraemia and the use of antimicrobials have had the greatest clinical impact and may act as a model for future economic studies on rapid and point-of-care tests. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

DEFF Research Database (Denmark)

Fontdevila, Maria Casadellà; Cozzi-Lepri, Alessandro; Phillips, Andrew

2014-01-01

INTRODUCTION: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA...

HPLC method for rapidly following biodiesel fuel transesterification reaction progress using a core-shell column.

Science.gov (United States)

Allen, Samuel J; Ott, Lisa S

2012-07-01

There are a wide and growing variety of feedstocks for biodiesel fuel. Most commonly, these feedstocks contain triglycerides which are transesterified into the fatty acid alkyl esters (FAAEs) which comprise biodiesel fuel. While the tranesterification reaction itself is simple, monitoring the reaction progress and reaction products is not. Gas chromatography-mass spectrometry is useful for assessing the FAAE products, but does not directly address either the tri-, di-, or monoglycerides present from incomplete transesterification or the free fatty acids which may also be present. Analysis of the biodiesel reaction mixture is complicated by the solubility and physical property differences among the components of the tranesterification reaction mixture. In this contribution, we present a simple, rapid HPLC method which allows for monitoring all of the main components in a biodiesel fuel transesterification reaction, with specific emphasis on the ability to monitor the reaction as a function of time. The utilization of a relatively new, core-shell stationary phase for the HPLC column allows for efficient separation of peaks with short elution times, saving both time and solvent.

Canavan disease - unusual imaging features in a child with mild clinical presentation

International Nuclear Information System (INIS)

Nguyen, Ho V.; Ishak, Gisele E.

2015-01-01

Canavan disease is a rare hereditary leukodystrophy that manifests in early childhood. Associated with rapidly progressive clinical deterioration, it usually results in death by the third year of life. The predominant MRI appearance is diffuse and symmetrical white matter disease. We discuss an atypical, late presentation of Canavan disease with a benign clinical course and uncharacteristic imaging features. This case introduces a previously unreported pattern of diffuse cortical abnormality without significant white matter involvement. (orig.)

Canavan disease - unusual imaging features in a child with mild clinical presentation

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Ho V.; Ishak, Gisele E. [University of Washington, Department of Radiology, Seattle Children' s Hospital, Seattle, WA (United States)

2015-03-01

Canavan disease is a rare hereditary leukodystrophy that manifests in early childhood. Associated with rapidly progressive clinical deterioration, it usually results in death by the third year of life. The predominant MRI appearance is diffuse and symmetrical white matter disease. We discuss an atypical, late presentation of Canavan disease with a benign clinical course and uncharacteristic imaging features. This case introduces a previously unreported pattern of diffuse cortical abnormality without significant white matter involvement. (orig.)

Identification of clinical target areas in the brainstem of prion‐infected mice

Science.gov (United States)

Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

2015-01-01

Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

Science.gov (United States)

Denne, J S; Stone, A M; Bailey-Iacona, R; Chen, T-T

2013-01-01

Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

Progressive cerebral atrophy in neuromyelitis optica.

Science.gov (United States)

Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

2015-12-01

We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

Research progress of motor function assessments and their clinical applications in Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

Wei SHI

2015-07-01

Full Text Available Duchenne muscular dystrophy (DMD, clinically featured as progressive skeletal muscle atrophy with gradual loss of muscle strength and activity abilities, is the most common genetic muscular disease in children throughout the world. The core and continuous characteristic of DMD is motor dysfunction. Motor function assessments of DMD are now focusing on muscle strength, walking ability, range of motion and ability of activities, still without unified standards. Confirming the comprehensive, scientific, reasonable and accurate evaluation tools for DMD assessment is the premise of research in motor developmental rules of DMD, which will help to better understand the motor progress of DMD and to supply evidences for choosing treatment methods, confirming timing of intervention, assessing effect of treatments and designing rehabilitation plans. DOI: 10.3969/j.issn.1672-6731.2015.06.002

Combining Electrochemical Sensors with Miniaturized Sample Preparation for Rapid Detection in Clinical Samples

Science.gov (United States)

Bunyakul, Natinan; Baeumner, Antje J.

2015-01-01

Clinical analyses benefit world-wide from rapid and reliable diagnostics tests. New tests are sought with greatest demand not only for new analytes, but also to reduce costs, complexity and lengthy analysis times of current techniques. Among the myriad of possibilities available today to develop new test systems, amperometric biosensors are prominent players—best represented by the ubiquitous amperometric-based glucose sensors. Electrochemical approaches in general require little and often enough only simple hardware components, are rugged and yet provide low limits of detection. They thus offer many of the desirable attributes for point-of-care/point-of-need tests. This review focuses on investigating the important integration of sample preparation with (primarily electrochemical) biosensors. Sample clean up requirements, miniaturized sample preparation strategies, and their potential integration with sensors will be discussed, focusing on clinical sample analyses. PMID:25558994

Rapid detection of methicillin-resistant Staphylococcus aureus directly from clinical samples: methods, effectiveness and cost considerations

Directory of Open Access Journals (Sweden)

Stürenburg, Enno

2009-07-01

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA isolates is a serious public health problem whose ever-increasing rate is commensurate with the pressure it is exerting on the healthcare system. At present, more than 20% of clinical S. aureus isolates in German hospitals are methicillin resistant. Strategies from low-prevalence countries show that this development is not necessarily inevitable. In the Scandinavian countries and the Netherlands, thanks to a rigorous prevention programme, MRSA prevalence has been kept at an acceptably low level (<1–3%. Central to these ‘search and destroy’ control strategies is an admission screening using several MRSA swabs taken from mucocutaneous colonisation sites of high-risk patients (‘MRSA surveillance’. It has also been reported that the speed with which MRSA carriage is detected has an important role to play, as it is a key component of any effective strategy to prevent the pathogen from spreading. Since MRSA culturing involves a 2–3 day delay before the final results are available, rapid detection techniques (commonly referred to as ‘MRSA rapid tests’ using PCR methods and, most recently, rapid culturing methods have been developed. The implementation of rapid tests reduces the time of detection of MRSA carriers from 48–72 to 2–5 h. Clinical evaluation data have shown that MRSA can thus be detected with very high sensitivity. Specificity however is sometimes impaired due to false-positive PCR signals occurring in mixed flora specimens. In order to rule out any false-positive PCR results, a culture screen must always be carried out simultaneously.The data provide preliminary evidence that a PCR assay can reduce nosocomial MRSA transmission in high-risk patients or high-risk areas, whereas an approach that screens all patients admitted to the hospital is probably not effective. Information concerning the cost-effectiveness of rapid MRSA tests is still sparse and thus the issue remains

Laser-induced breakdown spectroscopy (LIBS): an overview of recent progress and future potential for biomedical applications.

Science.gov (United States)

Rehse, S J; Salimnia, H; Miziolek, A W

2012-02-01

The recent progress made in developing laser-induced breakdown spectroscopy (LIBS) has transformed LIBS from an elemental analysis technique to one that can be applied for the reagentless analysis of molecularly complex biological materials or clinical specimens. Rapid advances in the LIBS technology have spawned a growing number of recently published articles in peer-reviewed journals which have consistently demonstrated the capability of LIBS to rapidly detect, biochemically characterize and analyse, and/or accurately identify various biological, biomedical or clinical samples. These analyses are inherently real-time, require no sample preparation, and offer high sensitivity and specificity. This overview of the biomedical applications of LIBS is meant to summarize the research that has been performed to date, as well as to suggest to health care providers several possible specific future applications which, if successfully implemented, would be significantly beneficial to humankind.

Clinical Investigation Program Annual Progress Report

Science.gov (United States)

1989-10-01

Meeting, Washington DC, September 1989 Parsons MK: Acute Shift of Right Ventricular Distensibility After Balloon Pulmonary Vavuloplasty. American Heart...selected range of motion using both concentric and eccentric muscular contractions. PROGRESS: No. of Subjects Enrolled - To Date: 8 Reporting Period: 8 1

A clinical measure of maximal and rapid stepping in older women.

Science.gov (United States)

Medell, J L; Alexander, N B

2000-08-01

In older adults, clinical measures have been used to assess fall risk based on the ability to maintain stance or to complete a functional task. However, in an impending fall situation, a stepping response is often used when strategies to maintain stance are inadequate. We examined how maximal and rapid stepping performance might differ among healthy young, healthy older, and balance-impaired older adults, and how this stepping performance related to other measures of balance and fall risk. Young (Y; n = 12; mean age, 21 years), unimpaired older (UO; n = 12; mean age, 69 years), and balance-impaired older women IO; n = 10; mean age, 77 years) were tested in their ability to take a maximal step (Maximum Step Length or MSL) and in their ability to take rapid steps in three directions (front, side, and back), termed the Rapid Step Test (RST). Time to complete the RST and stepping errors occurring during the RST were noted. The IO group, compared with the Y and UO groups, demonstrated significantly poorer balance and higher fall risk, based on performance on tasks such as unipedal stance. Mean MSL was significantly higher (by 16%) in the Y than in the UO group and in the UO (by 30%) than in the IO group. Mean RST time was significantly faster in the Y group versus the UO group (by 24%) and in the UO group versus the IO group (by 15%). Mean RST errors tended to be higher in the UO than in the Y group, but were significantly higher only in the UO versus the IO group. Both MSL and RST time correlated strongly (0.5 to 0.8) with other measures of balance and fall risk including unipedal stance, tandem walk, leg strength, and the Activities-Specific Balance Confidence (ABC) scale. We found substantial declines in the ability of both unimpaired and balance-impaired older adults to step maximally and to step rapidly. Stepping performance is closely related to other measures of balance and fall risk and might be considered in future studies as a predictor of falls and fall

An investigation on clinical, radiological and biochemical methods for assessing periodontitis activity

International Nuclear Information System (INIS)

Janssen, P.T.M.

1987-01-01

In order to recognize in which stage rapidly progressing destruction of periodontal ligament fibers occurs, a number of diagnostic methods are studied in this thesis. It turns out that the actual much utilized clinical methods can not be improved while radiological and biochemical diagnositic methods are much more promising. 106 refs.; 20 figs.; 36 tabs

Clinical utility of MR imaging in chronic progressive radiation myelopathy

International Nuclear Information System (INIS)

Melki, P.S.; Halimi, P.; Wibault, P.; Doyon, D.

1990-01-01

This paper defines the diagnostic and prognostic value of MR imaging in chronic progressive radiation myelopathy 9CPRM). In this series, MR imaging showed excellent sensitivity (199%) for the demonstration of radiation-induced lesions of the spinal cord. Fifty percent of the cases showed spinal cord hypertrophy (pseudotumoral, 33%; cystic, 17%) occurring within 8 months of the clinical onset of myelopathy. The remaining 50% showed spinal cord atrophy, which occurred more than 8 months following the onset of myelopathy. These medullary lesions were located at least partially in the radiation field but extended beyond its boundaries in 73% of the cases. MR imaging helped to establish disease prognosis: spinal cord hypertrophy was usually associated with neurologic deterioration and fatal outcome within a mean of 11.5 months; in spinal atrophy, neurologic deficit was often static and survival rates were better

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

Science.gov (United States)

Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

2017-09-01

Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

2011-01-01

Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

Effect of intensive plasma exchange (PE) in rapidly progressive crescentic glomerulonephritis (RPCGN).

Science.gov (United States)

D'Amico, G; Sinico, R; Fornasieri, A; Ferrario, F; Colasanti, G; Porri, M T; Paracchini, M L; Gibelli, A

1983-07-01

Ten adult patients with RPCGN (crescents in greater than 70% of glomeruli), primary in 6 and associated with systemic diseases in 4, were treated with PE, associated with oral steroids (P) and cyclophosphamide (C) in all cases and with intravenous methylprednisolone pulses (MP) in 7 cases. Four out of ten patients were anuric and needed dialysis treatment at the start of treatment. Therapeutic benefit, i.e. reversal of the trend to further deterioration and substantial improvement of GFR, was achieved in 8 out of 10 patients (80%), including 2 of 4 anuric patients, and in 7 of those (8) who had still active cellular crescents (87.5%). Similar therapeutic benefit had been achieved only in 10% of a comparable population of 10 patients with RPCGN treated before 1980 with P and C, without PE or MP pulses. It is difficult to establish whether the better therapeutic results in the more recently treated group were due to PE or to MP pulses of to both the new approaches, even though the clinical improvement obtained in all the 3 patients treated with PE without concomitant MP suggest a specific beneficial role for PE. RPCGN is a catastrophic illness characterized by progressive deterioration of kidney function, resulting in oliguria and uremia, usually within weeks or months. The most consistent histopathologic finding is the presence of extensive glomerular crescents resulting from proliferation of the extracapillary epithelial cell lining of Bowman's capsule. It is apparent that RPCGN is not a homogeneous entity, clinically, histologically or immunohistologically, but rather a clinicopathologic syndrome, the features of which may be seen in a variety of systemic disorders, including SLE, polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, cryoglobulinemia, and subacute bacterial endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of primary progressive multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Kingwell, Elaine; Rieckmann, Peter; Tremlett, Helen

2009-01-01

Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few

Progressive technologies in furniture design

OpenAIRE

Šebková, Martina

2014-01-01

Šebková, M. Progressive technologies in furniture design. Diploma thesis, Brno, Mendel University in Brno, 2014 Diploma thesis 'Progressive technologies in furniture design' is focused on the use of modern technologies in furniture production. The theoretical part explains the basic terms, technology and material options. It focuses mainly on the production of 3D printed furniture and possibilities of virtual testing, measurements, scanning and rapid prototyping. Practical part of diploma the...

Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima‐Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study

Science.gov (United States)

Desvarieux, Moïse; Demmer, Ryan T.; Jacobs, David R.; Papapanou, Panos N.; Sacco, Ralph L.; Rundek, Tatjana

2013-01-01

Background No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis. Methods and Results The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trendperiodontal microbial status (Δetiologic dominance). Conclusion Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

Science.gov (United States)

Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

2016-01-01

Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification.

Directory of Open Access Journals (Sweden)

Igor O Korolev

Full Text Available Individuals with mild cognitive impairment (MCI have a substantially increased risk of developing dementia due to Alzheimer's disease (AD. In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level.Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139 and those who did not (n = 120 during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework.Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87. Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex. Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions.We developed an accurate prognostic model for predicting MCI-to-dementia progression

Risk of progression from mild memory impairment to clinically diagnosable Alzheimer's disease in a Japanese community (from the Nakayama Study).

Science.gov (United States)

Sonobe, Naomi; Hata, Ryuji; Ishikawa, Tomohisa; Sonobe, Kantaro; Matsumoto, Teruhisa; Toyota, Yasutaka; Mori, Takaaki; Fukuhara, Ryuji; Komori, Kenjiro; Ueno, Shu-Ichi; Tanimukai, Satoshi; Ikeda, Manabu

2011-06-01

Memory impairment has been proposed as the most common early sign of Alzheimer's disease (AD). The aims of this work were to evaluate the risk of progression from mild memory impairment/no dementia (MMI/ND) to clinically diagnosable AD in a community-based prospective cohort and to establish the risk factors for progression from MMI/ND to AD in the elderly. Elderly subjects aged over 65 years were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit on objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. A total of 104 MMI/ND subjects selected from 1242 community-dwellers were followed longitudinally for five years. During the five-year follow-up, 11 (10.6%) subjects were diagnosed with AD, five (4.8%) with vascular dementia (VaD), and six (5.8%) with dementia of other etiology. Logistic regression analysis revealed that diabetes mellitus (DM) and a family history of dementia (within third-degree relatives) were positively associated with progression to AD, while no factor was significantly associated with progression to VaD or all types of dementia. DM and a family history of dementia were significant risk factors for progression from MMI/ND to clinically diagnosable AD in the elderly in a Japanese community.

Clinical Evaluation of Rapid Diagnostic Test Kit for Scrub Typhus with Improved Performance.

Science.gov (United States)

Kim, Young-Jin; Park, Sungman; Premaratna, Ranjan; Selvaraj, Stephen; Park, Sang-Jin; Kim, Sora; Kim, Donghwan; Kim, Min Soo; Shin, Dong Hoon; Choi, Kyung-Chan; Kwon, Soon-Hwan; Seo, Wonjun; Lee, Nam Taek; Kim, Seung-Han; Kang, Heui Keun; Kim, Yoon-Won

2016-08-01

Diagnosis of scrub typhus is challenging due to its more than twenty serotypes and the similar clinical symptoms with other acute febrile illnesses including leptospirosis, murine typhus and hemorrhagic fever with renal syndrome. Accuracy and rapidity of a diagnostic test to Orientia tsutsugamushi is an important step to diagnose this disease. To discriminate scrub typhus from other diseases, the improved ImmuneMed Scrub Typhus Rapid Diagnostic Test (RDT) was evaluated in Korea and Sri Lanka. The sensitivity at the base of each IgM and IgG indirect immunofluorescent assay (IFA) in Korean patients was 98.6% and 97.1%, and the specificity was 98.2% and 97.7% respectively. The sensitivity and specificity for retrospective diagnosis at the base of IFA in Sri Lanka was 92.1% and 96.1%. ImmuneMed RDT was not reactive to any serum from seventeen diseases including hemorrhagic fever with renal syndrome (n = 48), leptospirosis (n = 23), and murine typhus (n = 48). ImmuneMed RDT shows superior sensitivity (98.6% and 97.1%) compared with SD Bioline RDT (84.4% at IgM and 83.3% at IgG) in Korea. The retrospective diagnosis of ImmuneMed RDT exhibits 94.0% identity with enzyme-linked Immunosorbent assay (ELISA) using South India patient serum samples. These results suggest that this RDT can replace other diagnostic tests and is applicable for global diagnosis of scrub typhus. This rapid and accurate diagnosis will be beneficial for diagnosing and managing scrub typhus.

Surgical treatment of progressive ethmoidal hematoma aided by computed tomography in a foal

International Nuclear Information System (INIS)

Colbourne, C.M.; Rosenstein, D.S.; Steficek, B.A.; Yovich, J.V.; Stick, J.A.

1997-01-01

A progressive ethmoidal hematoma (PEH) was treated successfully in a 4-week-old Belgian filly by surgical removal, using a frontonasal bone flap. The filly had respiratory stridor, epistaxis, and facial enlargement over the left paranasal sinuses, which had progressively increased in size since birth. Computed tomographic images of the head obtained with the foal under general anesthesia were useful in determining the extent and nature of the soft-tissue mass and planning surgical intervention. On the basis of the histologic appearance of the mass, a diagnosis of PEH was made. Twelve months after surgery, the facial appearance was normal and the abnormal appearance of the ethmoid region on endoscopic evaluation was less obvious, with return of the nasal septum to a normal position. Progressive ethmoidal hematoma is uncommon and, to our knowledge, has not been reported in a neonate. Clinical signs of PEH in this foal were atypical because of the rapid enlargement of the mass, extent of facial deformity, and minimal epistaxis and interoperative hemorrhage

Clinical evaluation of a novel population-based regression analysis for detecting glaucomatous visual field progression.

Science.gov (United States)

Kovalska, M P; Bürki, E; Schoetzau, A; Orguel, S F; Orguel, S; Grieshaber, M C

2011-04-01

The distinction of real progression from test variability in visual field (VF) series may be based on clinical judgment, on trend analysis based on follow-up of test parameters over time, or on identification of a significant change related to the mean of baseline exams (event analysis). The aim of this study was to compare a new population-based method (Octopus field analysis, OFA) with classic regression analyses and clinical judgment for detecting glaucomatous VF changes. 240 VF series of 240 patients with at least 9 consecutive examinations available were included into this study. They were independently classified by two experienced investigators. The results of such a classification served as a reference for comparison for the following statistical tests: (a) t-test global, (b) r-test global, (c) regression analysis of 10 VF clusters and (d) point-wise linear regression analysis. 32.5 % of the VF series were classified as progressive by the investigators. The sensitivity and specificity were 89.7 % and 92.0 % for r-test, and 73.1 % and 93.8 % for the t-test, respectively. In the point-wise linear regression analysis, the specificity was comparable (89.5 % versus 92 %), but the sensitivity was clearly lower than in the r-test (22.4 % versus 89.7 %) at a significance level of p = 0.01. A regression analysis for the 10 VF clusters showed a markedly higher sensitivity for the r-test (37.7 %) than the t-test (14.1 %) at a similar specificity (88.3 % versus 93.8 %) for a significant trend (p = 0.005). In regard to the cluster distribution, the paracentral clusters and the superior nasal hemifield progressed most frequently. The population-based regression analysis seems to be superior to the trend analysis in detecting VF progression in glaucoma, and may eliminate the drawbacks of the event analysis. Further, it may assist the clinician in the evaluation of VF series and may allow better visualization of the correlation between function and structure owing to VF

Patellofemoral Osteoarthritis Progression and Alignment Changes after Open-Wedge High Tibial Osteotomy Do Not Affect Clinical Outcomes at Mid-term Follow-up.

Science.gov (United States)

Goshima, Kenichi; Sawaguchi, Takeshi; Shigemoto, Kenji; Iwai, Shintaro; Nakanishi, Akira; Ueoka, Ken

2017-10-01

To evaluate the clinical and radiological outcomes of open-wedge high tibial osteotomy (OWHTO) with respect to the patellofemoral joint and to assess whether patellofemoral osteoarthritis (OA) progression and alignment changes after OWHTO affect clinical outcomes. Inclusion criteria were consecutive patients who underwent OWHTO from March 2005 to September 2013. Exclusion criteria were loss to follow-up within 2 years and absence of second-look arthroscopy findings at the time of plate removal. The clinical parameters, including anterior knee pain while climbing stairs, Japanese Orthopedic Association score, and Oxford Knee Score, were evaluated. Radiological outcomes, including weight-bearing line ratio, modified Blackburne-Peel ratio, posterior tibial slope, tilting angle, lateral shift ratio, and patellofemoral OA (Kellgren-Lawrence grade), were evaluated preoperatively and at the final follow-up. Cartilage status (International Cartilage Repair Society grade) was evaluated at the initial HTO and at plate removal. Fifty-three patients (60 knees) were included in this study. The mean follow-up was 58.2 ± 22.4 months. Two knees (3%) presented with mild anterior knee pain after OWHTO. The mean Japanese Orthopedic Association score (66.9 ± 11.2 to 91.2 ± 9.7) significantly improved (P patellofemoral OA had progressed in 15 knees (27%), and arthroscopically patellofemoral cartilage degeneration had progressed in 27 knees (45%). However, there was no significant correlation between changes in patellofemoral alignment and clinical outcomes. Changes in patellofemoral alignment and patellofemoral OA progression did not affect the clinical outcomes of OWHTO at mid-term follow-up. Level IV, therapeutic case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).

Science.gov (United States)

Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda; Lodahl, Marianne; Tranebjærg, Lisbeth; Cesur, Yasar; Dogan, Murat; Yilmaz, Cahide; Akgun, Cihangir; Acikgoz, Mehmet

2012-01-01

Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

Science.gov (United States)

Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Progression of Dysphagia in Spinocerebellar Ataxia Type 6.

Science.gov (United States)

Isono, Chiharu; Hirano, Makito; Sakamoto, Hikaru; Ueno, Shuichi; Kusunoki, Susumu; Nakamura, Yusaku

2017-06-01

Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant triplet repeat disease, predominantly affects the cerebellum with a late onset and generally good prognosis. Dysphagia is commonly associated with the outcomes of neurodegenerative diseases such as SCA6. Although the characteristics of dysphagia have been rarely reported in SCA6, our previous study indicated that dysphagia is generally milder in SCA6 than in SCA3, another inherited ataxia with multisystem involvement. However, abnormalities in the pharyngeal phase in SCA6 were indistinguishable from those in SCA3, with no explainable reason. To determine the reason, we repeatedly performed videofluoroscopic examinations (VF) in 14 patients with SCA6. The results showed that the gross progression of dysphagia was apparently slow, but four patients had progressive dysphagia at an early disease stage; dysphagia began within 10 years from the onset of ataxia and rapidly progressed. A common clinical feature of the four patients was a significantly older age at the onset of ataxia (74.0 vs. 60.3 years), associated with significantly shorter triplet repeats. This finding surprisingly indicated that patients who had shorter repeats and thereby later onset and potentially better prognoses were at risk for dysphagia-associated problems. Ischemic changes, homozygous mutation, and diabetes mellitus as well as aging might have contributed to the observed progressive dysphagia. We found that conventionally monitored somatosensory evoked potentials at least partly reflected progressive dysphagia. Despite the small study group, our findings suggest that clinicians should carefully monitor dysphagia in patients with SCA6 who are older at disease onset (>60 years).

Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

Science.gov (United States)

McKenna, Dillon; Peever, John

2017-05-01

During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and

Rheumatoid disease without arthritis; clinical case of pulmonary fibrosis, rheumatoid nodulosis and positive rheumatoid factor without arthritis

International Nuclear Information System (INIS)

Ochoa Franco, Julian Andres; Canas Davila, Carlos Alberto

2003-01-01

We reported a case of a patient suffering pulmonary fibrosis rapidly progressive and a positive rheumatoid factor test with the presence of HLA DR11 y HLADR17, without arthritis, We discuss how rare is this clinical appearance, and remark the concept that rheumatoid arthritis is a systemic disease, with a wide clinical presentation, that some authors with a right criteria have called rheumatoid disease

Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

Science.gov (United States)

Pryce, Gareth; Riddall, Dieter R; Selwood, David L; Giovannoni, Gavin; Baker, David

2015-06-01

Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities that will influence relapsing autoimmunity, we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability. Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels. In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans. Although a 3 year, phase III clinical trial did not detect a beneficial effect of oral Δ9-THC in progressive MS, a planned subgroup analysis of people with less disability who progressed more rapidly, demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo. Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.

Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa

OpenAIRE

Jaya, Ziningi; Drain, Paul K.; Mashamba-Thompson, Tivani P.

2017-01-01

Introduction Rapid HIV tests have improved access to HIV diagnosis and treatment by providing quick and convenient testing in rural clinics and resource-limited settings. In this study, we evaluated the quality management system for voluntary and provider-initiated point-of-care HIV testing in primary healthcare (PHC) clinics in rural KwaZulu-Natal (KZN), South Africa. Material and methods We conducted a quality assessment audit in eleven PHC clinics that offer voluntary HIV testing and couns...

Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment.

Science.gov (United States)

Abou-El-Enein, Mohamed; Cathomen, Toni; Ivics, Zoltán; June, Carl H; Renner, Matthias; Schneider, Christian K; Bauer, Gerhard

2017-10-05

As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues. Copyright © 2017 Elsevier Inc. All rights reserved.

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

Science.gov (United States)

Gomez-Ospina, Natalia; Potter, Carol J.; Xiao, Rui; Manickam, Kandamurugu; Kim, Mi-Sun; Kim, Kang Ho; Shneider, Benjamin L.; Picarsic, Jennifer L.; Jacobson, Theodora A.; Zhang, Jing; He, Weimin; Liu, Pengfei; Knisely, A. S.; Finegold, Milton J.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.; Yang, Yaping; Washington, Gabriel C.; Porteus, Matthew H.; Berquist, William E.; Kambham, Neeraja; Singh, Ravinder J.; Xia, Fan; Enns, Gregory M.; Moore, David D.

2016-01-01

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID:26888176

Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

International Nuclear Information System (INIS)

Kim, Ho Kyun; Lee, Hui Joong

2013-01-01

White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

Optimising translational oncology in clinical practice: strategies to accelerate progress in drug development.

Science.gov (United States)

Stahel, R; Bogaerts, J; Ciardiello, F; de Ruysscher, D; Dubsky, P; Ducreux, M; Finn, S; Laurent-Puig, P; Peters, S; Piccart, M; Smit, E; Sotiriou, C; Tejpar, S; Van Cutsem, E; Tabernero, J

2015-02-01

Despite intense efforts, the socioeconomic burden of cancer remains unacceptably high and treatment advances for many common cancers have been limited, suggesting a need for a new approach to drug development. One issue central to this lack of progress is the heterogeneity and genetic complexity of many tumours. This results in considerable variability in therapeutic response and requires knowledge of the molecular profile of the tumour to guide appropriate treatment selection for individual patients. While recent advances in the molecular characterisation of different cancer types have the potential to transform cancer treatment through precision medicine, such an approach presents a major economic challenge for drug development, since novel targeted agents may only be suitable for a small cohort of patients. Identifying the patients who would benefit from individual therapies and recruiting sufficient numbers of patients with particular cancer subtypes into clinical trials is challenging, and will require collaborative efforts from research groups and industry in order to accelerate progress. A number of molecular screening platforms have already been initiated across Europe, and it is hoped that these networks, along with future collaborations, will benefit not only patients but also society through cost reductions as a result of more efficient use of resources. This review discusses how current developments in translational oncology may be applied in clinical practice in the future, assesses current programmes for the molecular characterisation of cancer and describes possible collaborative approaches designed to maximise the benefits of translational science for patients with cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Economic and Clinical Impact of Sustained Use of a Progressive Mobility Program in a Neuro-ICU.

Science.gov (United States)

Hester, Jeannette M; Guin, Peggy R; Danek, Gale D; Thomas, Jaime R; Titsworth, William L; Reed, Richard K; Vasilopoulos, Terrie; Fahy, Brenda G

2017-06-01

To investigate a progressive mobility program in a neurocritical care population with the hypothesis that the benefits and outcomes of the program (e.g., decreased length of stay) would have a significant positive economic impact. Retrospective analysis of economic and clinical outcome data before, immediately following, and 2 years after implementation of the Progressive Upright Mobility Protocol Plus program (UF Health Shands Hospital, Gainesville, FL) involving a series of planned movements in a sequential manner with an additional six levels of rehabilitation in the neuro-ICU at UF Health Shands Hospital. Thirty-bed neuro-ICU in an academic medical center. Adult neurologic and neurosurgical patients: 1,118 patients in the pre period, 731 patients in the post period, and 796 patients in the sustained period. Implementation of Progressive Upright Mobility Protocol Plus. ICU length of stay decreased from 6.5 to 5.8 days in the immediate post period and 5.9 days in the sustained period (F(2,2641) = 3.1; p = 0.045). Hospital length of stay was reduced from 11.3 ± 14.1 days to 8.6 ± 8.8 post days and 8.8 ± 9.3 days sustained (F(2,2641) = 13.0; p mobility program in the neurocritical care population has clinical and financial benefits associated with its implementation and should be considered.

Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing.

Science.gov (United States)

Guerra, Sandra G; Chong, Winnie; Brown, Colin J; Navarrete, Cristina V

2018-06-05

The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high-resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high-resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9-loci (HLA-A, -B, -C, -DRB1,-DRB345 -DQB1 and -DPB1). Concordance rates of 91%-98% were obtained (for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) when compared to historical PCR-SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA-DRB1*04:07:01/04:92, HLA-DRB1*09:01:02/*09:21 and HLA-DRB1*12:01:01/*12:10). This study has demonstrated high-resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed. © 2018 John Wiley & Sons Ltd.

Progressive nature of heart failure and systems biology

Directory of Open Access Journals (Sweden)

George E. Louridas

2015-01-01

Full Text Available The progressive nature of heart failure (HF is the predominant cause for the clinical course that the HF syndrome is taking. Systems biology methodology is of the utmost importance to explain and comprehend the built-in mechanisms of adverse clinical progression. Various heart diseases produce myocardial damage with subsequent left ventricular remodeling which is the principal underlying pathophysiological mechanism for the clinical progression of HF. The self-organized positive feedback stabilization mechanisms of left ventricular remodeling, adrenergic stimulation and activation of the renin-angiotensin-aldosterone system and natriuretic peptide systems, are hierarchical adaptive processes. These adaptive processes are responsible for further left ventricular remodeling with subsequent clinical deterioration and for the emergence of clinical phenotypes. These mechanisms are counteracted with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and β-blockers in an attempt to improve the adverse clinical phenomena of HF progression in a new but clinically worse stabilization level. In this review our intention is to underline the progressive nature of the HF syndrome and to demonstrate the significance of ventricular remodeling and the role of self-organized positive feedback adaptive processes.

The Correlation between Clinical Variables and Sleep Onset Rapid Eye Movement Period Frequencies in Narcoleptic Patients

Directory of Open Access Journals (Sweden)

Jin Hwa Jeong

2010-11-01

Full Text Available Background and Objective A diagnosis of narcolepsy is defined by less than 8 minutes of mean sleep latency, and two or more sleep onset rapid eye movement periods on the Multiple Sleep Latency Test. This study examined the relationship between the sleep onset rapid eye movement period frequencies during Multiple Sleep Latency Test and narcoleptic symptom severity. Methods From March 2004 to August 2009, 126 patients suffering from excessive daytime sleepiness who visited the Sleep Disorders Clinic of St. Vincent’s Hospital at the Catholic University of Korea were tested by polysomnography and Multiple Sleep Latency Test. Subjects were divided into three groups according to the number of sleep onset rapid eye movement periods that appeared on the Multiple Sleep Latency Test. Symptom severity instruments included the Epworth Sleepiness Scale and the Stanford Center for Narcolepsy Sleep Inventory, and various sleep parameters. In addition, we performed human leukocyte antigen genotyping for human leukocyte antigen-DQB1*0602 on all patients. Results Among the three groups classified by the number of sleep onset rapid eye movement periods during Multiple Sleep Latency Test, we found no significant differences in demographic features, Epworth Sleepiness Scale, and most polysomnographic findings. However, we observed cataplexy, hypnagogic hallucination, sleep paralysis, and human leukocyte antigen-DQB1*0602 positivity more frequently in groups with higher sleep onset rapid eye movement period frequencies. In addition, the proportions of stage II sleep, REM sleep latency from polysomnography, and mean sleep latency and mean REM sleep latency from the Multiple Sleep Latency Test significantly decreased with increasing sleep onset rapid eye movement period frequency. Conclusions In this study, we demonstrated that sleep onset rapid eye movement period frequency during Multiple Sleep Latency Test correlated with sleep architecture, daytime symptom

Setting a research agenda for progressive multiple sclerosis: the International Collaborative on Progressive MS.

Science.gov (United States)

Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-11-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Science.gov (United States)

Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-01-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690

Research progress in radiolabeling imaging mechanism and clinical applications of "1"8F-FDG

International Nuclear Information System (INIS)

Zhai Shizhen; Yang Zhi; Du Jin

2011-01-01

PET/CT is one of the most advanced technologies contemporarily, achieving the combination of anatomical imaging and functional imaging. "1"8F-FDG is the most important positron radiopharmaceutical, which was used over 95% in total PET/CT imaging. FDG- PET has been extensively used in diagnosis of several kinds of diseases such as tumor, cardiac disease and epilepsy. The present review provides the history, the quality control, the imaging mechanisms as well as the research progress of the clinical applications of "1"8F-FDG. (authors)

Rapid determination of natural steroidal hormones in saliva for the clinical diagnoses

Directory of Open Access Journals (Sweden)

Oh Jin-Aa

2012-03-01

Full Text Available Abstract Background Saliva samples are easily collectable and non-invasive, and the monitoring of natural steroidal hormones, such as estrone (E1, 17β-estradiol (E2, estriol (E3, progesterone (P, and testosterone (T, in saliva has attracted much attention due to its numerous potential clinical and health-related applications. Because E1, E2, E3, P and T are useful indicators in numerous clinical and health-related diagnoses, there is a need for simultaneous determination. Results A gas chromatography-mass spectrometric assay was developed for rapid simultaneous determination of E1, E2, E3, P and T in saliva for clinical diagnoses. Extraction was achieved with a liquid extraction using 3.0 mL of pentane. The extract was dried and silylated with N-methyl-N-(trimethylsilyl trifluoroacetamide/NH4I (100:2 under a catalysis of 1.5% dithioerythritol for 10 min at 90°C. The accuracy of the analytes was in the range of 96% to 112% at concentrations of 0.05 and 0.10 μg/L (5.0 and 10.0 μg/L for E3, respectively, with relative standard deviations of less than 11%. The lowest quantification limits were from 0.002 to 0.6 μg/L for 1.0 mL of saliva. Conclusion Natural steroidal hormones were detected in the concentration ranges of nd to 0.2 μg/L in human saliva. The salivary testosterone values in the patients with prostatic carcinoma were significantly lower than in normal males. The method may useful in numerous clinical and health-related diagnoses.

Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice

DEFF Research Database (Denmark)

Ornbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille

2013-01-01

radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated.RESULTS: 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21......OBJECTIVES: To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice.METHODS: Conventional radiographs (x......-1002) and the median TNF-I period was 562 days (IQR 405-766). The median radiographic progression rate decreased from 0.7 (IQR 0-2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0-0.9) units/year in the TNF-I period (p0) in the DMARD period compared with 158 patients in the TNF-I period (p...

New imaging systems in nuclear medicine. Technical progress report, July 1, 1975--March 15, 1976

International Nuclear Information System (INIS)

Brownell, G.L.

1976-01-01

This progress report covers four areas: development of positron instrumentation, development of NUMEDICS computer system and software, application of cyclotron-produced isotopes ( 11 C, 68 Ga, 13 N, 15 O, and 82 Rb), and application of the NUMEDICS computer system in nuclear medicine. The development of transverse section positron imaging has had a significant impact and a positron camera was designed specifically for transverse section imaging of heart and lungs. The computer net (NUMEDICS II) is progressing rapidly in design and software development. Clinical studies have demonstrated the feasibility of measuring cerebral blood flow using a variety of positron emitting radiopharmaceuticals and oxygen utilization using 15 O 2 . Rubidium-82 also appears to be a promising agent for measurement of cerebral blood flow

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation

Directory of Open Access Journals (Sweden)

Benedikt Mahr

2017-12-01

-term patients and progress in pre-clinical research provide encouraging evidence that deliberately inducing tolerance through hematopoietic chimerism might eventually make it from dream to reality.

SU-E-T-23: A Developing Australian Network for Datamining and Modelling Routine Radiotherapy Clinical Data and Radiomics Information for Rapid Learning and Clinical Decision Support

Energy Technology Data Exchange (ETDEWEB)

Thwaites, D [University of Sydney, Camperdown, Sydney (Australia); Holloway, L [Ingham Institute, Sydney, NSW (Australia); Bailey, M; Carolan, M; Miller, A [Illawarra Cancer Care Centre, Wollongong, NSW (Australia); Barakat, S; Field, M [University of Sydney, Sydney, NSW (Australia); Delaney, G; Vinod, S [Liverpool Hospital, Liverpool, NSW (Australia); Dekker, A [Maastro Clinic, Maastricht (Netherlands); Lustberg, T; Soest, J van; Walsh, S [MAASTRO Clinic, Maastricht (Netherlands)

2015-06-15

Purpose: Large amounts of routine radiotherapy (RT) data are available, which can potentially add clinical evidence to support better decisions. A developing collaborative Australian network, with a leading European partner, aims to validate, implement and extend European predictive models (PMs) for Australian practice and assess their impact on future patient decisions. Wider objectives include: developing multi-institutional rapid learning, using distributed learning approaches; and assessing and incorporating radiomics information into PMs. Methods: Two initial standalone pilots were conducted; one on NSCLC, the other on larynx, patient datasets in two different centres. Open-source rapid learning systems were installed, for data extraction and mining to collect relevant clinical parameters from the centres’ databases. The European DSSs were learned (“training cohort”) and validated against local data sets (“clinical cohort”). Further NSCLC studies are underway in three more centres to pilot a wider distributed learning network. Initial radiomics work is underway. Results: For the NSCLC pilot, 159/419 patient datasets were identified meeting the PM criteria, and hence eligible for inclusion in the curative clinical cohort (for the larynx pilot, 109/125). Some missing data were imputed using Bayesian methods. For both, the European PMs successfully predicted prognosis groups, but with some differences in practice reflected. For example, the PM-predicted good prognosis NSCLC group was differentiated from a combined medium/poor prognosis group (2YOS 69% vs. 27%, p<0.001). Stage was less discriminatory in identifying prognostic groups. In the good prognosis group two-year overall survival was 65% in curatively and 18% in palliatively treated patients. Conclusion: The technical infrastructure and basic European PMs support prognosis prediction for these Australian patient groups, showing promise for supporting future personalized treatment decisions

SU-E-T-23: A Developing Australian Network for Datamining and Modelling Routine Radiotherapy Clinical Data and Radiomics Information for Rapid Learning and Clinical Decision Support

International Nuclear Information System (INIS)

Thwaites, D; Holloway, L; Bailey, M; Carolan, M; Miller, A; Barakat, S; Field, M; Delaney, G; Vinod, S; Dekker, A; Lustberg, T; Soest, J van; Walsh, S

2015-01-01

Purpose: Large amounts of routine radiotherapy (RT) data are available, which can potentially add clinical evidence to support better decisions. A developing collaborative Australian network, with a leading European partner, aims to validate, implement and extend European predictive models (PMs) for Australian practice and assess their impact on future patient decisions. Wider objectives include: developing multi-institutional rapid learning, using distributed learning approaches; and assessing and incorporating radiomics information into PMs. Methods: Two initial standalone pilots were conducted; one on NSCLC, the other on larynx, patient datasets in two different centres. Open-source rapid learning systems were installed, for data extraction and mining to collect relevant clinical parameters from the centres’ databases. The European DSSs were learned (“training cohort”) and validated against local data sets (“clinical cohort”). Further NSCLC studies are underway in three more centres to pilot a wider distributed learning network. Initial radiomics work is underway. Results: For the NSCLC pilot, 159/419 patient datasets were identified meeting the PM criteria, and hence eligible for inclusion in the curative clinical cohort (for the larynx pilot, 109/125). Some missing data were imputed using Bayesian methods. For both, the European PMs successfully predicted prognosis groups, but with some differences in practice reflected. For example, the PM-predicted good prognosis NSCLC group was differentiated from a combined medium/poor prognosis group (2YOS 69% vs. 27%, p<0.001). Stage was less discriminatory in identifying prognostic groups. In the good prognosis group two-year overall survival was 65% in curatively and 18% in palliatively treated patients. Conclusion: The technical infrastructure and basic European PMs support prognosis prediction for these Australian patient groups, showing promise for supporting future personalized treatment decisions

Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features.

Directory of Open Access Journals (Sweden)

Fumiaki Sato

2008-04-01

Full Text Available Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency.We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barrett's esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC curve: 0.8386 and 0.7910, respectively, Barrett's esophagus specimens were stratified into high-risk (HR, intermediate-risk (IR, or low-risk (LR groups. This 3-tiered stratification method retained both the high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p = 0.0022 (HR vs. IR and p<0.0001 (HR or IR vs. LR. Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy.This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.

Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

Science.gov (United States)

Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

2018-04-01

A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

Turning the tide against cancer through sustained medical innovation: the pathway to progress.

Science.gov (United States)

Abernethy, Amy; Abrahams, Edward; Barker, Anna; Buetow, Ken; Burkholder, Randy; Dalton, William S; Foti, Margaret; Frueh, Felix; Gaynor, Richard B; Kean, Marcia; Khan, Zeba; Lessor, Tracy; Lichtenfeld, J Leonard; Mendelsohn, John; van't Veer, Laura

2014-03-01

An ever-expanding understanding of the molecular basis of the more than 200 unique diseases collectively called cancer, combined with efforts to apply these insights to clinical care, is forming the foundation of an era of personalized medicine that promises to improve cancer treatment. At the same time, these extraordinary opportunities are occurring in an environment of intense pressure to contain rising healthcare costs. This environment presents a challenge to oncology research and clinical care, because both are becoming progressively more complex and expensive, and because the current tools to measure the cost and value of advances in care (e.g., comparative effectiveness research, cost-effectiveness analysis, and health technology assessments) are not optimized for an ecosystem moving toward personalized, patient-centered care. Reconciling this tension will be essential to maintaining progress in a cost-constrained environment, especially because emerging innovations in science (e.g., increasing identification of molecular biomarkers) and in clinical process (implementation of a learning healthcare system) hold potential to dramatically improve patient care, and may ultimately help address the burden of rising costs. For example, the rapid pace of innovation taking place within oncology calls for increased capability to integrate clinical research and care to enable continuous learning, so that lessons learned from each patient treated can inform clinical decision making for the next patient. Recognizing the need to define the policies required for sustained innovation in cancer research and care in an era of cost containment, the stakeholder community must engage in an ongoing dialogue and identify areas for collaboration. This article reflects and seeks to amplify the ongoing robust discussion and diverse perspectives brought to this issue by multiple stakeholders within the cancer community, and to consider how to frame the research and regulatory

Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema

DEFF Research Database (Denmark)

Vujosevic, Stela; Varano, Monica; Egan, Catherine

2015-01-01

PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were...... included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used....... A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield...

Comparison of semen parameters in samples collected by masturbation at a clinic and at home.

Science.gov (United States)

Elzanaty, Saad; Malm, Johan

2008-06-01

To investigate differences in semen quality between samples collected by masturbation at a clinic and at home. Cross-sectional study. Fertility center. Three hundred seventy-nine men assessed for infertility. None. Semen was analyzed according to World Health Organization guidelines. Seminal markers of epididymal (neutral alpha-glucosidase), prostatic (prostate-specific antigen and zinc), and seminal vesicle (fructose) function were measured. Two patient groups were defined according to sample collection location: at a clinic (n = 273) or at home (n = 106). Compared with clinic-collected semen, home-collected samples had statistically significantly higher values for sperm concentration, total sperm count, rapid progressive motility, and total count of progressive motility. Semen volume, proportion of normal sperm morphology, neutral alpha-glucosidase, prostate-specific antigen, zinc, and fructose did not differ significantly between groups. An abnormal sperm concentration (masturbation at home compared with at a clinic. This should be taken into consideration in infertility investigations.

Rapid thermal processing of semiconductors

CERN Document Server

Borisenko, Victor E

1997-01-01

Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

Remission of classic rapid cycling bipolar disorder with levothyroxine augmentation therapy in a male patient having clinical hypothyroidism

Directory of Open Access Journals (Sweden)

Chen PH

2015-02-01

Full Text Available Pao-Huan Chen, Yu-Jui Huang Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan Abstract: The literature suggests that patients with bipolar disorder, particularly females, have greater vulnerability to rapid cycling features. Levothyroxine therapy might be potentially useful to attenuate mood instability in this patient group. In contrast, reports on male patients remain limited and controversial. Herein, we report a 32-year-old male patient who had bipolar 1 disorder for 12 years who developed a breakthrough rapid cycling course and first-onset clinical hypothyroidism at the age of 31 years during lithium therapy. After levothyroxine augmentation therapy was introduced, the patient had remission from the rapid cycling illness course along with normalization of serum levels of free T4 and thyroid stimulating hormone in the subsequent year. This observation suggested that investigation of both levothyroxine pharmacology and thyroid pathology in male patients with rapid cycling bipolar disorder might be of much value. Keywords: mood disorder, therapy, thyroid hormone

Subchondral insufficiency fractures of the femoral head: associated imaging findings and predictors of clinical progression

Energy Technology Data Exchange (ETDEWEB)

Hackney, Lauren A.; Joseph, Gabby B.; Link, Thomas M. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Lee, Min Hee [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Vail, Thomas P. [University of California, Department of Orthopaedic Surgery, San Francisco, CA (United States)

2016-06-15

To characterize the morphology and imaging findings of femoral head subchondral insufficiency fractures (SIF), and to investigate clinical outcomes in relation to imaging findings. Fifty-one patients with hip/pelvis magnetic resonance (MR) images and typical SIF characteristics were identified and reviewed by two radiologists. Thirty-five patients had follow-up documentation allowing assessment of clinical outcome. Subgroup comparisons were performed using regression models adjusted for age and body mass index. SIF were frequently associated with cartilage loss (35/47, 74.5 %), effusion (33/42, 78.6 %), synovitis (29/44, 66 %), and bone marrow oedema pattern (BMEP) (average cross-sectional area 885.7 ± 730.2 mm{sup 2}). Total hip arthroplasty (THA) was required in 16/35 patients, at an average of 6 months post-MRI. Compared to the THA cohort, the non-THA group had significantly (p < 0.05) smaller overlying cartilage defect size (10 mm vs. 29 mm), smaller band length ratio and fracture diameters, and greater incidence of parallel fracture morphology (p < 0.05). Male gender and increased age were significantly associated with progression, p < 0.05. SIF were associated with synovitis, cartilage loss, effusion, and BMEP. Male gender and increased age had a significant association with progression to THA, as did band length ratio, fracture diameter, cartilage defect size, and fracture deformity/morphology. (orig.)

Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: Cessation of CTL responses is associated with disease progression

DEFF Research Database (Denmark)

Andersen, M.H.; Keikavoussi, P.; Brocker, E.B.

2001-01-01

Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease...... by Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical...

Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG)

DEFF Research Database (Denmark)

Rustin, Gordon John Sampson; Vergote, Ignace; Eisenhauer, Elizabeth

2011-01-01

. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal...... communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet......The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using...

Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death

DEFF Research Database (Denmark)

Casadellà, Maria; Cozzi-Lepri, Alessandro; Phillips, Andrew

2017-01-01

-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0...

The analysis of the clinical and tool parameters characterizing a cardiomyopathyat various forms of the progressing muscular dystrophies

Directory of Open Access Journals (Sweden)

Poverennova I.E.

2017-03-01

Full Text Available Purpose: studying of clinical and tool characteristics of cardiomyopathies at various forms of the progressing muscular dystrophies. Material and methods. There had been 103 patients with hereditary forms of the progressing muscular dystrophies examined, among which 35 persons were with Duchenne muscular dystrophy, 28 with an atrophic myo-tonia, and 40 with a limb girdle dystrophy is conducted. Assessment of clinical and tool features of cardiomyopathies at these types of the hereditary progressing muscular dystrophies had been carried out. Results. In the group of patients with diffusion damage of a myocardium in the form of dystrophic violations had been revealed. Existence of a negative tooth of T in some assignments and lengthenings of an interval of QT is noted. With a dystrophic myotonia violation of a warm rhythm occurred at patients by 87 times more often than in the group of comparison. Violation of a rhythm of heart in group of patients with a limb girdle dystrophy came to light 91 times more often in reference to the group of comparison. Conclusion. Violations in a cardiovascular system at Duchenne muscular dystrophy are preferentially diffusion changes in a myocardium. At a dystrophic myotonia and a limb girdle dystrophy cardial violations concern mainly excitability and the conductivity of heart which are the main reason of developing of this disease at these patients.

Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria.

Science.gov (United States)

Brown-Elliott, Barbara A; Wallace, Richard J

2002-10-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing.

A rapid MALDI-TOF MS identification database at genospecies level for clinical and environmental Aeromonas strains.

Directory of Open Access Journals (Sweden)

Cinzia Benagli

Full Text Available The genus Aeromonas has undergone a number of taxonomic and nomenclature revisions over the past 20 years, and new (subspecies and biogroups are continuously described. Standard identification methods such as biochemical characterization have deficiencies and do not allow clarification of the taxonomic position. This report describes the development of a matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS identification database for a rapid identification of clinical and environmental Aeromonas isolates.

Correlation between HIV-1 genotype and clinical progression in HIV/AIDS patients in Surabaya, Indonesia

Science.gov (United States)

Rachman, B. E.; Khairunisa, S. Q.; Witaningrum, A. M.; Yunifiar, M. Q.; Nasronudin

2018-03-01

Several factors such as host and viral factors can affect the progression of HIV/AIDS. This study aims to identify the correlation viral factors, especially the HIV-1 subtype with HIV/AIDS progression. Inpatient HIV/AIDS during the period March to September 2017 and willing to participate are included in the study. Historical data of disease and treatment was taken by medical record. Blood samples were amplified, sequenced and undergone phylogenetic analysis. Linear regression analysis was used to estimate beta coefficient (β) and 95%CI of HIV/AIDS progression (measured by the CD4 change rate, ΔCD4 cell count/time span in months).This study has 17 samples. The HIV-1 subtype was dominated by CRF01_AE (81.8%) followed by subtype B (18.2%). There was significant correlation between subtype HIV-1 (p = 0.04) and body mass index (p = 0.038) with HIV/AIDS clinical stage. Many factors were assumed to be correlated with increased rate of CD4, but we only subtype HIV-1 had a significant correlation (p = 0.024) with it. From multivariate analysis, we also found that subtype HIV-1 had a significant correlation (β = 0.788, 95%CI: 17.5-38.6, p = 0.004).

Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy

Directory of Open Access Journals (Sweden)

Juan C. Almagro

2018-01-01

Full Text Available The remarkable progress in engineering and clinical development of therapeutic antibodies in the last 40 years, after the seminal work by Köhler and Milstein, has led to the approval by the United States Food and Drug Administration (FDA of 21 antibodies for cancer immunotherapy. We review here these approved antibodies, with emphasis on the methods used for their discovery, engineering, and optimization for therapeutic settings. These methods include antibody engineering via chimerization and humanization of non-human antibodies, as well as selection and further optimization of fully human antibodies isolated from human antibody phage-displayed libraries and immunization of transgenic mice capable of generating human antibodies. These technology platforms have progressively led to the development of therapeutic antibodies with higher human content and, thus, less immunogenicity. We also discuss the genetic engineering approaches that have allowed isotype switching and Fc modifications to modulate effector functions and bioavailability (half-life, which together with the technologies for engineering the Fv fragment, have been pivotal in generating more efficacious and better tolerated therapeutic antibodies to treat cancer.

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

Directory of Open Access Journals (Sweden)

Jan A J G van den Brand

Full Text Available To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated.Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated.In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time.Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

Science.gov (United States)

van den Brand, Jan A J G; Mutsaers, Henricus A M; van Zuilen, Arjan D; Blankestijn, Peter J; van den Broek, Petra H; Russel, Frans G M; Masereeuw, Rosalinde; Wetzels, Jack F M

2016-01-01

To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

Progressive Multifocal Leukoencephalopathy

Science.gov (United States)

... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection ...

Progress on high-performance rapid prototype aluminum mirrors

Science.gov (United States)

Woodard, Kenneth S.; Myrick, Bruce H.

2017-05-01

Near net shape parts can be produced using some very old processes (investment casting) and the relatively new direct metal laser sintering (DMLS) process. These processes have significant advantages for complex blank lightweighting and costs but are not inherently suited for producing high performance mirrors. The DMLS process can provide extremely complex lightweight structures but the high residual stresses left in the material results in unstable mirror figure retention. Although not to the extreme intricacy of DMLS, investment casting can also provide complex lightweight structures at considerably lower costs than DMLS and even conventional wrought mirror blanks but the less than 100% density for casting (and also DMLS) limits finishing quality. This paper will cover the progress that has been made to make both the DMLS and investment casting processes into viable near net shape blank options for high performance aluminum mirrors. Finish and figure results will be presented to show performance commensurate with existing conventional processes.

White Matter Lesion Progression in LADIS

DEFF Research Database (Denmark)

Schmidt, Reinhold; Berghold, Andrea; Jokinen, Hanna

2012-01-01

BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample...... sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating...

Large-scale identification of clinical and genetic predictors of motor progression in patients with newly diagnosed Parkinson's disease: a longitudinal cohort study and validation.

Science.gov (United States)

Latourelle, Jeanne C; Beste, Michael T; Hadzi, Tiffany C; Miller, Robert E; Oppenheim, Jacob N; Valko, Matthew P; Wuest, Diane M; Church, Bruce W; Khalil, Iya G; Hayete, Boris; Venuto, Charles S

2017-11-01

Better understanding and prediction of progression of Parkinson's disease could improve disease management and clinical trial design. We aimed to use longitudinal clinical, molecular, and genetic data to develop predictive models, compare potential biomarkers, and identify novel predictors for motor progression in Parkinson's disease. We also sought to assess the use of these models in the design of treatment trials in Parkinson's disease. A Bayesian multivariate predictive inference platform was applied to data from the Parkinson's Progression Markers Initiative (PPMI) study (NCT01141023). We used genetic data and baseline molecular and clinical variables from patients with Parkinson's disease and healthy controls to construct an ensemble of models to predict the annual rate of change in combined scores from the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III. We tested our overall explanatory power, as assessed by the coefficient of determination (R 2 ), and replicated novel findings in an independent clinical cohort from the Longitudinal and Biomarker Study in Parkinson's disease (LABS-PD; NCT00605163). The potential utility of these models for clinical trial design was quantified by comparing simulated randomised placebo-controlled trials within the out-of-sample LABS-PD cohort. 117 healthy controls and 312 patients with Parkinson's disease from the PPMI study were available for analysis, and 317 patients with Parkinson's disease from LABS-PD were available for validation. Our model ensemble showed strong performance within the PPMI cohort (five-fold cross-validated R 2 41%, 95% CI 35-47) and significant-albeit reduced-performance in the LABS-PD cohort (R 2 9%, 95% CI 4-16). Individual predictive features identified from PPMI data were confirmed in the LABS-PD cohort. These included significant replication of higher baseline MDS-UPDRS motor score, male sex, and increased age, as well as a novel Parkinson's disease

Progressive multifocal leukoencephalopathy limited to the brain stem

Energy Technology Data Exchange (ETDEWEB)

Kastrup, O.; Maschke, M.; Diener, H.C. [Neurologische Universitaetsklinik, University of Essen (Germany); Wanke, I. [Department of Neuroradiology, University of Essen (Germany)

2002-03-01

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating slow-virus encephalitis caused by the JC polyomavirus in 2-5% of patients with AIDS. MRI typically shows multiple lesions in the cerebral hemispheres. We present a rare case of rapidly evolving and lethal PML with a severe bulbar syndrome and spastic tetraparesis in a patient with AIDS. MRI showed high-signal lesions on T2-weighted images confined to the brain stem, extending from the medulla oblongata to the midbrain. JC virus polymerase chain reaction in cerebrospinal fluid was positive, and neuropathology showed the findings of PML. This case was also notable because of the rapid progression despite improved immune status with antiretroviral therapy. (orig.)

Glaucoma Monitoring in a Clinical Setting Glaucoma Progression Analysis vs Nonparametric Progression Analysis in the Groningen Longitudinal Glaucoma Study

NARCIS (Netherlands)

Wesselink, Christiaan; Heeg, Govert P.; Jansonius, Nomdo M.

Objective: To compare prospectively 2 perimetric progression detection algorithms for glaucoma, the Early Manifest Glaucoma Trial algorithm (glaucoma progression analysis [GPA]) and a nonparametric algorithm applied to the mean deviation (MD) (nonparametric progression analysis [NPA]). Methods:

Rapid Detection of Herpes Viruses for Clinical Applications

Science.gov (United States)

Pierson, Duane; Mehta, Satish

2013-01-01

There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

Primary progressive aphasia and apraxia of speech.

Science.gov (United States)

Jung, Youngsin; Duffy, Joseph R; Josephs, Keith A

2013-09-01

Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: nonfluent/agrammatic, semantic, and logopenic variants. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. The clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech are reviewed in this article. The distinctions among these disorders for accurate diagnosis are increasingly important from a prognostic and therapeutic standpoint. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Metabonomics Research Progress on Liver Diseases.

Science.gov (United States)

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

Science.gov (United States)

Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

2015-01-01

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

Directory of Open Access Journals (Sweden)

Susan Morrison

Full Text Available During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART, despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

The Changing Role of the Clinical Microbiology Laboratory in Defining Resistance in Gram-negatives.

Science.gov (United States)

Endimiani, Andrea; Jacobs, Michael R

2016-06-01

The evolution of resistance in Gram-negatives has challenged the clinical microbiology laboratory to implement new methods for their detection. Multidrug-resistant strains present major challenges to conventional and new detection methods. More rapid pathogen identification and antimicrobial susceptibility testing have been developed for use directly on specimens, including fluorescence in situ hybridization tests, automated polymerase chain reaction systems, microarrays, mass spectroscopy, next-generation sequencing, and microfluidics. Review of these methods shows the advances that have been made in rapid detection of resistance in cultures, but limited progress in direct detection from specimens. Copyright © 2016 Elsevier Inc. All rights reserved.

Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

Directory of Open Access Journals (Sweden)

Katsuhisa Masaki

Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.

Science.gov (United States)

Peyro Saint Paul, Laure; Debruyne, Danièle; Bernard, Delphine; Mock, Donald M; Defer, Gilles L

2016-01-01

Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease. High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion. A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.

Photorefractive keratectomy (PRK) at 193 nm using an erodible mask: new developments and clinical progress

Science.gov (United States)

Gordon, Michael; Seiler, Theo; Carey, Joseph P.; Friedman, Marc D.; Johnsson, N. M. F.; King, Michael C.; Muller, David F.

1993-06-01

This paper reports on our progress using an erodible mask to perform photorefractive keratectomy (PRK) for the correction of myopic astigmatism. We describe modifications to the mask, the mask eye cup and the surgical microscope aimed at simplifying the procedure and improving the ergonomics of the hardware. We report the clinical results of the post-op exam for 20 patients who have undergone PRK for myopic astigmatism under a Phase IIA study. The results compare favorably with an earlier Phase IIA study for performing PRK with a computer-controlled iris. Most important, the clinical data show the absence of any significant corneal haze and no significant decrease in spectacle corrected visual acuity. Although more long term follow-up is needed, the preliminary results support the safety and effectiveness of using an erodible mask to perform PRK for myopic astigmatism.

Clinical Predictors of Progressive Hemorrhagic Injury in Children with Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Guangfu Di

2017-11-01

Full Text Available ObjectiveTraumatic brain injury (TBI occurs commonly in children. Repeat computed tomography (CT follow up of TBI patients is often scheduled to identify progressive hemorrhagic injury (PHI. However, the utility of repeated CT scans, especially in children with mild TBI [Glasgow Coma Scale (GCS scores of 13–15], has been debated. The purposes of the present study were to identify clinical predictors of PHI in children with mild TBI and to clarify relevant clinical factors via radiological examination.MethodsFrom 2014 to 2016, we retrospectively enrolled children <15 years of age with mild TBI. We recorded age, sex, GCS scores on admission, causes of head injury, timing of initial CT, any loss of consciousness, vomiting and seizure data, and type of TBI. Based on repeat CT findings, patients were dichotomized into either a PHI group or a non-PHI group. Also, clinical data were comparatively reviewed. Multivariate logistic regression analysis was used to identify clinical predictors of PHI.ResultsOf the 175 enrolled children, 15 (8.6% experienced PHI. Univariate analysis revealed that GCS score on admission, cause of head injury, vomiting, seizure, and TBI type were associated with PHI. Multivariate logistic regression analysis showed that a GCS score of 13 and epidural hemorrhage (EDH were independently associated with PHI (hazard ratio = 0.131, P = 0.018; hazard ratio = 6.612, P = 0.027, respectively.ConclusionA GCS score of 13 and EDH were associated with PHI. These factors should be considered when deciding whether to repeat CT on children with mild TBI.

Psychological functioning in primary progressive versus secondary progressive multiple sclerosis

DEFF Research Database (Denmark)

Vleugels, L; Pfennings, L E; Pouwer, F

1998-01-01

Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary...... progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years...... (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP...

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Directory of Open Access Journals (Sweden)

Irene Forno

Full Text Available Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Science.gov (United States)

Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R; Altieri, Dario C; Vaira, Valentina; Bosari, Silvano

2015-01-01

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

A rapid evidence-based service by librarians provided information to answer primary care clinical questions.

Science.gov (United States)

McGowan, Jessie; Hogg, William; Rader, Tamara; Salzwedel, Doug; Worster, Danielle; Cogo, Elise; Rowan, Margo

2010-03-01

A librarian consultation service was offered to 88 primary care clinicians during office hours. This included a streamlined evidence-based process to answer questions in fewer than 20 min. This included a contact centre accessed through a Web-based platform and using hand-held devices and computers with Web access. Librarians were given technical training in evidence-based medicine, including how to summarise evidence. To describe the process and lessons learned from developing and operating a rapid response librarian consultation service for primary care clinicians. Evaluation included librarian interviews and a clinician exit satisfaction survey. Clinicians were positive about its impact on their clinical practice and decision making. The project revealed some important 'lessons learned' in the clinical use of hand-held devices, knowledge translation and training for clinicians and librarians. The Just-in-Time Librarian Consultation Service showed that it was possible to provide evidence-based answers to clinical questions in 15 min or less. The project overcame a number of barriers using innovative solutions. There are many opportunities to build on this experience for future joint projects of librarians and healthcare providers.

[Clinical features, risk factors and progresses on treatment of recurrent Vogt-Koyanagi-Harada disease].

Science.gov (United States)

Jia, S S; Zhao, C; Liu, X S; Zhang, M F

2017-04-11

Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis associated with central nervous system, auditory, and integumentary manifestations. Clinically, VKH usually responds well to early aggressive glucocorticosteroid treatment and may be cured without any clinically significant sequelae. Some patients, however, may enter the chronic recurrent phase, which may result in marked loss of vision due to complications such as complicated cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly characterized by anterior uveitis associated with thickening of the choroid. Initial poor visual acuity, severe anterior chamber reaction, choroidal folds,rapid tapering of systemic corticosteroids or inadequate duration of treatment, and development of extraocular manifestations may be risk factors of disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as effective strategy for recurrence of VKH. The positive effects of other immunosuppressive agents and biologic agents on treatment of chronic recurrent and refractory VKH have been gradually recognized by the uveitis community. (Chin J Ophthalmol, 2017, 53: 317-320) .

Leukocyte scintigraphy: correlation of serial scintigraphic findings and clinical progression of inflammatory bowel disease

International Nuclear Information System (INIS)

Ho, Y.; Kelly, M.J.; Kaliff, V.

1997-01-01

Full text: This study was performed (a) to determine whether the clinical progress of individual patients with inflammatory bowel disease mirrored changes in leukocyte scans, and (b) to assess the reasons for significant discrepancies. Two nuclear medicine physicians reviewed 44 white cell scans in 20 consecutive patients (4 males, 18 females) who were referred for two or more leukocyte scans (using either the 111 In Oxine or 99m Tc HMPAO labelling methods) by three gastroenterologists between 1 January 1992 and 1 June 1996. The sequential scanpairs (range 2-18 months apart) were classified by consensus reading as showing no change, more severe or less severe disease. Questionnaires were sent to the referring gastroenterologists to determine whether the overall clinical status of each patient was unchanged, better or worse in the interval between the two scans. There was complete agreement between clinical and scintigraphic assessment in 45% (10/22) of the study pairs. Review of responses of the three individual gastroenterologists showed a wide range of agreement (4/4, 4/5, 2/13). Review of data showed that most disagreement was based on subjective clinical assessment, and hence of uncertain significance. In two patients, however, potentially preventable false negative leukocyte scans occurred in patients with active proctitis. This may be overcome by rigorous attention to ensure complete emptying of radioactivity from the bladder when 99m Tc HMPAO is used. It was concluded that serial leukocyte scans add to clinical assessment but careful technique is needed to avoid false negative scans in the rectum

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

Science.gov (United States)

Li, Min; Wang, Li; Liu, Jiang-Hong; Zhan, Shu-Qin

2018-01-01

Objective: Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources: Using the combined keywords: “RBD”, “neurodegenerative disease”, “Parkinson disease”, and “magnetic resonance imaging”, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection: A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results: Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated

Clinical management of rapidly growing mycobacterial cutaneous infections in patients after mesotherapy.

Science.gov (United States)

Regnier, Stéphanie; Cambau, Emmanuelle; Meningaud, Jean-Paul; Guihot, Amelie; Deforges, Lionel; Carbonne, Anne; Bricaire, François; Caumes, Eric

2009-11-01

Increasing numbers of patients are expressing an interest in mesotherapy as a method of reducing body fat. Cutaneous infections due to rapidly growing mycobacteria are a common complication of such procedures. We followed up patients who had developed cutaneous infections after undergoing mesotherapy during the period October 2006-January 2007. Sixteen patients were infected after mesotherapy injections performed by the same physician. All patients presented with painful, erythematous, draining subcutaneous nodules at the injection sites. All patients were treated with surgical drainage. Microbiological examination was performed on specimens that were obtained before and during the surgical procedure. Direct examination of skin smears demonstrated acid-fast bacilli in 25% of the specimens that were obtained before the procedure and 37% of the specimens obtained during the procedure; culture results were positive in 75% of the patients. Mycobacterium chelonae was identified in 11 patients, and Mycobacterium frederiksbergense was identified in 2 patients. Fourteen patients were treated with antibiotics, 6 received triple therapy as first-line treatment (tigecycline, tobramycin, and clarithromycin), and 8 received dual therapy (clarithromycin and ciprofloxacin). The mean duration of treatment was 14 weeks (range, 1-24 weeks). All of the patients except 1 were fully recovered 2 years after the onset of infection, with the mean time to healing estimated at 6.2 months (range, 1-15 months). This series of rapidly growing mycobacterial cutaneous infections highlights the difficulties in treating such infections and suggests that in vitro susceptibility to antibiotics does not accurately predict their clinical efficacy.

Rapidity resummation for B-meson wave functions

Directory of Open Access Journals (Sweden)

Shen Yue-Long

2014-01-01

Full Text Available Transverse-momentum dependent (TMD hadronic wave functions develop light-cone divergences under QCD corrections, which are commonly regularized by the rapidity ζ of gauge vector defining the non-light-like Wilson lines. The yielding rapidity logarithms from infrared enhancement need to be resummed for both hadronic wave functions and short-distance functions, to achieve scheme-independent calculations of physical quantities. We briefly review the recent progress on the rapidity resummation for B-meson wave functions which are the key ingredients of TMD factorization formulae for radiative-leptonic, semi-leptonic and non-leptonic B-meson decays. The crucial observation is that rapidity resummation induces a strong suppression of B-meson wave functions at small light-quark momentum, strengthening the applicability of TMD factorization in exclusive B-meson decays. The phenomenological consequence of rapidity-resummation improved B-meson wave functions is further discussed in the context of B → π transition form factors at large hadronic recoil.

Comparative assessment of the clinical and X-ray picture of urenic osteodystrophy before and after parathyroidectomy

International Nuclear Information System (INIS)

Ratobyl'skij, G.V.; Suslov, V.P.; Ivanov, I.A.; Loseva, T.V.

1992-01-01

The results of clinical, X-ray, and biochemical studies carried out in 51 patients with uremic osterodystrophy, treated with hemodialysis, before and after parathyroidectomy are presented. The patients were divided into 4 groups with various patterns of X-ray symptoms. Analysis of the clinical and X-ray data before and after parathyroidectomy has brought to a conclusion that such an intervention was effective only in cases with manifest clinical and X-ray symptoms of fibrous osteodystrophy. Surgical treatment is containdicated to patients in whom X-ray signs of osteomalacia predominate over fibrous osteodystrophy; it may result in a rap[id progress of osteomalacia

Progression of chronic renal failure.

Science.gov (United States)

Hakim, R M; Lazarus, J M

1989-11-01

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.

Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

Science.gov (United States)

Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

2013-08-01

One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. © 2013 International Society for Neurochemistry.

PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST.

Science.gov (United States)

Demetriou, Eleni; Tachrount, Mohamed; Zaiss, Moritz; Shmueli, Karin; Golay, Xavier

2018-03-05

To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T 1 of water and B 1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer-weighted imaging. Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo. © 2018 International Society for Magnetic Resonance in Medicine.

Outcomes of patients presenting to a dedicated rapid access lung cancer clinic.

LENUS (Irish Health Repository)

Dunican, E

2012-02-01

We examined the outcomes of the first 500 patients referred to a dedicated Rapid Access Lung Cancer Clinic. A total of 206 patients (41.2%) were diagnosed with a thoracic malignancy; 179 had primary lung cancer and 27 had secondary or other thoracic cancers. Pulmonary nodules requiring ongoing surveillance were found in a further 79 patients (15.8%). Of those patients found to have primary lung cancer, 24 (13.4%) had Small Cell and 145 (81%) had Non Small Cell Lung Cancer. In patients with Non small cell tumours, 26 (21.1%) were stage 1, 14 (11.4%) stage II, 37 (30.1%) stage III and 46 (37.4%) stage IV at diagnosis. For the 129 patients (72%) in whom the thoracic MDT recommended active treatment, primary therapy was surgical resection in 44 (24.6%), combined chemoradiation in 31 patients (17.3%), chemotherapy alone in 39 (21.8%) and radiation in 15 (8.4%).

A warning to the Brazilian Speech-Language Pathology and Audiology community about the importance of scientific and clinical activities in primary progressive aphasia.

Science.gov (United States)

Beber, Bárbara Costa; Brandão, Lenisa; Chaves, Márcia Lorena Fagundes

2015-01-01

This article aims to warn the Brazilian Speech-Language Pathology and Audiology scientific community about the importance and necessity of scientific and clinical activities regarding Primary Progressive Aphasia. This warning is based on a systematic literature review of the scientific production on Primary Progressive Aphasia, from which nine Brazilian articles were selected. It was observed that there is an obvious lack of studies on the subject, as all the retrieved articles were published in medical journals and much of it consisted of small samples; only two articles described the effectiveness of speech-language therapy in patients with Primary Progressive Aphasia. A perspective for the future in the area and characteristics of Speech-Language Therapy for Primary Progressive Aphasia are discussed. As a conclusion, it is evident the need for greater action by Speech-Language Pathology and Audiology on Primary Progressive Aphasia.

Progressive outer retinal necrosis presenting as cherry red spot.

Science.gov (United States)

Yiu, Glenn; Young, Lucy H

2012-10-01

To report a case of progressive outer retinal necrosis (PORN) presenting as a cherry red spot. Case report. A 53-year-old woman with recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis developed rapid sequential vision loss in both eyes over 2 months. Her exam showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary changes, consistent with PORN. Due to her late presentation and the rapid progression of her condition, she quickly developed end-stage vision loss in both eyes. PORN should be considered within the differential diagnosis of a "cherry red spot." Immune-deficient patients with a history of herpetic infection who present with visual loss warrant prompt ophthalmological evaluation.

Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.

Directory of Open Access Journals (Sweden)

Josh Hanson

Full Text Available Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone.We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage.If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI 97.8-99.9 and for survival to discharge 96.9% (95% CI 94.3-98.5. In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100 and to discharge was 98.5% (95% CI 94.8-99.8.Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

Progression of motor symptoms in Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Ruiping Xia; Zhi-Hong Mao

2012-01-01

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity,bradykinesia and tremor - due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsenirtg symptoms.However,the drug-induced involuntary body movements and motor comphcations can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

Tracking Clean Energy Progress 2013

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-06-01

Tracking Clean Energy Progress 2013 (TCEP 2013) examines progress in the development and deployment of key clean energy technologies. Each technology and sector is tracked against interim 2020 targets in the IEA Energy Technology Perspectives 2012 2°C scenario, which lays out pathways to a sustainable energy system in 2050. Stark message emerge: progress has not been fast enough; large market failures are preventing clean energy solutions from being taken up; considerable energy efficiency remains untapped; policies need to better address the energy system as a whole; and energy-related research, development and demonstration need to accelerate. Alongside these grim conclusions there is positive news. In 2012, hybrid-electric vehicle sales passed the 1 million mark. Solar photovoltaic systems were being installed at a record pace. The costs of most clean energy technologies fell more rapidly than anticipated.

Constriction of juxta-ductal aorta and rapid progression of obstruction in a newborn

International Nuclear Information System (INIS)

Awasthy, Neeraj; Tomar, Munesh; Radhakrishnan, Sitaraman; Iyer, Krishna Subramoney

2010-01-01

A 13-day-old baby girl presenting with features of congestive cardiac failure was found to have coarctation of the aorta (CoA) and patent ductus arteriosus (PDA) by echocardiography. Doppler spectral display revealed moderate CoA. Echocardiogram, 12 hours later, showed severe juxtaductal aortic coarctation with spontaneous closure of PDA. This case emphasises the need to keep a close watch on the progress of CoA in the neonatal period, even if the duct has narrowed to a small size thus demonstrating the role of constriction of juxtaductal aorta in pathogenesis of coaractation. Closure of even asmall PDA can cause acute progression CoA in the presence of posterior shelf

Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

Energy Technology Data Exchange (ETDEWEB)

Zieger, A.; Vonofakos, D.; Vitzthum, H.

1981-12-01

The computerized tomogram (CT) of a senile case of Creutzfeldt-Jacob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - suggest the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes.

Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

International Nuclear Information System (INIS)

Zieger, A.

1981-01-01

The computerized tomogram (CT) of a senile case of Creutzfeldt-Jakob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - let appear probable the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes. (orig./MG) [de

Chronic Subdural Hematoma development in Accelerated phase of Chronic Myeloid Leukaemia presenting with seizure and rapid progression course with fatal outcome

Directory of Open Access Journals (Sweden)

Raheja Amol

2015-06-01

Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy

The effectiveness of electromagnetic terahertz radiation use in the treatment of patients with rapidly progressive periodontitis

Directory of Open Access Journals (Sweden)

Zelenova A.V.

2015-12-01

Full Text Available The aim: to increase the efficiency of treatment of patients with rapidly progressive periodontitis (RPP using electromagnetic radiation at terahertz frequencies of molecular spectrum of radiation and absorption of nitric oxide 150,176-150,664 GHz. Material and methods. The study involved 50 patients with RPP, which according to the method of therapy were divided into 2 groups: group 1 included patients receiving conventional therapy, group 2 consisted of patients who, along with traditional therapy received EHF-therapy device "Orbit" YAKUL.941526.001. The control group consisted of 20 healthy subjects with intact periodontium. For the non-invasive study of tissue blood flow in the periodontal tissue Doppler ultrasound was used MiniMax-Doppler-Phono. The study of the microvasculature of periodontitis has been conducted. To determine the reactivity of microvascular periodontal tissue reflex functional tests on the indirect effect of the cold were performed. Results. Reductions achieved values of periodontal indices, especially important index PMA, a significant increase in the linear blood flow indices, decreased pulse pressure gradient and the index followed appropriate reduction to their cold test. Conclusion. The proposed complex therapy can accelerate the relief of inflammation in the periodontal tissues of the complex, to improve the elastic properties of blood vessels, reduce their tone and restore microcirculation in periodontal tissues.

Progress in Early Childhood Caries and Opportunities in Research, Policy, and Clinical Management

DEFF Research Database (Denmark)

Garcia, Raul; Borrelli, Belinda; Dhar, Vineet

2015-01-01

The 2014 Early Childhood Caries Conference encompassed evidence-based reviews on the state of the science regarding early childhood carries (ECC) epidemiology, etiology, prevention, and disease management. The purpose of this paper was to discuss the work presented at the conference and identify...... means to prevent and manage ECC. Analyses of studies indicate that some approaches, such as chlorhexidine, iodine, and remineralizing agents, have not shown consistent findings in preventing ECC. However, evidence exists to yield recommendations in some areas. There are useful risk assessment indicators...... opportunities in research, policy, and clinical management that may improve early childhood caries outcomes and lower costs of care. While great progress has been made since the 1997 ECC Conference, there remains a paucity of high-quality evidence from randomized controlled trials on what are the most effective...

The Clinical Presentation of Mitochondrial Diseases in Children with Progressive Intellectual and Neurological Deterioration: A National, Prospective, Population-Based Study

Science.gov (United States)

Verity, Christopher M.; Winstone, Anne Marie; Stellitano, Lesley; Krishnakumar, Deepa; Will, Robert; McFarland, Robert

2010-01-01

Aim: Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method: Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card…

PCR-RFLP on β-tubulin gene for rapid identification of the most clinically important species of Aspergillus.

Science.gov (United States)

Nasri, Tuba; Hedayati, Mohammad Taghi; Abastabar, Mahdi; Pasqualotto, Alessandro C; Armaki, Mojtaba Taghizadeh; Hoseinnejad, Akbar; Nabili, Mojtaba

2015-10-01

Aspergillus species are important agents of life-threatening infections in immunosuppressed patients. Proper speciation in the Aspergilli has been justified based on varied fungal virulence, clinical presentations, and antifungal resistance. Accurate identification of Aspergillus species usually relies on fungal DNA sequencing but this requires expensive equipment that is not available in most clinical laboratories. We developed and validated a discriminative low-cost PCR-based test to discriminate Aspergillus isolates at the species level. The Beta tubulin gene of various reference strains of Aspergillus species was amplified using the universal fungal primers Bt2a and Bt2b. The PCR products were subjected to digestion with a single restriction enzyme AlwI. All Aspergillus isolates were subjected to DNA sequencing for final species characterization. The PCR-RFLP test generated unique patterns for six clinically important Aspergillus species, including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus terreus, Aspergillus clavatus and Aspergillus nidulans. The one-enzyme PCR-RFLP on Beta tubulin gene designed in this study is a low-cost tool for the reliable and rapid differentiation of the clinically important Aspergillus species. Copyright © 2015 Elsevier B.V. All rights reserved.

Possibility of Integrated Data Mining of Clinical Data

Directory of Open Access Journals (Sweden)

Akinori Abe

2007-03-01

Full Text Available In this paper, we introduce integrated data mining. Because of recent rapid progress in medical science as well as clinical diagnosis and treatment, integrated and cooperative research among medical researchers, biology, engineering, cultural science, and sociology is required. Therefore, we propose a framework called Cyber Integrated Medical Infrastructure (CIMI. Within this framework, we can deal with various types of data and consequently need to integrate those data prior to analysis. In this study, for medical science, we analyze the features and relationships among various types of data and show the possibility of integrated data mining.

Poverty Reduction and Shared Prosperity in Moldova : Progress and Prospects

OpenAIRE

World Bank Group

2016-01-01

Moldova has experienced rapid economic growth in the past decade, which has been accompanied by reductions in poverty and good performance in shared prosperity. Nonetheless, Moldova remains one of the poorest countries in Europe and faces challenges in sustaining the progress. The challenges for progress include spatial and cross-group inequalities, particularly because of unequal access t...

Constriction of juxta-ductal aorta and rapid progression of obstruction in a newborn

Directory of Open Access Journals (Sweden)

Awasthy Neeraj

2010-01-01

Full Text Available A 13-day-old baby girl presenting with features of congestive cardiac failure was found to have coarctation of the aorta (CoA and patent ductus arteriosus (PDA by echocardiography. Doppler spectral display revealed moderate CoA. Echocardiogram, 12 hours later, showed severe juxtaductal aortic coarctation with spontaneous closure of PDA. This case emphasises the need to keep a close watch on the progress of CoA in the neonatal period, even if the duct has narrowed to a small size thus demonstrating the role of constriction of juxtaductal aorta in pathogenesis of coaractation. Closure of even asmall PDA can cause acute progression CoA in the presence of posterior shelf.

Rapid promotion and progression of fibrovascular polyps by inflammation and/or hyperplasia in hamster check pouch: implications for carcinogenesis assay.

Science.gov (United States)

McGaughey, C; Jensen, J L

1983-03-01

Tumor initiation by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in dimethyl sulfoxide (DMSO) followed by topical application of retinyl acetate (RA), ethylphenylpropiolate, or acetic acid in DMSO at inflammatory and hyperplasiogenic dose regimens caused the rapid promotion of fibrovascular polyps with dysplastic epithelium in hamster cheek pouch. Such lesions did not occur in control animals initiated with DMBA followed by application of DMSO only, where inflammation was also minimal. At the dose regimen employed, RA caused obvious cytotoxicity and tissue destruction. With EPP and AA, there was no histological evidence of tissue destruction. At dose regimens resulting in minimal inflammation and no apparent cytotoxicity, RA promoted almost no polyps, but a higher yield of other tumor types. Thus, inflammation and/or hyperplasia apparently exerted a strong polyp-promoting and progressive influence. This and other differences between the tumorigenic responses of hamster-pouch mucosa and mouse skin suggest that the former supplement the latter in carcinogenic risk assessment.

TGF-β in pancreatic cancer initiation and progression: two sides of the same coin.

Science.gov (United States)

Shen, Wei; Tao, Guo-Qing; Zhang, Yu; Cai, Bing; Sun, Jian; Tian, Zhi-Qiang

2017-01-01

Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.

Rapid response systems.

Science.gov (United States)

Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

2018-07-01

Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.

Progressive neuronal degeneration of childhood with liver disease

International Nuclear Information System (INIS)

Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

1987-01-01

The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

Multiple gingival pregnancy tumors with rapid growth

Directory of Open Access Journals (Sweden)

Wei-Lian Sun

2014-09-01

Full Text Available Pregnancy gingivitis is an acute form of gingivitis that affects pregnant women, with a prevalence of 30%, possibly ranging up to 100%. Sometimes, pregnancy gingivitis shows a tendency toward a localized hyperplasia called gingival pyogenic granuloma. Pregnancy tumor is a benign gingival hyperplasia with the gingiva as the most commonly involved site, but rarely it involves almost the entire gingiva. A 22-year-old woman was referred to our clinic with a chief complaint of gingival swelling that had lasted for 2 days. The lesions progressed rapidly and extensively, and almost all the gingiva was involved a week later. Generalized erythema, edema, hyperplasia, a hemorrhagic tendency, and several typical hemangiomatous masses were noted. Pregnancy was denied by the patient at the first and second visits, but was confirmed 2 weeks after the primary visit. The patient was given oral hygiene instructions. She recovered well, and the mass gradually regressed and had disappeared completely at the end of 12 weeks of pregnancy, without recurrence. The gingival lesions were finally diagnosed as multiple gingival pregnancy tumors. The patient delivered a healthy infant. An extensive and rapid growth of gingival pregnancy tumors during the early first month of pregnancy is a rare occurrence that is not familiar to dentists, gynecologists, and obstetricians. Those practitioners engaged in oral medicine and periodontology, primary care obstetrics, and gynecology should be aware of such gingival lesions to avoid misdiagnosis and overtreatment.

The semantic variant of primary progressive aphasia: clinical and neuroimaging evidence in single subjects.

Directory of Open Access Journals (Sweden)

Leonardo Iaccarino

Full Text Available We present a clinical-neuroimaging study in a series of patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA, with the aim to provide clinical-functional correlations of the cognitive and behavioral manifestations at the single-subject level.We performed neuropsychological investigations, 18F-FDG-PET single-subject and group analysis, with an optimized SPM voxel-based approach, and correlation analyses. A measurement of white matter integrity by means of diffusion tensor imaging (DTI was also available for a subgroup of patients.Cognitive assessment confirmed the presence of typical semantic memory deficits in all patients, with a relative sparing of executive, attentional, visuo-constructional, and episodic memory domains. 18F-FDG-PET showed a consistent pattern of cerebral hypometabolism across all patients, which correlated with performance in semantic memory tasks. In addition, a majority of patients also presented with behavioral disturbances associated with metabolic dysfunction in limbic structures. In a subgroup of cases the DTI analysis showed FA abnormalities in the inferior longitudinal and uncinate fasciculi.Each svPPA individual had functional derangement involving an extended, connected system within the left temporal lobe, a crucial part of the verbal semantic network, as well as an involvement of limbic structures. The latter was associated with behavioral manifestations and extended beyond the area of atrophy shown by CT scan.Single-subject 18F-FDG-PET analysis can account for both cognitive and behavioral alterations in svPPA. This provides useful support to the clinical diagnosis.

Clinical features, management and outcomes of progressive outer retinal necrosis (PORN) in southern Thailand.

Science.gov (United States)

Sittivarakul, Wantanee; Aui-aree, Nipat

2009-03-01

To study the demographics, clinical features, treatment, and visual outcomes of progressive outer retinal necrosis (PORN) in a group of Thai patients. All cases of AIDS with a clinical diagnosis of PORN in a major tertiary referral hospital in southern Thailand between January 2003 and June 2007 were retrospectively reviewed. Demographic data, clinical features, treatment regimens, and visual outcomes were analyzed. Seven patients (11 eyes) were studied. The mean age was 44.7 years. The median CD4 count was 12 cells/mm3. A known history of cutaneous zoster was documented in 57% of cases. The median follow-up period was 17 weeks. Fifty-seven percent of the patients had bilateral disease. A majority of eyes (45.4%) had initial visual acuity of less than 20/50 to equal to or better than 20/200. About two-thirds of the eyes had anterior chamber cells. Vitritis and retinal lesions scattered throughout both posterior pole and peripheral retina were found in 72.7%. Either intravenous acyclovir in combination with intravitreal ganciclovir injections or intravenous aclyclovir alone was used for initial treatment. Retinal detachment occurred in 54.5%. Final visual acuity worsened (loss of 3 lines on the ETDRS chart or more) in 60%. Visual acuity was no light perception in 45.5% at the final recorded follow-up. Demographics, clinical features and treatment outcomes of PORN in this group of Thai patients were comparable with studies from other countries. Visual prognosis is still poor with current treatment regimens.

SU-F-P-30: Clinical Assessment of Auto Beam-Hold Triggered by Fiducial Localization During Prostate RapidArc Delivery

Energy Technology Data Exchange (ETDEWEB)

Atkinson, P; Chen, Q [Flower Hospital, Sylvania, OH (United States)

2016-06-15

Purpose: To assess the clinical efficacy of auto beam hold during prostate RapidArc delivery, triggered by fiducial localization on kV imaging with a Varian True Beam. Methods: Prostate patients with four gold fiducials were candidates in this study. Daily setup was accomplished by aligning to fiducials using orthogonal kV imaging. During RapidArc delivery, a kV image was automatically acquired with a momentary beam hold every 60 degrees of gantry rotation. The position of each fiducial was identified by a search algorithm and compared to a predetermined 1.4 cm diameter target area. Treatment continued if all the fiducials were within the target area. If any fiducial was outside the target area the beam hold was not released, and the operators determined if the patient needed re-alignment using the daily setup method. Results: Four patients were initially selected. For three patients, the auto beam hold performed seamlessly. In one instance, the system correctly identified misaligned fiducials, stopped treatment, and the patient was re-positioned. The fourth patient had a prosthetic hip which sometimes blocked the fiducials and caused the fiducial search algorithm to fail. The auto beam hold was disabled for this patient and the therapists manually monitored the fiducial positions during treatment. Average delivery time for a 2-arc fraction was increased by 59 seconds. Phantom studies indicated the dose discrepancy related to multiple beam holds is <0.1%. For a plan with 43 fractions, the additional imaging increased dose by an estimated 68 cGy. Conclusion: Automated intrafraction kV imaging can effectively perform auto beam holds due to patient movement, with the exception of prosthetic hip patients. The additional imaging dose and delivery time are clinically acceptable. It may be a cost-effective alternative to Calypso in RapidArc prostate patient delivery. Further study is warranted to explore its feasibility under various clinical conditions.

SU-F-P-30: Clinical Assessment of Auto Beam-Hold Triggered by Fiducial Localization During Prostate RapidArc Delivery

International Nuclear Information System (INIS)

Atkinson, P; Chen, Q

2016-01-01

Purpose: To assess the clinical efficacy of auto beam hold during prostate RapidArc delivery, triggered by fiducial localization on kV imaging with a Varian True Beam. Methods: Prostate patients with four gold fiducials were candidates in this study. Daily setup was accomplished by aligning to fiducials using orthogonal kV imaging. During RapidArc delivery, a kV image was automatically acquired with a momentary beam hold every 60 degrees of gantry rotation. The position of each fiducial was identified by a search algorithm and compared to a predetermined 1.4 cm diameter target area. Treatment continued if all the fiducials were within the target area. If any fiducial was outside the target area the beam hold was not released, and the operators determined if the patient needed re-alignment using the daily setup method. Results: Four patients were initially selected. For three patients, the auto beam hold performed seamlessly. In one instance, the system correctly identified misaligned fiducials, stopped treatment, and the patient was re-positioned. The fourth patient had a prosthetic hip which sometimes blocked the fiducials and caused the fiducial search algorithm to fail. The auto beam hold was disabled for this patient and the therapists manually monitored the fiducial positions during treatment. Average delivery time for a 2-arc fraction was increased by 59 seconds. Phantom studies indicated the dose discrepancy related to multiple beam holds is <0.1%. For a plan with 43 fractions, the additional imaging increased dose by an estimated 68 cGy. Conclusion: Automated intrafraction kV imaging can effectively perform auto beam holds due to patient movement, with the exception of prosthetic hip patients. The additional imaging dose and delivery time are clinically acceptable. It may be a cost-effective alternative to Calypso in RapidArc prostate patient delivery. Further study is warranted to explore its feasibility under various clinical conditions.

Clinical monitoring of tooth wear progression in patients over a period of one year using CAD/CAM

OpenAIRE

Ahmed, Khaled E.; Whitters, John; Ju, Xiangyang; Pierce, S. Gareth; MacLeod, Charles N.; Murray, Colin A.

2017-01-01

Purpose: The aim of this study was to clinically monitor the progression of tooth wear over a period of 1 year in a cohort of referred tooth wear patients through the use of a computer-aided design/ computer-assisted manufacture (CAD/CAM) scanner and a standardized scanning/assessment methodology. Materials and Methods: Polyether impressions were made of 11 participants (130 teeth) at baseline and at 1 year. Impressions were poured in type IV dental stone and the anterior teeth were 3D scanne...

Loop-mediated isothermal amplification assay for rapid and sensitive detection of sheep pox and goat pox viruses in clinical samples.

Science.gov (United States)

Venkatesan, G; Balamurugan, V; Bhanuprakash, V; Singh, R K; Pandey, A B

2016-06-01

A Loop-mediated isothermal amplification (LAMP) assay targeting the highly conserved DNA polymerase gene of capripox virus genome was developed and evaluated for rapid detection of sheep pox and goat pox viruses. The optimized LAMP assay is found specific and sensitive for amplification of target DNA with a diagnostic sensitivity and specificity of 96.6% and 100% respectively compared to quantitative PCR. The detection rate of LAMP, PCR and Q-PCR assays is found to be 81.5%, 67% and 83% respectively. This LAMP assay has the potential for rapid clinical diagnosis and surveillance of sheep pox and goat pox in field diagnostic laboratories. Copyright © 2016 Elsevier Ltd. All rights reserved.

Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

Science.gov (United States)

Teng, Christopher C; De Moraes, Carlos Gustavo V; Prata, Tiago S; Tello, Celso; Ritch, Robert; Liebmann, Jeffrey M

2010-05-01

Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; Pzone PPA (HR, 2.59; P1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (zone PPA (kappa = 0.13). Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Colloid cysts of the third ventricle exhibit heterogeneous clinical picture

Directory of Open Access Journals (Sweden)

Janez Ravnik

2014-08-01

Full Text Available Background: Colloid cysts are rare benign intracranial tumours generally occurring in the front part of the third ventricle. Clinical picture may be non-specific. Various problems are usually associated with hydrocephalus that these cysts may cause.Methods: Five patients with colloid cyst of the third ventricle were consecutively operated on at our department. All had different clinical pictures. Two patients suffered from acute hydrocephalus, one of them also from rapid deterioration of consciousness. In two patients, the cyst was discovered accidentally owing to non-specific problems. One patient experienced progressive deterioration due to chronic hydrocephalus.Results: All patients had a colloid cyst removed via the right anterior interhemispheric transcallosal approach. One patient had surgical complication with transient left-sided haemiparesis, followed by osteomyelitis. Postoperative course in all other patients was unremarkable.Conclusions: Due to a high risk of potential sudden deterioration the colloid cysts may cause, a rapid surgical intervention is generally needed. The anterior interhemispheric transcallosal approach is a well accepted and safe surgical option.

Slowly progressive fluent aphasia; Clinical features and an imaging study including MRI, SPECT and PET

Energy Technology Data Exchange (ETDEWEB)

Sakurai, Yasuhisa; Momose, Toshimitsu; Watanabe, Toshiaki; Ishikawa, Takashi; Iwata, Makoto (Tokyo Univ. (Japan). Faculty of Medicine); Bando, Mitsuaki

1991-05-01

Three patients with slowly progressive fluent aphasia are reported. One of the patients presented with memory disturbance. They were characterized clinically by having selective deficits in vocabulary, which resulted in impairment of confrontation naming, and auditory comprehension. MRI showed an atrophy not only in the left temporal lobe (including the superior, middle and inferior temporal gyri), hippocampus, parahippocampual gyrus, and fusiform gyrus, but also in the left parietal lobe. I-123 IMP SPECT and F-18 FDG PET were used to determine regional cerebral blood flow and regional cerebral metabolic rate, respectively. In addition to the decreased tracer uptake in the left temporal and/or parietal lobe, a decreased uptake was seen in the bilateral basal ganglia, the inner side of the temporal lobe (including the bilateral hippocampus), the right anterior temporal lobe, and the left thalamus. These findings may deny the previous thought that lesions are localized in slowly progressive fluent aphasia. Furthermore, noticeable difficulty in naming, i.e., patients unable to recognize the right answer, are considered attributable to widespread lesions from the whole left temporal lobe, including the hippocampus, to the right temporal lobe. (N.K.).

Demyelination versus remyelination in progressive multiple sclerosis

DEFF Research Database (Denmark)

Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

Diagnostic performance of a rapid in-clinic test for the detection of Canine Parvovirus under different storage conditions and vaccination status.

Science.gov (United States)

Kantere, Maria C; Athanasiou, Labrini V; Spyrou, Vassiliki; Kyriakis, Constantinos S; Kontos, Vassilios; Chatzopoulos, Dimitrios C; Tsokana, Constantina N; Billinis, Charalambos

2015-04-01

Canine parvovirus (CPV) is one of the most common causes of acute haemorrhagic enteritis in young dogs, while clinical diagnosis is often indecisive. The aim of our study was to evaluate the diagnostic accuracy of an in-clinic rapid test in the detection of CPV infection in dogs. To this end, we compared the Rapid Diagnostic Kit of Canine Parvovirus, Coronavirus and Rotavirus antigen (Quicking(®)) to PCR, which is considered as the most reliable diagnostic method. A total of 78 duplicated faecal samples were collected from diarrhoeic dogs. Vaccination history within a month prior to the onset of diarrhoea was reported for 12 of the sampled dogs. The rapid diagnostic test was performed in 23 of the faecal samples directly, while the rest were placed into a sterile cotton tipped swab suitable for collection and transportation of viruses (Sigma Σ-VCM(®)) and stored at -20 °C. The sensitivity of the Quicking rapid diagnostic test compared to PCR in the total number of samples, in samples from non-vaccinated dogs and in samples tested directly after collection were 22.22% (95% CI: 13.27-33.57%), 26.67% (95% CI: 16.08-39.66%) and 76.47% (95% CI: 50.10-93.04%) respectively, while the specificity of the test was 100% in any case. In conclusion, negative results do not exclude parvoenteritis from the differential diagnosis, especially in dogs with early vaccination history, but a positive result almost certainly indicates CPV infection. An improved sensitivity may be expected when the test is performed immediately. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid sideline performance meets outpatient clinic: Results from a multidisciplinary concussion center registry.

Science.gov (United States)

Kyle Harrold, G; Hasanaj, Lisena; Moehringer, Nicholas; Zhang, Isis; Nolan, Rachel; Serrano, Liliana; Raynowska, Jenelle; Rucker, Janet C; Flanagan, Steven R; Cardone, Dennis; Galetta, Steven L; Balcer, Laura J

2017-08-15

This study investigated the utility of sideline concussion tests, including components of the Sports Concussion Assessment Tool, 3rd Edition (SCAT3) and the King-Devick (K-D), a vision-based test of rapid number naming, in an outpatient, multidisciplinary concussion center treating patients with both sports-related and non-sports related concussions. The ability of these tests to predict clinical outcomes based on the scores at the initial visit was evaluated. Scores for components of the SCAT3 and the K-D were fit into regression models accounting for age, gender, and sport/non-sport etiology in order to predict clinical outcome measures including total number of visits to the concussion center, whether the patient reached a SCAT3 symptom severity score≤7, and the total types of referrals each patient received over their course. Patient characteristics, differences between those with sport and non-sport etiologies, and correlations between the tests were also analyzed. Among 426 patients with concussion, SCAT3 total symptom score and symptom severity score at the initial visit predicted each of the clinical outcome variables. K-D score at the initial visit predicted the total number of visits and the total number of referrals. Those with sports-related concussions were younger, had less severely-affected test scores, had fewer visits and types of referrals, and were more likely to have clinical resolution of their concussion and to reach a symptom severity score≤7. This large-scale study of concussion patients supports the use of sideline concussion tests as part of outpatient concussion assessment, especially the total symptom and symptom severity score portions of the SCAT3 and the K-D. Women in this cohort had higher total symptom and symptom severity scores compared to men. Our data also suggest that those with non-sports-related concussions have longer lasting symptoms than those with sports-related concussions, and that these two groups should perhaps be

An assessment of treatment guidelines, clinical practices, demographics, and progression of disease among patients with amyotrophic lateral sclerosis in Japan, the United States, and Europe.

Science.gov (United States)

Takei, Koji; Tsuda, Kikumi; Takahashi, Fumihiro; Hirai, Manabu; Palumbo, Joseph

2017-10-01

There is an increasing clinical research focus on neuroprotective agents in amyotrophic lateral sclerosis (ALS). However, it is unclear how generalisable clinical study trial results are between different countries and regions. To assess similarities and differences in clinical practice and treatment guidelines for ALS, and also to compare the demographics and rate of progression of disease in patients with ALS enrolled in clinical trials in Japan, the US, and Europe. We performed a review of clinical studies published since 2000 to compare the demographics and characteristics of patients with ALS. Progression of ALS disease was assessed in patients receiving placebo. The changes per month in ALSFRS-R score were calculated and compared between the studies. Overall, diagnostic criteria, recognition of ALS symptoms, comorbidities, use of riluzole, and nutritional, and respiratory support were similar. Regarding demographics and characteristics, there were no clear differences in the incidence of sporadic ALS (range 91-98%), bulbar onset (range 11-41%), and median time from onset to diagnosis (range 9-14 months) among the populations despite the difference in race between regions. However, use of tracheostomy-based invasive respiratory support was higher in Japan (29-38%) than in the US (4%) and Europe (1-31%). Rate of progression of disease was similar between the US and Europe study populations (range -0.89 to -1.60 points/month), and the Japanese study populations (range -1.03 to -1.21 points/month). There is evidence to support the generalisability of data from the Japanese ALS trial experience to the US and Europe populations in early to mid-stage of ALS.

Clinical profile, outcomes, and progression to type 2 diabetes among Indian women with gestational diabetes mellitus seen at a diabetes center in south India

Directory of Open Access Journals (Sweden)

Manni Mohanraj Mahalakshmi

2014-01-01

Full Text Available Aim: To describe the clinical profile, maternal and fetal outcomes, and the conversion rates to diabetes in women with gestational diabetes mellitus (GDM seen at a tertiary care diabetes center in urban south India. Materials and Methods: Clinical case records of 898 women with GDM seen between 1991 and 2011 were extracted from the Diabetes Electronic Medical Records (DEMR of a tertiary care diabetes center in Chennai, south India and their clinical profile was analyzed. Follow-up data of 174 GDM women was available. To determine the conversion rates to diabetes, oral glucose tolerance test (OGTT was done in these women. Glucose tolerance status postpartum was classified based on World Health Organization (WHO 2006 criteria. Results: The mean maternal age of the women was 29 ± 4 years and mean age of gestation at first visit were 24 ± 8.4 weeks. Seventy percent of the women had a family history of diabetes. Seventy-eight percent of the women delivered full-term babies and 65% underwent a cesarean section. The average weight gain during pregnancy was 10.0 ± 4.2 kg. Macrosomia was present in 17.9% of the babies, hypoglycemia in 10.4%, congenital anomalies in 4.3%, and the neonatal mortality rate was 1.9%. Mean follow-up duration of the 174 women of whom outcome data was available was 4.5 years. Out of the 174, 101 women who were followed-up developed diabetes, of whom half developed diabetes within 5 years and over 90%, within 10 years of the delivery. Conclusions: Progression to type 2 diabetes mellitus (T2DM in Indian women with GDM is rapid. There is an urgent need to develop standardized protocols for GDM care in India that can improve the maternal and fetal outcomes and help prevent future diabetes in women with GDM.

FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases

Directory of Open Access Journals (Sweden)

Holmerová Iva

2011-05-01

Full Text Available Abstract Background Frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP that may be associated with motor neuron disease (FTLD-MND; involvement of extrapyramidal and other systems has also been reported. Case presentation We present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC. Conclusions Association of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome.

Disability in progressive MS is associated with T2 lesion changes

DEFF Research Database (Denmark)

Ammitzbøll, Cecilie; Dyrby, Tim Bjørn; Lyksborg, Mark

2017-01-01

Background: Progressive multiple sclerosis (MS) is characterized by diffuse changes on brain magnetic resonance imaging (MRI), which complicates the use of MRI as a diagnostic and prognostic marker. The relationship between MRI measures (conventional and non-conventional) and clinical disability...... in progressive MS therefore warrants further investigation. Objective: To investigate the relationship between clinical disability and MRI measures in patients with progressive MS. Methods: Data from 93 primary and secondary progressive MS patients who had participated in 3 phase 2 clinical trials were included...... matter. Disability was assessed by the Expanded Disability Status Scale (EDSS) and the MS functional composite. Results: T2 lesion volume was associated with impairment by all clinical measures. MD and MTR in T2 lesions were significantly related to disability, and lower FA values correlated with worse...

Real-time patient survey data during routine clinical activities for rapid-cycle quality improvement.

Science.gov (United States)

Wofford, James Lucius; Campos, Claudia L; Jones, Robert E; Stevens, Sheila F

2015-03-12

Surveying patients is increasingly important for evaluating and improving health care delivery, but practical survey strategies during routine care activities have not been available. We examined the feasibility of conducting routine patient surveys in a primary care clinic using commercially available technology (Web-based survey creation, deployment on tablet computers, cloud-based management of survey data) to expedite and enhance several steps in data collection and management for rapid quality improvement cycles. We used a Web-based data management tool (survey creation, deployment on tablet computers, real-time data accumulation and display of survey results) to conduct four patient surveys during routine clinic sessions over a one-month period. Each survey consisted of three questions and focused on a specific patient care domain (dental care, waiting room experience, care access/continuity, Internet connectivity). Of the 727 available patients during clinic survey days, 316 patients (43.4%) attempted the survey, and 293 (40.3%) completed the survey. For the four 3-question surveys, the average time per survey was overall 40.4 seconds, with a range of 5.4 to 20.3 seconds for individual questions. Yes/No questions took less time than multiple choice questions (average 9.6 seconds versus 14.0). Average response time showed no clear pattern by order of questions or by proctor strategy, but monotonically increased with number of words in the question (30 words)-8.0, 11.8, 16.8, seconds, respectively. This technology-enabled data management system helped capture patient opinions, accelerate turnaround of survey data, with minimal impact on a busy primary care clinic. This new model of patient survey data management is feasible and sustainable in a busy office setting, supports and engages clinicians in the quality improvement process, and harmonizes with the vision of a learning health care system.

The evolution of primary progressive apraxia of speech.

Science.gov (United States)

Josephs, Keith A; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Schwarz, Christopher G; Reid, Robert I; Spychalla, Anthony J; Lowe, Val J; Jack, Clifford R; Whitwell, Jennifer L

2014-10-01

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13

An Extended Multilocus Sequence Typing (MLST Scheme for Rapid Direct Typing of Leptospira from Clinical Samples.

Directory of Open Access Journals (Sweden)

Sabrina Weiss

2016-09-01

Full Text Available Rapid typing of Leptospira is currently impaired by requiring time consuming culture of leptospires. The objective of this study was to develop an assay that provides multilocus sequence typing (MLST data direct from patient specimens while minimising costs for subsequent sequencing.An existing PCR based MLST scheme was modified by designing nested primers including anchors for facilitated subsequent sequencing. The assay was applied to various specimen types from patients diagnosed with leptospirosis between 2014 and 2015 in the United Kingdom (UK and the Lao Peoples Democratic Republic (Lao PDR. Of 44 clinical samples (23 serum, 6 whole blood, 3 buffy coat, 12 urine PCR positive for pathogenic Leptospira spp. at least one allele was amplified in 22 samples (50% and used for phylogenetic inference. Full allelic profiles were obtained from ten specimens, representing all sample types (23%. No nonspecific amplicons were observed in any of the samples. Of twelve PCR positive urine specimens three gave full allelic profiles (25% and two a partial profile. Phylogenetic analysis allowed for species assignment. The predominant species detected was L. interrogans (10/14 and 7/8 from UK and Lao PDR, respectively. All other species were detected in samples from only one country (Lao PDR: L. borgpetersenii [1/8]; UK: L. kirschneri [1/14], L. santarosai [1/14], L. weilii [2/14].Typing information of pathogenic Leptospira spp. was obtained directly from a variety of clinical samples using a modified MLST assay. This assay negates the need for time-consuming culture of Leptospira prior to typing and will be of use both in surveillance, as single alleles enable species determination, and outbreaks for the rapid identification of clusters.

Targeting ECM Disrupts Cancer Progression

DEFF Research Database (Denmark)

Venning, Freja A; Wullkopf, Lena; Erler, Janine T

2015-01-01

, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression....

Closing the gap between knowledge and clinical application: challenges for genomic translation.

Science.gov (United States)

Burke, Wylie; Korngiebel, Diane M

2015-01-01

Despite early predictions and rapid progress in research, the introduction of personal genomics into clinical practice has been slow. Several factors contribute to this translational gap between knowledge and clinical application. The evidence available to support genetic test use is often limited, and implementation of new testing programs can be challenging. In addition, the heterogeneity of genomic risk information points to the need for strategies to select and deliver the information most appropriate for particular clinical needs. Accomplishing these tasks also requires recognition that some expectations for personal genomics are unrealistic, notably expectations concerning the clinical utility of genomic risk assessment for common complex diseases. Efforts are needed to improve the body of evidence addressing clinical outcomes for genomics, apply implementation science to personal genomics, and develop realistic goals for genomic risk assessment. In addition, translational research should emphasize the broader benefits of genomic knowledge, including applications of genomic research that provide clinical benefit outside the context of personal genomic risk.

Clinical features of Parkinson's disease with and without rapid eye movement sleep behavior disorder.

Science.gov (United States)

Liu, Ye; Zhu, Xiao-Ying; Zhang, Xiao-Jin; Kuo, Sheng-Han; Ondo, William G; Wu, Yun-Cheng

2017-01-01

Rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) are two distinct clinical diseases but they share some common pathological and anatomical characteristics. This study aims to confirm the clinical features of RBD in Chinese PD patients. One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in  Department of Neurology, Shanghai General Hospital from January 2013 to August 2014. This study examined PD patients with or without RBD as determined by the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), assessed motor subtype by Unified PD Rating Scale (UPDRS) III at "on" state, and compared the sub-scale scores representing tremor, rigidity, appendicular and axial. Investigators also assessed the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Parkinson's disease Sleep Scale (PDSS). One hundred fourty one PD patients entered the final study. 30 (21.28%) PD patients had probable RBD (pRBD) diagnosed with a RBDSQ score of 6 or above. There were no significant differences for age, including age of PD onset and PD duration, gender, smoking status, alcohol or coffee use, presence of anosmia or freezing, UPDRS III, and H-Y stages between the pRBD + and pRBD - groups. pRBD + group had lower MMSE scores, higher PDSS scores, and pRBD + PD patients had more prominent proportion in anxiety, depression, constipation, hallucination and a greater prevalence of orthostatic hypotension. pRBD + PD patients exhibited greater changes in non-motor symptoms. However, there was no increase in motor deficits.

Information Loss from Technological Progress

International Nuclear Information System (INIS)

Townsend, P D

2014-01-01

Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies

Information Loss from Technological Progress

Science.gov (United States)

Townsend, P. D.

2014-12-01

Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.

Clinical diagnosis and treatment of necrotizing ulcerative gingivitis in the orthodontic patient. A case report.

Directory of Open Access Journals (Sweden)

Jesús Rodríguez-Pulido

2016-04-01

Full Text Available Introduction: About 0.1% of the population suffers from necrotizing ulcerative gingivitis, a disease of rapid progression and acute manifestation, which may progress to necrotizing ulcerative periodontitis and eventually to bone sequestration and loss of gingival tissue. Case report: A 21-year-old female patient undergoing orthodontic treatment for six months, diagnosed with necrotizing ulcerative gingivitis due to acute pain in the gingival tissue, spontaneous bleeding, halitosis and abundant plaque. The treatment was conservative and effective, obtaining total remission of the lesion after seven days and three months of postoperative follow-up. Conclusion: Today there are no epidemiological or clinical reports that support the relationship of necrotizing ulcerative gingivitis and orthodontic treatment. Prevention is critical to the success of the treatment, which is why the dentist should recognize the clinical features of necrotizing ulcerative gingivitis to raise awareness of its risks in the orthodontic patient.

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

Progression of Liver Disease

Science.gov (United States)

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Nanomaterial-enabled Rapid Detection of Water Contaminants.

Science.gov (United States)

Mao, Shun; Chang, Jingbo; Zhou, Guihua; Chen, Junhong

2015-10-28

Water contaminants, e.g., inorganic chemicals and microorganisms, are critical metrics for water quality monitoring and have significant impacts on human health and plants/organisms living in water. The scope and focus of this review is nanomaterial-based optical, electronic, and electrochemical sensors for rapid detection of water contaminants, e.g., heavy metals, anions, and bacteria. These contaminants are commonly found in different water systems. The importance of water quality monitoring and control demands significant advancement in the detection of contaminants in water because current sensing technologies for water contaminants have limitations. The advantages of nanomaterial-based sensing technologies are highlighted and recent progress on nanomaterial-based sensors for rapid water contaminant detection is discussed. An outlook for future research into this rapidly growing field is also provided. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Science.gov (United States)

Pavesio, C E; Mitchell, S M; Barton, K; Schwartz, S D; Towler, H M; Lightman, S

1995-01-01

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

Application of Next-generation Sequencing in Clinical Molecular Diagnostics

Directory of Open Access Journals (Sweden)

Morteza Seifi

2017-05-01

Full Text Available ABSTRACT Next-generation sequencing (NGS is the catch all terms that used to explain several different modern sequencing technologies which let us to sequence nucleic acids much more rapidly and cheaply than the formerly used Sanger sequencing, and as such have revolutionized the study of molecular biology and genomics with excellent resolution and accuracy. Over the past years, many academic companies and institutions have continued technological advances to expand NGS applications from research to the clinic. In this review, the performance and technical features of current NGS platforms were described. Furthermore, advances in the applying of NGS technologies towards the progress of clinical molecular diagnostics were emphasized. General advantages and disadvantages of each sequencing system are summarized and compared to guide the selection of NGS platforms for specific research aims.

Usefulness of clinical data and rapid diagnostic tests to identify bacterial etiology in adult respiratory infections

Directory of Open Access Journals (Sweden)

Pilar Toledano-Sierra

2015-01-01

Full Text Available Respiratory tract infections are a common complaint and most of them, such as common cold and laryngitis, are viral in origin, so antibiotic use should be exceptional. However, there are other respiratory tract infections (sinusitis, pharyngitis, lower respiratory tract infections, and exacerbations of chronic obstructive pulmonary disease where a bacterial etiology is responsible for a non-negligible percentage, and antibiotics are often empirically indicated. The aim of the study is to identify the strength of the data obtained from the symptoms, physical examination and rapid diagnostic methods in respiratory infections in which antibiotic use is frequently proposed in order to improve diagnosis and influence the decision to prescribe these drugs. The review concludes that history, physical examination and rapid tests are useful to guide the need for antibiotic treatment in diseases such as acute sinusitis, acute pharyngitis, exacerbation of lower respiratory tract infection and chronic obstructive pulmonary disease. However, no isolated data is accurate enough by itself to confirm or rule out the need for antibiotics. Therefore, clinical prediction rules bring together history and physical examination, thereby improving the accuracy of the decision to indicate or not antibiotics.

The Impact of Combination Therapy with a-Blockers and 5ARIs on the Progression of BPH.

Science.gov (United States)

Sountoulides, Petros; Gravas, Stavros

2015-01-01

Benign prostatic hyperplasia (BPH) can be a progressive disease for some men with significant impact on their quality of life due to worsening of symptoms, risk of acute urinary retention (AUR) and surgery. Certain clinical parameters such as age, prostate volume and PSA are able to predict those patients with BPH-associated LUTS that are at risk of disease progression. These patients will likely benefit most from medical therapy that provides symptom relief while at the same time may prevent disease progression. Studies have shown that a-blockers, although able to rapidly alleviate symptoms, have no effect on prostate volume, risk for AUR and BPH-related surgery. On the other hand 5ARIs have proven their efficacy in reducing prostate size, the risk of AUR and prostate surgery. Therefore combination therapy with an a-blocker and a 5ARI can be the mainstay of treatment for those patients at risk of BPH progression. Patients' perspective and their needs and expectations from treatment are other crucial parameters to consider in order selecting the optimal management of BPH. Therefore physicians should take into consideration the drug properties and also the patients' preferences before deciding on the optimal pharmacological treatment for BPH-associated LUTS.

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

Directory of Open Access Journals (Sweden)

Hanysova Sandra

2017-08-01

Full Text Available Objective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5 to the risk of multiple sclerosis (MS development and find out the possible association with disease disability progression rate. Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups - slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR. Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04 and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 - 0.74; p=0.006 are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 - 0.97; p=0.05. Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 - 0.98; p=0.05 and middle (OR 0.33; 95%CI 0.11 - 0.99; p=0.045. We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression. Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

Clinical and acoustical variability in hypokinetic dysarthria

International Nuclear Information System (INIS)

Metter, E.J.; Hanson, W.R.

1986-01-01

Ten male patients with parkinsonism secondary to Parkinson's disease or progressive supranuclear palsy had clinical neurological, speech, and acoustical speech evaluations. In addition, seven of the patients were evaluated by x-ray computed tomography (CT) and (F-18)-fluorodeoxyglucose (FDG) positron emission tomography (PET). Extensive variability of speech features, both clinical and acoustical, were found and seemed to be independent of the severity of any parkinsonian sign, CT, or FDG PET. In addition, little relationship existed between the variability across each measured speech feature. What appeared to be important for the appearance of abnormal acoustic measures was the degree of overall severity of the dysarthria. These observations suggest that a better understanding of hypokinetic dysarthria may result from more extensive examination of the variability between patients. Emphasizing a specific feature such as rapid speaking rate in characterizing hypokinetic dysarthria focuses on a single and inconstant finding in a complex speech pattern

[Clinical polymorphism of amyotrophic lateral sclerosis].

Science.gov (United States)

Kovrazhkina, E A; Razinskaya, O D; Gubsky, L V

To clarify clinical polymorphism of amyotrophic lateral sclerosis (ALS). The study was based on records of a hospital personalized register. Ninety-four patients, aged from 25 to 81 years, diagnosed with ALS according to El Escorial criteria were included. Electromyography and, if necessary, transcranial magnetic stimulation and magnetic-resonance tomography were used to confirm the diagnosis. Disease progression was assessed with the ARSFRS. Age at disease onset, progression rate and duration of survival of patients, rare symptoms of ALS ('extramotor'), time for palliative care (gastrostomy, non-invasive and invasive lung ventilation) and provision of the care to the patient, family history were recorded in a specially designed questionnaire. Most of the patients had sporadic ALS, only two familial cases were identified. Spinal onset ALS was found in 66.0% of the patients, bulbar onset in 29.8%, diffuse onset (spinal and bulbar motor neurons were affected simultaneously) in 4.2%. Moderate ALS progression was observed in 42.6% of the patients, mean time till death was 3.0±1.2 years. A slow progression was found in patients with cervical, low back and bulbar onset. A rapid and even 'momentary' type of progression was in diffuse and breast onset. An extremely slow progression with the long-term hospital treatment and survival >5 years was found in 9.7%. Rare ALS symptoms were represented by specific cognitive and psychological impairments, a type of frontal/temporal dysfunction, but only 5 (5.3%) patients were diagnosed with ALS-dementia. Signs of pathological muscle fatigue (myasthenic syndrome) were identified in 18 (19.1%), extrapyramidal disorders in 5 (5.3%), coordination disorders in 4 (4.3%), pain in 12 (12.8%), sensory symptoms in 5 (5.3%) of the patients. ALS is a multisystemic neurodegeneration disease though the progressive motor neuron death determines the fatal outcome.

Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events.

Science.gov (United States)

Puri, Rishi; Nissen, Steven E; Shao, Mingyuan; Elshazly, Mohamed B; Kataoka, Yu; Kapadia, Samir R; Tuzcu, E Murat; Nicholls, Stephen J

2016-11-01

Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume. Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (β=0.62; P<0.001) compared with changes in LDLC (β=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve. Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk. © 2016 American Heart Association, Inc.

Linked Clinical Trials – The Development of New Clinical Learning Studies in Parkinson’s Disease Using Screening of Multiple Prospective New Treatments

Science.gov (United States)

Brundin, Patrik; Barker, Roger A.; Conn, P. Jeffrey; Dawson, Ted M.; Kieburtz, Karl; Lees, Andrew J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Isaacs, Tom; Duffen, Joy; Matthews, Helen; Wyse, Richard K.H.

2015-01-01

Finding new therapies for Parkinson’s disease (PD) is a slow process. We assembled an international committee of experts to examine drugs potentially suitable for repurposing to modify PD progression. This committee evaluated multiple drugs currently used, or being developed, in other therapeutic areas, as well as considering several natural, non-pharmaceutical compounds. The committee prioritized which of these putative treatments were most suited to move immediately into pilot clinical trials. Aspects considered included known modes of action, safety, blood-brain-barrier penetration, preclinical data in animal models of PD and the possibility to monitor target engagement in the brain. Of the 26 potential interventions, 10 were considered worth moving forward into small, parallel ‘learning’ clinical trials in PD patients. These trials could be funded in a multitude of ways through support from industry, research grants and directed philanthropic donations. The committee-based approach to select the candidate compounds might help rapidly identify new potential PD treatment strategies for use in clinical trials. PMID:24018336

Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

Directory of Open Access Journals (Sweden)

Nae Yoon Lee

2013-03-01

Full Text Available We present the construction of the lab-on-a-chip (LOC system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane] for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level.

Rapid Clinical Bacteriology and Its Future Impact

Science.gov (United States)

Durand, Géraldine; Peyret, Michel; Chatellier, Sonia; Zambardi, Gilles; Schrenzel, Jacques; Shortridge, Dee; Engelhardt, Anette; Dunne, William Michael

2013-01-01

Clinical microbiology has always been a slowly evolving and conservative science. The sub-field of bacteriology has been and still is dominated for over a century by culture-based technologies. The integration of serological and molecular methodologies during the seventies and eighties of the previous century took place relatively slowly and in a cumbersome fashion. When nucleic acid amplification technologies became available in the early nineties, the predicted "revolution" was again slow but in the end a real paradigm shift did take place. Several of the culture-based technologies were successfully replaced by tests aimed at nucleic acid detection. More recently a second revolution occurred. Mass spectrometry was introduced and broadly accepted as a new diagnostic gold standard for microbial species identification. Apparently, the diagnostic landscape is changing, albeit slowly, and the combination of newly identified infectious etiologies and the availability of innovative technologies has now opened new avenues for modernizing clinical microbiology. However, the improvement of microbial antibiotic susceptibility testing is still lagging behind. In this review we aim to sketch the most recent developments in laboratory-based clinical bacteriology and to provide an overview of emerging novel diagnostic approaches. PMID:23301218

Factors that influence career progression among postdoctoral clinical academics: a scoping review of the literature

Science.gov (United States)

Ranieri, Veronica; Barratt, Helen; Fulop, Naomi; Rees, Geraint

2016-01-01

Background The future of academic medicine is uncertain. Concerns regarding the future availability of qualified and willing trainee clinical academics have been raised worldwide. Of significant concern is our failure to retain postdoctoral trainee clinical academics, who are likely to be our next generation of leaders in scientific discovery. Objectives To review the literature about factors that may influence postdoctoral career progression in early career clinical academics. Design This study employed a scoping review method. Three reviewers separately assessed whether the articles found fit the inclusion criteria. Data sources PubMed, Scopus, Web of Science and Google Scholar (1991–2015). Article selection The review encompassed a broad search of English language studies published anytime up to November 2015. All articles were eligible for inclusion, including research papers employing either quantitative or qualitative methods, as well as editorials and other summary articles. Data extraction Data extracted from included publications were charted according to author(s), sample population, study design, key findings, country of origin and year of publication. Results Our review identified 6 key influences: intrinsic motivation, work–life balance, inclusiveness, work environment, mentorship and availability of funding. It also detected significant gaps within the literature about these influences. Conclusions Three key steps are proposed to help support postdoctoral trainee clinical academics. These focus on ensuring that researchers feel encouraged in their workplace, involved in collaborative dialogue with key stakeholders and able to access reliable information regarding their chosen career pathway. Finally, we highlight recommendations for future research. PMID:27798036

Automated pre-processing and multivariate vibrational spectra analysis software for rapid results in clinical settings

Science.gov (United States)

Bhattacharjee, T.; Kumar, P.; Fillipe, L.

2018-02-01

Vibrational spectroscopy, especially FTIR and Raman, has shown enormous potential in disease diagnosis, especially in cancers. Their potential for detecting varied pathological conditions are regularly reported. However, to prove their applicability in clinics, large multi-center multi-national studies need to be undertaken; and these will result in enormous amount of data. A parallel effort to develop analytical methods, including user-friendly software that can quickly pre-process data and subject them to required multivariate analysis is warranted in order to obtain results in real time. This study reports a MATLAB based script that can automatically import data, preprocess spectra— interpolation, derivatives, normalization, and then carry out Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA) of the first 10 PCs; all with a single click. The software has been verified on data obtained from cell lines, animal models, and in vivo patient datasets, and gives results comparable to Minitab 16 software. The software can be used to import variety of file extensions, asc, .txt., .xls, and many others. Options to ignore noisy data, plot all possible graphs with PCA factors 1 to 5, and save loading factors, confusion matrices and other parameters are also present. The software can provide results for a dataset of 300 spectra within 0.01 s. We believe that the software will be vital not only in clinical trials using vibrational spectroscopic data, but also to obtain rapid results when these tools get translated into clinics.

Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus

Directory of Open Access Journals (Sweden)

Zong Sheng Guo

2017-12-01

Full Text Available Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome. Using this improved procedure combined with the SEM system, we have constructed multiple marker-free oncolytic poxviruses expressing different cytokines and other therapeutic genes. The high fidelity of inserted DNA sequences validates the utility of this improved procedure for generation of therapeutic viruses for human patients. We have created an oncolytic poxvirus expressing human chemokine CCL5, designated as vvDD-A34R-hCCL5, with manipulations at two genetic loci in a single virus. Finally, we have produced and purified this virus in clinical grade for its use in a phase I clinical trial and presented data on initial in vitro characterization of the virus.

Estrogens and progression of diabetic kidney damage.

Science.gov (United States)

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

2011-01-01

It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

Progressive Supranuclear Palsy: an Update.

Science.gov (United States)

Armstrong, Melissa J

2018-02-17

Progressive supranuclear palsy (PSP) is a 4R tau neuropathologic entity. While historically defined by the presence of a vertical supranuclear gaze palsy and falls in the first symptomatic year, clinicopathologic studies identify alternate presenting phenotypes. This article reviews the new PSP diagnostic criteria, diagnostic approaches, and treatment strategies. The 2017 International Parkinson and Movement Disorder Society PSP criteria outline 14 core clinical features and 4 clinical clues that combine to diagnose one of eight PSP phenotypes with probable, possible, or suggestive certainty. Evidence supports the use of select imaging approaches in the classic PSP-Richardson syndrome phenotype. Recent trials of putative disease-modifying agents showed no benefit. The new PSP diagnostic criteria incorporating the range of presenting phenotypes have important implications for diagnosis and research. More work is needed to understand how diagnostic evaluations inform phenotype assessment and identify expected progression. Current treatment is symptomatic, but tau-based therapeutics are in active clinical trials.

The clinical application of linagliptin in Asians

Directory of Open Access Journals (Sweden)

Cao CQ

2015-09-01

Full Text Available Chu-qing Cao, Yu-fei Xiang, Zhi-guang Zhou Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Asia has a growing diabetic population. Linagliptin, a member of dipeptidyl peptidase-4 inhibitor class, is unique in its nonlinear pharmacokinetics with the characteristics of rapid attainment of steady state, little accumulation, predominantly nonrenal route of elimination, prolonged terminal half-life, and sustained inhibition of dipeptidyl peptidase-4 enzyme. No clinically relevant difference in pharmacokinetics was observed between Asians and non-Asians. The management of type 2 diabetes is increasingly challenging with the progression of disease, especially with the requirements of minimal hypoglycemia, weight gain, fluid retention, and other adverse effects. Linagliptin was efficacious and well-tolerated in Asian type 2 diabetes patients with or without renal or hepatic dysfunctions, comparable to that in Caucasians. This review will focus on the usage of linagliptin in clinical studies in Asians. Keywords: linagliptin, Asians, type 2 diabetes

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

Science.gov (United States)

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

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.

Topographic changes of ictal hyperperfusion during progression of clinical seizures

Energy Technology Data Exchange (ETDEWEB)

Shin, Won Chul; Hong, Seung Bong; Tae, Woo Suk; Shon, Young Min; Seo, Dae Won; Kim, Byoung Joon; Hong, Seung Chyul; Kim, Sang Eun [School of Medicine, Sungkyunkwan, Seoul (Korea, Republic of)

2001-12-01

To investigate ictal hyperperfusion patterns during semiologic progression of seizures, we performed SPECT subtraction in 50 patients with temporal lobe epilepsy (TLE). The patients were categorized into five groups according to semiologic progression during ictal SPECT (group-1 having only aura; group-2 having motionless staring with or without aura; group-3 having motionless staring and then automatism with or without aure; group-4 having motionless staring and then automatism with or withour aura; group-4 having motionless staring and then dystonic posturing with or without aura and automatism; group-5 having motionless staring, automatism, then head version and generalized seizures with or without aura and dystonic posturing). In group-1, three patients showed ipsilateral temporal hyperperfusion and two had bilateral temporal hyperperfusion with ipsilateral predominance. In group-2, three (42.9%) patients showed bilateral temporal hyperperfusion with unilateral predominance and four (57.1%) revealed insular hyperperfusion of epileptic side. In group-3, 15 patients (88.2%) showed bilateral temporal hyperperfusion with unilateral predominance and 12 (70.6%) insular hyperperfusion. In group-4, 11 patients (84.6%) showed basal ganglia hyperperfusion on the opposite hemisphere to the side of the dystonic posturing. In group-5, there were multiple hyperperfusion areas in the frontal, temporal and basal ganglia regions. However, the injection times of radiotracer in five groups were relatively short and similar. The semiologic progression in TLE seizures were related to the propagation of hyperperfusion from ipsilateral temporal lobe to contralateral temporal lobe, insula, basal ganglia, and frontal lobe. Not only the radiotracer injection time but also semiologic progression after the injection was significant in determining hyperperfusion pattern of ictal SPECT.

Physicians’ Progress Notes

DEFF Research Database (Denmark)

Bansler, Jørgen; Havn, Erling C.; Mønsted, Troels

2013-01-01

in patient care, they have not dealt specifically with the role, structure, and content of the progress notes. As a consequence, CSCW research has not yet taken fully into account the fact that progress notes are coordinative artifacts of a rather special kind, an open-ended chain of prose texts, written...... sequentially by cooperating physicians for their own use as well as for that of their colleagues. We argue that progress notes are the core of the medical record, in that they marshal and summarize the overwhelming amount of data that is available in the modern hospital environment, and that their narrative...... format is uniquely adequate for the pivotal epistemic aspect of cooperative clinical work: the narrative format enables physicians to not only record ‘facts’ but also—by filtering, interpreting, organizing, and qualifying information—to make sense and act concertedly under conditions of uncertainty...

Clinical predictors for the prognosis of myasthenia gravis.

Science.gov (United States)

Wang, Lili; Zhang, Yun; He, Maolin

2017-04-19

Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.

Helical Tomotherapy-Based STAT RT: Dosimetric Evaluation for Clinical Implementation of a Rapid Radiation Palliation Program

International Nuclear Information System (INIS)

McIntosh, Alyson; Dunlap, Neal; Sheng, Ke; Geezey, Constance; Turner, Benton; Blackhall, Leslie; Weiss, Geoffrey; Lappinen, Eric; Larner, James M.; Read, Paul W.

2010-01-01

Helical tomotherapy-based STAT radiation therapy (RT) uses an efficient software algorithm for rapid intensity-modulated treatment planning, enabling conformal radiation treatment plans to be generated on megavoltage computed tomography (MVCT) scans for CT simulation, treatment planning, and treatment delivery in one session. We compared helical tomotherapy-based STAT RT dosimetry with standard linac-based 3D conformal plans and standard helical tomotherapy-based intensity-modulated radiation therapy (IMRT) dosimetry for palliative treatments of whole brain, a central obstructive lung mass, multilevel spine disease, and a hip metastasis. Specifically, we compared the conformality, homogeneity, and dose with regional organs at risk (OARs) for each plan as an initial step in the clinical implementation of a STAT RT rapid radiation palliation program. Hypothetical planning target volumes (PTVs) were contoured on an anthropomorphic phantom in the lung, spine, brain, and hip. Treatment plans were created using three planning techniques: 3D conformal on Pinnacle 3 , helical tomotherapy, and helical tomotherapy-based STAT RT. Plan homogeneity, conformality, and dose to OARs were analyzed and compared. STAT RT and tomotherapy improved conformality indices for spine and lung plans (CI spine = 1.21, 1.17; CI lung = 1.20, 1.07, respectively) in comparison with standard palliative anteroposterior/posteroanterior (AP/PA) treatment plans (CI spine = 7.01, CI lung = 7.30), with better sparing of heart, esophagus, and spinal cord. For palliative whole-brain radiotherapy, STAT RT and tomotherapy reduced maximum and mean doses to the orbits and lens (maximum/mean lens dose: STAT RT = 2.94/2.65 Gy, tomotherapy = 3.13/2.80 Gy, Lateral opposed fields = 7.02/3.65 Gy), with an increased dose to the scalp (mean scalp dose: STAT RT = 16.19 Gy, tomotherapy = 15.61 Gy, lateral opposed fields = 14.01 Gy). For bony metastatic hip lesions, conformality with both tomotherapy techniques (CI = 1

Fungal Infections of the Central Nervous System in Small Animals: Clinical Features, Diagnosis, and Management.

Science.gov (United States)

Bentley, R Timothy; Taylor, Amanda R; Thomovsky, Stephanie A

2018-01-01

Small animal mycoses vary geographically. Different clinical presentations are seen in animals with infection of the central nervous system (CNS), including multifocal meningoencephalomyelitis, intracranial lesions that accompany sinonasal lesions, rapidly progressive ventriculitis, or solitary granuloma of the brain or spinal cord. Systemic, nasal, or extraneural clinical signs are common but, especially in granuloma cases, do not always occur. Surgery may have a diagnostic and therapeutic role in CNS granuloma. There have been recent advancements in serology. Fluconazole, voriconazole, and posaconazole cross the blood-brain barrier, but voriconazole is neurotoxic to cats. Liposomal and lipid-encapsulated formulations of amphotericin B are preferred. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistence, spatial distribution and implications for progression detection of blind parts of the visual field in glaucoma: a clinical cohort study.

Directory of Open Access Journals (Sweden)

Francisco G Junoy Montolio

Full Text Available BACKGROUND: Visual field testing is an essential part of glaucoma care. It is hampered by variability related to the disease itself, response errors and fatigue. In glaucoma, blind parts of the visual field contribute to the diagnosis but--once established--not to progression detection; they only increase testing time. The aims of this study were to describe the persistence and spatial distribution of blind test locations in standard automated perimetry in glaucoma and to explore how the omission of presumed blind test locations would affect progression detection. METHODOLOGY/PRINCIPAL FINDINGS: Data from 221 eyes of 221 patients from a cohort study with the Humphrey Field Analyzer with 30-2 grid were used. Patients were stratified according to baseline mean deviation (MD in six strata of 5 dB width each. For one, two, three and four consecutive 0.1 for all strata. Omitting test locations with three consecutive <0 dB sensitivities at baseline did not affect the performance of the MD-based Nonparametric Progression Analysis progression detection algorithm. CONCLUSIONS/SIGNIFICANCE: Test locations that have been shown to be reproducibly blind tend to display a reasonable blindness persistence and do no longer contribute to progression detection. There is no clinically useful universal MD cut-off value beyond which testing can be limited to 10 degree eccentricity.

Early detection of emphysema progression

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin

2010-01-01

Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

Pediatric nasopharyngeal carcinoma: Anatomo-clinic aspects, therapeutic results and progressive particularities

International Nuclear Information System (INIS)

Frikha, M.; Toumi, N.; Ghorbel, L.; Ben Salah, H.; Daoud, J.; Khabir, A.; Boudawara, T.; Karray, H.; Gargouri, R.; Ghorbel, A.

2010-01-01

Purpose We retrospectively analyzed anatomo-clinic, therapeutic and progressive particularities of 74 young patients (= 20 years) with nasopharyngeal carcinoma treated between 1993 and 2005. Patients and methods Initial work-up included a fiberoptic naso-fiberscopy with biopsy, computed tomography and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radio chemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas. Results The median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders. Comments Pediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results. (authors)

Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

Directory of Open Access Journals (Sweden)

HAN Shun-chang

2013-04-01

Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review of Literature.

Science.gov (United States)

Torabi, Kianoosh; Farjood, Ehsan; Hamedani, Shahram

2015-03-01

The early computer-aided design/computer-aided manufacturing (CAD/CAM) systems were relied exclusively on subtractive methods. In recent years, additive methods by employing rapid prototyping (RP) have progressed rapidly in various fields of dentistry as they have the potential to overcome known drawbacks of subtractive techniques such as fit problems. RP techniques have been exploited to build complex 3D models in medicine since the 1990s. RP has recently proposed successful applications in various dental fields, such as fabrication of implant surgical guides, frameworks for fixed and removable partial dentures, wax patterns for the dental prosthesis, zirconia prosthesis and molds for metal castings, and maxillofacial prosthesis and finally, complete dentures. This paper aimed to offer a comprehensive literature review of various RP methods, particularly in dentistry, that are expected to bring many improvements to the field. A search was made through MEDLINE database and Google scholar search engine. The keywords; 'rapid prototyping' and 'dentistry' were searched in title/abstract of publications; limited to 2003 to 2013, concerning past decade. The inclusion criterion was the technical researches that predominately included laboratory procedures. The exclusion criterion was meticulous clinical and excessive technical procedures. A total of 106 articles were retrieved, recited by authors and only 50 met the specified inclusion criteria for this review. Selected articles had used rapid prototyping techniques in various fields in dentistry through different techniques. This review depicted the different laboratory procedures employed in this method and confirmed that RP technique have been substantially feasible in dentistry. With advancement in various RP systems, it is possible to benefit from this technique in different dental practices, particularly in implementing dental prostheses for different applications.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models.

Science.gov (United States)

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-09-01

To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. © 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

Factors that influence career progression among postdoctoral clinical academics: a scoping review of the literature.

Science.gov (United States)

Ranieri, Veronica; Barratt, Helen; Fulop, Naomi; Rees, Geraint

2016-10-21

The future of academic medicine is uncertain. Concerns regarding the future availability of qualified and willing trainee clinical academics have been raised worldwide. Of significant concern is our failure to retain postdoctoral trainee clinical academics, who are likely to be our next generation of leaders in scientific discovery. To review the literature about factors that may influence postdoctoral career progression in early career clinical academics. This study employed a scoping review method. Three reviewers separately assessed whether the articles found fit the inclusion criteria. PubMed, Scopus, Web of Science and Google Scholar (1991-2015). The review encompassed a broad search of English language studies published anytime up to November 2015. All articles were eligible for inclusion, including research papers employing either quantitative or qualitative methods, as well as editorials and other summary articles. Data extracted from included publications were charted according to author(s), sample population, study design, key findings, country of origin and year of publication. Our review identified 6 key influences: intrinsic motivation, work-life balance, inclusiveness, work environment, mentorship and availability of funding. It also detected significant gaps within the literature about these influences. Three key steps are proposed to help support postdoctoral trainee clinical academics. These focus on ensuring that researchers feel encouraged in their workplace, involved in collaborative dialogue with key stakeholders and able to access reliable information regarding their chosen career pathway. Finally, we highlight recommendations for future research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

Science.gov (United States)

Sasai-Sakuma, Taeko; Frauscher, Birgit; Mitterling, Thomas; Ehrmann, Laura; Gabelia, David; Brandauer, Elisabeth; Inoue, Yuichi; Poewe, Werner; Högl, Birgit

2014-09-01

Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical and electroretinographic findings of progressive retinal atrophy in miniature schnauzer dogs of South Korea.

Science.gov (United States)

Jeong, Man Bok; Park, Shin Ae; Kim, Se Eun; Park, Young Woo; Narfström, Kristina; Seo, Kangmoon

2013-10-01

The purpose of the study was to describe the clinical and electroretinographic features of clinical cases of progressive retinal atrophy (PRA) in miniature schnauzer (MS) of South Korea. Sixty-six MS (14 normal and 52 affected) were included. All animals underwent routine ocular examinations. Electroretinogram (ERG) was recorded in the 14 normal and 15 affected dogs. For normal dogs, the mean age ± SD was 4.1 ± 2.4 years (1 to 9 years), and there were no ocular abnormalities on the basis of ocular examinations and ERG results. For the PRA-affected dogs, it was shown that the mean age ± SD was 4.3 ± 1.1 years (2 to 7 years), and 44 dogs (84.6%) were 3 to 5 years old. Most of the PRA-affected dogs had abnormal menace responses (98.1%) and pupillary light reflexes (PLRs, 88.5%); some dogs showed normal menace response (1.9%) and PLRs (11.5%). Ophthalmoscopic abnormalities in the affected group included one or more of the following changes: hyperreflectivity and discoloration of the tapetal area, attenuation of retinal vessels, depigmentation in non-tapetal area and optic disc atrophy. ERG in the affected dogs showed non-recordable responses in all cases tested with clinical signs of PRA. The present study showed that PRA in MS was mainly observed between the age of 3 to 5 years. ERG revealed abnormal rod and cone responses in affected dogs at the ages studied.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

Science.gov (United States)

Molnar, Christoph; Scherer, Almut; Baraliakos, Xenofon; de Hooge, Manouk; Micheroli, Raphael; Exer, Pascale; Kissling, Rudolf O; Tamborrini, Giorgio; Wildi, Lukas M; Nissen, Michael J; Zufferey, Pascal; Bernhard, Jürg; Weber, Ulrich; Landewé, Robert B M; van der Heijde, Désirée; Ciurea, Adrian

2018-01-01

To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Rapid learning: a breakthrough agenda.

Science.gov (United States)

Etheredge, Lynn M

2014-07-01

A "rapid-learning health system" was proposed in a 2007 thematic issue of Health Affairs. The system was envisioned as one that uses evidence-based medicine to quickly determine the best possible treatments for patients. It does so by drawing on electronic health records and the power of big data to access large volumes of information from a variety of sources at high speed. The foundation for a rapid-learning health system was laid during 2007-13 by workshops, policy papers, large public investments in databases and research programs, and developing learning systems. Challenges now include implementing a new clinical research system with several hundred million patients, modernizing clinical trials and registries, devising and funding research on national priorities, and analyzing genetic and other factors that influence diseases and responses to treatment. Next steps also should aim to improve comparative effectiveness research; build on investments in health information technology to standardize handling of genetic information and support information exchange through apps and software modules; and develop new tools, data, and information for clinical decision support. Further advances will require commitment, leadership, and public-private and global collaboration. Project HOPE—The People-to-People Health Foundation, Inc.

Opioid detoxification : from controlled clinical trial to clinical practice

NARCIS (Netherlands)

Dijkstra, Boukje A G; De Jong, Cor A J; Wensing, Michel; Krabbe, Paul F M; van der Staak, Cees P F

2010-01-01

Controlled clinical trials have high internal validity but suffer from difficulties in external validity. This study evaluates the generalizability of the results of a controlled clinical trial on rapid detoxification in the everyday clinical practice of two addiction treatment centers. The results

Progress of artificial pancreas devices towards clinical use: the first outpatient studies.

Science.gov (United States)

Russell, Steven J

2015-04-01

This article describes recent progress in the automated control of glycemia in type 1 diabetes with artificial pancreas devices that combine continuous glucose monitoring with automated decision-making and insulin delivery. After a gestation period of closely supervised feasibility studies in research centers, the last 2 years have seen publication of studies testing these devices in outpatient environments, and many more such studies are ongoing. The most basic form of automation, suspension of insulin delivery for actual or predicted hypoglycemia, has been shown to be effective and well tolerated, and a first-generation device has actually reached the market. Artificial pancreas devices that actively dose insulin fall into two categories, those that dose insulin alone and those that also use glucagon to prevent and treat hypoglycemia (bihormonal artificial pancreas). Initial outpatient clinical trials have shown that both strategies can improve glycemic management in comparison with patient-controlled insulin pump therapy, but only the bihormonal strategy has been tested without restrictions on exercise. Artificial pancreas technology has the potential to reduce acute and chronic complications of diabetes and mitigate the burden of diabetes self-management. Successful outpatient studies bring these technologies one step closer to availability for patients.

Progressive supranuclear palsy syndrome induced by clebopride.

Science.gov (United States)

Campdelacreu, Jaume; Kumru, Hatice; Tolosa, Eduard; Valls-Solé, Josep; Benabarre, Antoni

2004-04-01

We report on a patient who presented with a progressive supranuclear palsy (PSP) syndrome while receiving clebopride (CLB), a prokinetic drug with central antidopaminergic properties. The clinical and neurophysiological signs progressively disappeared after CLB withdrawal. To our knowledge, this is the first published PSP-like syndrome attributable to an antidopaminergic drug. Copyright 2003 Movement Disorder Society

Nondestructive Evaluation Program: Progress in 1986

International Nuclear Information System (INIS)

1987-07-01

The increasing cost of equipment for power generating plants and the potential increases in productivity and safety available through rapidly developing Nondestructive Evaluation (NDE) technology led EPRI to initiate a Nondestructive Evaluation Program in 1974. To date, the major focus has been on light water reactor inspection problems; however, increased application to other systems is now under way. This report presents a comprehensive review of the EPRI effort in the NDE area. Most of the report consists of contractor-supplied progress reports on each current project. An organizational plan of the program is presented in overview. In addition, organization from several viewpoints is presented, e.g., in-service inspection operators, R and D personnel, and utility representatives. The report summarizes significant progress made since the previous EPRI Special Report NP-4315-SR was issued in May 1986. Section 1 contains information about the program organization, and the sections that follow contain contractor-supplied progress reports of each current project. The progress reports are grouped by plant components - pipe, pressure vessel, steam generator and boiler tubes, and turbine. In addition, Part 6 is devoted to discussions of technology transfer

Central Blood Pressure and Chronic Kidney Disease Progression

Directory of Open Access Journals (Sweden)

Debbie L. Cohen

2011-01-01

Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

Evaluating the use of dedicated swab for rapid antigen detection ...

African Journals Online (AJOL)

Evaluating the use of dedicated swab for rapid antigen detection testing in group a ... African Journal of Clinical and Experimental Microbiology ... Several generations of rapid antigen detection tests (RADTs) have been developed to facilitate ...

Frontotemporal dementia and primary progressive aphasia, a review

Directory of Open Access Journals (Sweden)

Kirshner HS

2014-06-01

Full Text Available Howard S KirshnerDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USAAbstract: Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a neurodegenerative disease. Over time, some patients develop a more generalized dementia. Four clinical subtypes characterize the predominant presentations of this illness: behavioral or frontal variant FTD, progressive nonfluent aphasia, semantic dementia, and logopenic primary progressive aphasia. These clinical variants correlate with regional patterns of atrophy on brain imaging studies such as MRI and PET scanning, as well as with biochemical and molecular genetic variants of the disorder. The treatment is as yet only symptomatic, but advances in molecular genetics promise new therapies.Keywords: FTD, behavior variant or frontal variant FTD, pick's disease, PPA, progressive nonfluent aphasia

Rapid chemical separations

CERN Document Server

Trautmann, N

1976-01-01

A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

Using dreams to assess clinical change during treatment.

Science.gov (United States)

Glucksman, Myron L; Kramer, Milton

2004-01-01

This article describes several studies that examine the relationship between the manifest content of selected dreams reported by patients and their clinical progress during psychoanalytic and psychodynamically oriented treatment. There are a number of elements that dreaming and psychotherapy have in common: affect regulation; conflict resolution; problem-solving; self-awareness; mastery and adaptation. Four different studies examined the relationship between the manifest content of selected dreams and clinical progress during treatment. In each study, the ratings of manifest content and clinical progress by independent observers were rank-ordered and compared. In three of the four studies there was a significant correlation between the rankings of manifest content and the rankings of clinical progress. This finding suggests that the manifest content of dreams can be used as an independent variable to assess clinical progress during psychoanalytic and psychodynamically oriented treatment.

Defining active progressive multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

2017-01-01

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

Population Characteristics and Progressive Disability in Neurofibromatosis Type 2.

Science.gov (United States)

Iwatate, Kensho; Yokoo, Takeshi; Iwatate, Eriko; Ichikawa, Masahiro; Sato, Taku; Fujii, Masazumi; Sakuma, Jun; Saito, Kiyoshi

2017-10-01

To characterize the clinical features of patients with neurofibromatosis type 2 (NF2) and determine prognostic risk factors for progressive disabilities. In this retrospective cohort study of the Japanese national NF2 registry between 2009 and 2013, clinical data (demographic, history, oncologic, and neurologic) of 807 patients with a diagnosis of NF2 were analyzed. The overall severity of neurologic disability was assessed using a comprehensive 25-point scoring system encompassing a wide variety of neurologic deficits. In 587 patients in whom longitudinal disability data were available, multivariate logistic regression was performed to identify risk factors for significant progression of disability. The clinical characteristics of the Japanese NF2 population were heterogeneous. The median age of onset was 24 years (range, 1-80 years), the male:female ratio was 1:1.29, and the initial severity score was 4 (range, 0-22) out of 25 points. A family history of NF2 was present in 33% of the patients. Most frequent clinical features were bilateral cranial nerve VIII nerve sheath tumor (NST) in 87%, spinal NST in 80%, hearing loss in 65%, spinal dysfunction in 50%, intracranial meningioma in 49%, and facial paresis in 36%. The disability score progressed by ≥5 points in 6.1% of patients over the study period. Based on multivariate logistic regression analyses, the significant independent risk factors of progression (P value) included age of onset history (P = 0.007), positive treatment history (P = 0.026), hearing loss (P = 0.014), facial paresis (P = 0.015), blindness (P = 0.011), and hemiparesis (P = 0.025). The Japanese NF2 population has heterogeneous clinical features. Risk factors for progressive disability include younger age of onset, positive family history, positive treatment history, and specific neurologic deficits. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[The optimization of a surgical intervention to stabilize progressive myopia].

Science.gov (United States)

Gonchar, P A; Dushin, N V; Beliaev, V S; Kravchinina, V V; Barashkov, V I; Frolov, M A

1999-01-01

Results of 236 sclera-fortifying surgeries are followed up for more than 25 years. Progressive myopia stabilized in 95.8% cases after bandaging scleroplasty and in 87.03% cases after chondroplasty. Clinical refraction and posteroanterior axis of the eye did not increase after surgery; visual functions stabilized, and brightness sensitivity threshold was lowered. The technique of operation and clinical course of the postoperative period are described. Based on analysis of the clinical material, the authors propose the optimal approach to scleroplastic operations aimed at stabilization of progressive myopia.

Clinical features and radiological findings of adenovirus pneumonia associated with progression to acute respiratory distress syndrome: A single center study in 19 adult patients

Energy Technology Data Exchange (ETDEWEB)

Cha, Min Jae; Chong, Semin [Dept. of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul (Korea, Republic of); Chung, Myung Jin; Lee, Kyung Soo; KIm, Tae Jung; Kim, Tae Sung; Han, Jung Ho [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2016-11-15

To describe radiologic findings of adenovirus pneumonia and to understand clinico-radiological features associated with progression to acute respiratory distress syndrome (ARDS) in patients with adenovirus pneumonia. This study included 19 patients diagnosed with adenovirus pneumonia at a tertiary referral center, in the period between March 2003 and April 2015. Clinical findings were reviewed, and two radiologists assessed imaging findings by consensus. Chi-square, Fisher's exact, and Student's t tests were used for comparing patients with and without subsequent development of ARDS. Of 19 patients, nine were immunocompromised, and 10 were immunocompetent. Twelve patients (63%) progressed to ARDS, six of whom (32%) eventually died from the disease. The average time for progression to ARDS from symptom onset was 9.6 days. Initial chest radiographic findings were normal (n = 2), focal opacity (n = 9), or multifocal or diffuse opacity (n = 8). Computed tomography (CT) findings included bilateral (n = 17) or unilateral (n = 2) ground-glass opacity with consolidation (n = 14) or pleural effusion (n = 11). Patients having subsequent ARDS had a higher probability of pleural effusion and a higher total CT extent compared with the non-ARDS group (p = 0.010 and 0.007, respectively). However, there were no significant differences in clinical variables such as patient age and premorbid condition. Adenovirus pneumonia demonstrates high rates of ARDS and mortality, regardless of patient age and premorbid conditions, in the tertiary care setting. Large disease extent and presence of pleural effusion on CT are factors suggestive of progression to ARDS.

Predictors of disease progression in HIV infection: a review

Directory of Open Access Journals (Sweden)

Ananworanich Jintanat

2007-05-01

Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal.

Directory of Open Access Journals (Sweden)

Epco Hasker

Full Text Available Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers.We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified.We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers.There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies.

Clinical course of acute atrial fibrillation treated with rapid digitalization.

Science.gov (United States)

Weiner, P; Bassan, M M; Jarchovsky, J; Iusim, S; Plavnick, L

1983-02-01

Forty-seven episodes of acute atrial fibrillation (AF) in 45 patients were examined prospectively to determine the course of the disorder treated with rapid digitalization. Patients received 1.5 mg of digoxin intravenously over 12 hours. In 40 of the 47 attacks, reversion to sinus rhythm occurred with no additional therapy at 1 to 96 hours (median 4 hours) after beginning digoxin. In thirty-two patients, conversion occurred within 8 hours; only one patient showed important ventricular slowing before conversion. Thus, if digoxin facilitates conversion, it does not do so by slowing the ventricular response. Of the 11 patients still in AF at 16 hours, conversion subsequently occurred in only four who were receiving digoxin alone. We conclude that the prognosis for quick reversion to sinus rhythm in patients with acute AF treated with rapid digitalization alone is excellent. If reversion does not occur by 16 to 24 hours, additional measures to restore sinus rhythm are indicated.

Progress in research on Tourette syndrome

Science.gov (United States)

Black, Kevin J.; Jankovic, Joseph; Hershey, Tamara; McNaught, Kevin St. P.; Mink, Jonathan W.; Walkup, John

2014-01-01

Tourette syndrome (TS) is a heritable neuropsychiatric disorder commonly complicated by obsessions and compulsions, but defined by frequent unwanted movements (motor tics) and vocalizations (phonic tics) that develop in childhood or adolescence. In recent years, research on TS has progressed rapidly on several fronts. Inspired by the Fifth International Scientific Symposium on Tourette Syndrome, the articles in this special issue review advances in the phenomenology, epidemiology, genetics, pathophysiology, and treatment of TS. PMID:25436182

Progress in molecular precursors for electronic materials

Energy Technology Data Exchange (ETDEWEB)

Buhro, W.E. [Washington Univ., St. Louis, MO (United States)

1996-09-01

Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

Redistribution of hematoma to spinal subdural space as a mechanism for the rapid spontaneous resolution of posttraumatic intracranial acute subdural hematoma: case report.

Science.gov (United States)

Wong, Sui To; Yuen, Ming Keung; Fok, Kam Fuk; Yuen, Shing Chau; Yam, Kwong Yui; Fong, Dawson

2009-01-01

Rapid spontaneous resolution of posttraumatic intracranial ASDH has been reported in the literature since 1986. We report a case to demonstrate that redistribution of hematoma to the spinal subdural space is a mechanism for the rapid spontaneous resolution of posttraumatic intracranial ASDH. A 73-year-old woman with a slipped-and-fell injury had a worst GCS score of 8/15. Computerized tomography of the brain demonstrated a large intracranial ASDH with mass effect. Conservative management was decided because of her poor premorbid general condition. Rapid clinical improvement was observed within 5 hours after the CT. Progress CT of the brain at 45 hours postinjury showed that the size of the intracranial ASDH was markedly diminished. The CT findings apparently demonstrated a caudal distribution of the intracranial ASDH over the tentorium and then into the posterior fossa. To investigate this further, an MRI of the spine was performed, which showed that there was spinal SDH in the cervical and thoracic spine. This is the first report demonstrating that redistribution of posttraumatic intracranial ASDH to the spinal subdural space is one of the mechanisms behind the rapid spontaneous resolution of posttraumatic intracranial ASDH in the acute phase.

Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting

Science.gov (United States)

Patel, Vinod B.; Singh, Ravesh; Connolly, Cathy; Kasprowicz, Victoria; Zumla, Allimudin; Ndungu, Thumbi; Dheda, Keertan

2010-01-01

Background/Objective The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). Methods Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. Results Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). Conclusions Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression. PMID:21203513

Stem cells: progressions and applications in clinical medicine

Directory of Open Access Journals (Sweden)

Ali Hosseini Bereshneh

2016-05-01

of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

Directory of Open Access Journals (Sweden)

Claire Jackson

2013-01-01

Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

CERN Multimedia

1969-01-01

Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia.

Science.gov (United States)

Butler, Tom; Gribben, J G

2010-05-01

CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a "watch and wait" approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently "high-risk" that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question. Copyright 2010 Elsevier Ltd. All rights reserved.

Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review of Literature

Science.gov (United States)

Torabi, Kianoosh; Farjood, Ehsan; Hamedani, Shahram

2015-01-01

The early computer-aided design/computer-aided manufacturing (CAD/CAM) systems were relied exclusively on subtractive methods. In recent years, additive methods by employing rapid prototyping (RP) have progressed rapidly in various fields of dentistry as they have the potential to overcome known drawbacks of subtractive techniques such as fit problems. RP techniques have been exploited to build complex 3D models in medicine since the 1990s. RP has recently proposed successful applications in various dental fields, such as fabrication of implant surgical guides, frameworks for fixed and removable partial dentures, wax patterns for the dental prosthesis, zirconia prosthesis and molds for metal castings, and maxillofacial prosthesis and finally, complete dentures. This paper aimed to offer a comprehensive literature review of various RP methods, particularly in dentistry, that are expected to bring many improvements to the field. A search was made through MEDLINE database and Google scholar search engine. The keywords; ‘rapid prototyping’ and ‘dentistry’ were searched in title/abstract of publications; limited to 2003 to 2013, concerning past decade. The inclusion criterion was the technical researches that predominately included laboratory procedures. The exclusion criterion was meticulous clinical and excessive technical procedures. A total of 106 articles were retrieved, recited by authors and only 50 met the specified inclusion criteria for this review. Selected articles had used rapid prototyping techniques in various fields in dentistry through different techniques. This review depicted the different laboratory procedures employed in this method and confirmed that RP technique have been substantially feasible in dentistry. With advancement in various RP systems, it is possible to benefit from this technique in different dental practices, particularly in implementing dental prostheses for different applications. PMID:25759851

Breastfeeding progression in preterm infants is influenced by factors in infants, mothers and clinical practice

DEFF Research Database (Denmark)

Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne

2014-01-01

. Infants that were small for gestational age were associated with 5.6 days (95% CI 4.1-7.0) later establishment of exclusive breastfeeding. CONCLUSION: Breastfeeding competence is not developed at a fixed PMA, but is influenced by multiple factors in infants, mothers and clinical practice. Admitting......BACKGROUND AND AIM: Many preterm infants are not capable of exclusive breastfeeding from birth. To guide mothers in breastfeeding, it is important to know when preterm infants can initiate breastfeeding and progress. The aim was to analyse postmenstrual age (PMA) at breastfeeding milestones...... in different preterm gestational age (GA) groups, to describe rates of breastfeeding duration at pre-defined times, as well as analyse factors associated with PMA at the establishment of exclusive breastfeeding. METHODS: The study was part of a prospective survey of a national Danish cohort of preterm infants...

Spinal Dural Arteriovenous Fistula (SDAVF in a Patient with Progressive Paraparesia: A Case Report

Directory of Open Access Journals (Sweden)

Mehrdokht Mazdeh

2016-07-01

Full Text Available Background: Spinal dural arteriovenous fistula (SDAVF is a known cause of nontraumatic slow progressive araparesia and is frequently overlooked because its clinical features overlap with more common causes of myelopathy and also neuroimaging may be normal. Case Report: A 53 year-old man with developed weakness of both lower limbs had symptoms begun spontaneously 3.5 month before admission and progressed from 1 month ago with bowel and bladder incontinence. The patient's physical examination was normal and neurologic testing revealed lower extremity motor strength of 3/5. Deep tendon reflexes were decreased and superficial abdominal reflexes were absent. Sensation of pinprick and temperature was absent distal to the T4-T5 level. Vibration and proprioception were decreased to the ankle and saddle anesthesia and the patient was non ambulatory. Laboratory routine and specific tests for vitamin B12 level, hepatitis, HIV, HTLV1, 2 were negative. MRI of spine with and without contrast raised the possibility of dural arteriovenous malformation extended from T3 level to conus medullaris which was confirmed by angiography. The patient referred to neurosurgeon for deciding route of treatment. Conclusion: SDAVF can be a significant non traumatic slowly progressive cause of myelopathy. The majority of the affected patients are males older than 50 years of age. Rapid diagnosis in these patients leads to significant improvement.

Rapid Spontaneously Resolving Acute Subdural Hematoma

Science.gov (United States)

Gan, Qi; Zhao, Hexiang; Zhang, Hanmei; You, Chao

2017-01-01

Introduction: This study reports a rare patient of a rapid spontaneously resolving acute subdural hematoma. In addition, an analysis of potential clues for the phenomenon is presented with a review of the literature. Patient Presentation: A 1-year-and-2-month-old boy fell from a height of approximately 2 m. The patient was in a superficial coma with a Glasgow Coma Scale of 8 when he was transferred to the authors’ hospital. Computed tomography revealed the presence of an acute subdural hematoma with a midline shift beyond 1 cm. His guardians refused invasive interventions and chose conservative treatment. Repeat imaging after 15 hours showed the evident resolution of the hematoma and midline reversion. Progressive magnetic resonance imaging demonstrated the complete resolution of the hematoma, without redistribution to a remote site. Conclusions: Even though this phenomenon has a low incidence, the probability of a rapid spontaneously resolving acute subdural hematoma should be considered when patients present with the following characteristics: children or elderly individuals suffering from mild to moderate head trauma; stable or rapidly recovered consciousness; and simple acute subdural hematoma with a moderate thickness and a particularly low-density band in computed tomography scans. PMID:28468224

Progressive pseudorheumatoid dysplasia

International Nuclear Information System (INIS)

Mampaey, S.; De Schepper, A.; Vanhoenacker, F.; Boven, K.; Hul, W. van

2000-01-01

A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine. (orig.)

Cerebral amyloid angiopathy-related inflammation: imaging findings and clinical outcome

Energy Technology Data Exchange (ETDEWEB)

Martucci, Matia [Vall d' Hebron University Hospital, Neuroradiology Unit, Radiology Department (IDI), Barcelona (Spain); Catholic University of Sacred Heart, ' ' A. Gemelli' ' University Hospital, Department of Radiological Sciences, Rome (Italy); Sarria, Silvana; Coscojuela, Pilar; Vert, Carla; Siurana, Sahyly; Auger, Cristina; Rovira, Alex [Vall d' Hebron University Hospital, Neuroradiology Unit, Radiology Department (IDI), Barcelona (Spain); Toledo, Manuel [Vall d' Hebron University Hospital, Epilepsy Unit, Neurology Department, Barcelona (Spain)

2014-04-15

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical-subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment. (orig.)

Cerebral amyloid angiopathy-related inflammation: imaging findings and clinical outcome

International Nuclear Information System (INIS)

Martucci, Matia; Sarria, Silvana; Coscojuela, Pilar; Vert, Carla; Siurana, Sahyly; Auger, Cristina; Rovira, Alex; Toledo, Manuel

2014-01-01

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical-subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment. (orig.)

Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

Science.gov (United States)

Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

2013-05-01

Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

Science.gov (United States)

Wall, Kristin M; Rida, Wasima; Haddad, Lisa B; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H; Latka, Mary H; Anzala, Omu; Sanders, Eduard J; Bekker, Linda-Gail; Edward, Vinodh A; Price, Matt A

2017-03-01

Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement pregnancy. Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

[Riboflavin UVA crosslinking in progressive keratoconus].

Science.gov (United States)

Maier, P; Reinhard, T

2017-06-01

In patients with keratoconus, a progressive, ectatic disease of the cornea, the shape of the cornea is continuously changing leading to a reduction in visual acuity by progressive myopia and more and more (irregular) astigmatism. The symptomatic treatment consists of the prescription of glasses or special gas-permeable rigid contact lenses. Corneal tomography is generally used for diagnosis. After initial diagnosis of keratoconus, regular tomographic follow-ups should be performed. If clinically significant progression is found and confirmed by repeated measurements, riboflavin UVA collagen crosslinking should be offered to the patients. The aim of riboflavin UVA collagen crosslinking is to halt the progression of the disease to avoid further complications. The therapeutic principle is a combined effect of the photosensitizer riboflavin and UVA light. This stiffening effect of the corneal tissue halts the progression of keratoconus. The efficacy of this treatment has been demonstrated in various randomized, controlled trials.

SCN8A encephalopathy: Research progress and prospects.

Science.gov (United States)

Meisler, Miriam H; Helman, Guy; Hammer, Michael F; Fureman, Brandy E; Gaillard, William D; Goldin, Alan L; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L; Lossin, Christoph; Mefford, Heather C; Parent, Jack M; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L; Vanderver, Adeline; Scheffer, Ingrid E

2016-07-01

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations

Directory of Open Access Journals (Sweden)

Savita Nandal

2017-02-01

Full Text Available Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management).

Science.gov (United States)

Little, Paul; Hobbs, F D Richard; Moore, Michael; Mant, David; Williamson, Ian; McNulty, Cliodna; Cheng, Ying Edith; Leydon, Geraldine; McManus, Richard; Kelly, Joanne; Barnett, Jane; Glasziou, Paul; Mullee, Mark

2013-10-10

To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. Open adaptive pragmatic parallel group randomised controlled trial. Primary care in United Kingdom. Patients aged ≥ 3 with acute sore throat. An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (-0.33, 95% confidence interval -0.64 to -0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (-0.30, -0.61 to -0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval 0.50 to 0.95; P=0.02) and in the

Exclusion and diagnosis of pulmonary embolism by a rapid ELISA D-dimer test and noninvasive imaging techniques within the context of a clinical model.

Science.gov (United States)

Michiels, J J; Pattynama, P M

2000-01-01

A negative rapid ELISA D-dimer test alone in out-patients with a low to moderate clinical probability (CP) on pulmonary embolism (PE) is predicted to safely exclude pulmonary embolism. The combination of a negative rapid ELISA D-dimer test and a low to moderate CP on PE followed by compression ultrasonography (CUS) for the detection of deep vein thrombosis (DVT) is safe and cost-effective as it reduces the need for noninvasive imaging techniques to about 50% to 60% of outpatients with suspected PE. A high probability ventilation-perfusion (VP) scan or a positive spiral CT consistent with PE and the detection of DVT by CUS are currently considered to be clear indications for anticoagulant treatment. Subsequent pulmonary angiography (PA) is the gold standard diagnostic strategy to exclude or diagnose PE in suspected outpatients with a negative CUS, a positive rapid ELISA D-dimer test, and a nondiagnostic VP scan or negative spiral CT to prevent overtreatment with anticoagulants. However, the willingness of clinicians and the availability of resources to perform PA is restricted, a fact that has provided an impetus for clinical investigators to search for alternative noninvasive strategies to exclude or detect venous thromboembolism (VTE). Serial CUS testing for the detection of DVT in patients with a low to moderate CP on PE and a nondiagnostic VP scan or negative spiral CT is predicted to be safe and will reduce the need for PA to less than 10% or even less than 5%. This noninvasive serial CUS strategy restricts the need for invasive PA to a minor group of patients (spiral CT and a high CP on PE. Prospective evaluations are warranted to implement and to validate the advantages and the disadvantages of the various combinations of noninvasive strategies and to compare serial CUS testing versus PA in randomized clinical management studies of outpatients with suspected pulmonary embolism.

Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials

DEFF Research Database (Denmark)

Lifson, A; Rhame, F; Bellosa, W

2006-01-01

adjudication between reviewers before diagnostic certainty was assigned. CONCLUSION: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation......PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression...... and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure...

Application of MultiStem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft vs host disease

Directory of Open Access Journals (Sweden)

Bart eVaes

2012-11-01

Full Text Available The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC for treatment of Graft vs Host Disease (GvHD, and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal®; Osiris Therapeutics. This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem® product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products per donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

Science.gov (United States)

Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

2010-11-01

To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

Determination of lactic acid level in systemic liquids in children with progressive encephalopathies.

Science.gov (United States)

Marszał, Elzbieta; Wojaczyńska-Stanek, Katarzyna; Pietruszewski, Jerzy; Emich-Widera, Ewa; Bielińska-Bujniewicz, Eugenia

2002-03-01

This article reports the results of research into the activities of lactic acid concentrations in the body fluids of children with progressive encephalopathies (PE) in comparison to patients with non-progressive encephalopathies (NPE) and those with non-progressive encephalopathies with concomitant epilepsy (NPEE). The study was designed to determine whether there is difference between the serum and CSF lactic acid concentrations in children with progressive encephalopathies (PE), static (non-progressive) encephalopathies (NPE) and non progressive encephalopathies with concomitant epilepsy (NPEE), and whether the clinical status correlates with the concentration of these biochemical markers in children with PE. The assessment involved 138 children of both sexes, whose age ranged between 8 months and 15 years, diagnosed and treated in the Neurology Department at the Pediatric Clinic of the Silesian Medical Academy in Katowice between 1995 and 1997. Lactate concentrations were determined in serum and cerebro-spinal fluid and analyzed statistically. The findings showed higher serum and CSF concentrations in children with PE than in patients who manifested non-progressive forms of encephalopathy. The degree of clinical symptom aggravation in PE children was likewise analyzed and compared to the values of lactate concentrations in body fluids; however, no correlation was found between these parameters. Children with progressive encephalopathies present higher lactate concentrations in serum and cerebrospinal fluid than patients with static (non-progressive) encephalopathy.

Crevicular fluid biomarkers and periodontal disease progression.

Science.gov (United States)

Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

2014-02-01

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation and neuroendocrine tumor syndrome with a homogenous enlargement of the pituitary gland: a case report.

Science.gov (United States)

Aljabban, Lama; Kassab, Lina; Bakoura, Nour Alhuda; Alsalka, Mohammad Fayez; Maksoud, Ismaeil

2016-11-22

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome is a rare pediatric disorder with a variable sequence of clinical presentations, undefined etiology, and high risk of mortality. Our patient presented an unusual course of the disease accompanied by a homogenous mild enlargement of her pituitary gland with an intact pituitary-endocrine axis which, to the best of our knowledge, represents a new finding in rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome. We present a documented case of a 4 years and 8-month-old Syrian Arabic girl with a distinctive course of signs and symptoms of rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome accompanied by mature ganglioneuroma in her chest, a homogenous mild enlargement of her pituitary gland, generalized cortical brain atrophy, and seizures. Three months after her first marked symptoms were noted she had a sudden progression of severe respiratory distress that ended with her death. The findings of this case could increase our understanding of the pathogenetic mechanisms of rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation, and place more emphases on pediatricians to consider rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome whenever early rapid onset of obesity, associated with any malfunction, is observed in children. This knowledge could be lifesaving for children with rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome.

Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

Science.gov (United States)

Leung, Janice M; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Scaglioni, Riccardo; Dai, Darlene; Hague, Cameron; Leipsic, Jonathon; Sin, Don D.; Man, SF Paul; Guaraldi, Giovanni

2016-01-01

Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression. PMID:27902753

A longitudinal study of motor, oculomotor and cognitive function in progressive supranuclear palsy.

Directory of Open Access Journals (Sweden)

Boyd C P Ghosh

Full Text Available We studied the annual change in measures of motor, oculomotor and cognitive function in progressive supranuclear palsy. This had twin objectives, to assess the potential for clinical parameters to monitor disease progression in clinical trials and to illuminate the progression of pathophysiology.Twenty three patients with progressive supranuclear palsy (Richardson's syndrome were compared to 22 matched controls at baseline and 16 of these patients compared at baseline and one year using: the progressive supranuclear palsy rating scale; the unified Parkinson's disease rating scale; the revised Addenbrooke's cognitive examination; the frontal assessment battery; the cubes section of the visual object and space perception battery; the Hayling and Brixton executive tests; and saccadic latencies.Patients were significantly impaired in all domains at baseline. However, cognitive performance was maintained over a year on the majority of tests. The unified Parkinson's disease rating scale, saccadic latency and progressive supranuclear palsy rating scale deteriorated over a year, with the latter showing the largest change. Power estimates indicate that using the progressive supranuclear palsy rating scale as an outcome measure in a clinical trial would require 45 patients per arm, to identify a 50% reduction in rate of decline with 80% power.Motor, oculomotor and cognitive domains deteriorate at different rates in progressive supranuclear palsy. This may be due to differential degeneration of their respective cortical-subcortical circuits, and has major implications for the selection of outcome measures in clinical trials due to wide variation in sensitivity to annual rates of decline.

Chronic progressive lymphoedema in draught horses.

Science.gov (United States)

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.

Clinical profile of subdural hematomas: dangerousness of subdural subacute hematoma.

Science.gov (United States)

Kpelao, E; Beketi, K A; Moumouni, A K; Doleagbenou, A; Ntimon, B; Egbohou, P; Mouzou, T; Tomta, K; Sama, D H; Abalo, A; Walla, A; Dossim, A

2016-04-01

Subacute subdural hematomas are a poorly individualized nosological entity, often equated clinically to chronic subdural hematomas. Yet, their neurological deterioration which is usually rapid seems to distinguish them from chronic subdural hematomas. We wanted to show this dangerousness by establishing the clinically evolving profile of the three types of subdural hematomas. This was a prospective and retrospective study of 63 subdural hematoma (18 acute, 13 subacute, and 32 chronic) patients admitted between 2012 and 2014 in the neurosurgery unit of Lomé University Hospital. Hematomas were classified according to the elapsed time after head injury and blood density on CT. The main parameter studied was the evolution of the Glasgow Coma Score (GCS) in the 3 months following the trauma, enabling to establish an evolving profile of each type of hematoma. The average age of patients was 58.1 years for chronic subdural hematomas and 47.6 years for subacute subdural hematomas. Disease duration before admission was 13.1 days for chronic against 36.6 h for subacute hematoma. The clinical profile shows acute worsening within hours during the second week for patients with subacute hematoma, while it is progressive for patients with chronic hematoma. We noted two deaths, all victims of a subacute hematoma (one operated, one patient waiting for surgery). Iso-density hematoma on CT, especially in a young person, must be considered as a predictive factor of rapid neurological aggravation suggesting an urgent care or increased monitoring by paramedics.

The Clinical Nutrition Research Agenda in Indonesia and beyond: ecological strategy for food in health care delivery.

Science.gov (United States)

Lukito, Widjaja; Wibowo, Lindawati; Wahlqvist, Mark L

2017-06-01

Despite progress with the food-associated health agenda in the public health and clinical domains, much remains to be done in Indonesia. There are reasons to be optimistic which include economic development, increasing literacy, progress towards universal health coverage and community organizational arrangements across the archipelago which focus on health through some 10,000 puskesmas. These community health centres are variably staffed with voluntary cadres from the community, bidans (nurses) and general medical practitioners. For more effective prevention and management of nutritionally-related health problems, innovative community and clinical nutrition research and expertise is required. With rapid urbanisation, the growth of the digital economy, increasing socio-economic inequity and climate change, there are imperatives for ecologically sustainable, nonemployment dependent livelihoods which provide energy, food, water, education and health care security. A relevant health care workforce will include those who research and practice clinical nutrition. Here we gather together an account of an extensive body of published and emerging literature which makes a case collectively for a more ecological approach to nutrition and health and how it might revitalise the Indonesian and other health care systems.

Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells.

Science.gov (United States)

Emami-Shahri, Nia; Foster, Julie; Kashani, Roxana; Gazinska, Patrycja; Cook, Celia; Sosabowski, Jane; Maher, John; Papa, Sophie

2018-03-14

The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19 + B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells. Here we show the utility of the human sodium iodide symporter (hNIS) for the temporal and spatial monitoring of CAR T-cell behavior in a cancer-bearing host. This system provides a clinically compliant toolkit for high-resolution serial imaging of CAR T cells in vivo, addressing a fundamental unmet need for future clinical development in the field.

Mycobacterium grossiae sp. nov., a rapidly growing, scotochromogenic species isolated from human clinical respiratory and blood culture specimens.

Science.gov (United States)

Paniz-Mondolfi, Alberto Enrique; Greninger, Alexander L; Ladutko, Lynn; Brown-Elliott, Barbara A; Vasireddy, Ravikiran; Jakubiec, Wesley; Vasireddy, Sruthi; Wallace, Richard J; Simmon, Keith E; Dunn, Bruce E; Jackoway, Gary; Vora, Surabhi B; Quinn, Kevin K; Qin, Xuan; Campbell, Sheldon

2017-11-01

A previously undescribed, rapidly growing, scotochromogenic species of the genus Mycobacterium (represented by strains PB739 T and GK) was isolated from two clinical sources - the sputum of a 76-year-old patient with severe chronic obstructive pulmonary disease, history of tuberculosis exposure and Mycobacterium avium complex isolated years prior; and the blood of a 15-year-old male with B-cell acute lymphoblastic leukaemia status post bone marrow transplant. The isolates grew as dark orange colonies at 25-37 °C after 5 days, sharing features in common with other closely related species. Analysis of the complete 16S rRNA gene sequence (1492 bp) of strain PB739 T demonstrated that the isolate shared 98.8 % relatedness with Mycobacterium wolinskyi. Partial 429 bp hsp65 and 744 bp rpoB region V sequence analyses revealed that the sequences of the novel isolate shared 94.8 and 92.1 % similarity with those of Mycobacterium neoaurum and Mycobacterium aurum, respectively. Biochemical profiling, antimicrobial susceptibility testing, HPLC/gas-liquid chromatography analyses and multilocus sequence typing support the taxonomic status of these isolates (PB739 T and GK) as representatives of a novel species. Both isolates were susceptible to the Clinical and Laboratory Standards Institute recommended antimicrobials for susceptibility testing of rapidly growing mycobacteria including amikacin, ciprofloxacin, moxifloxacin, doxycycline/minocycline, imipenem, linezolid, clarithromycin and trimethropin/sulfamethoxazole. Both isolates PB739 T and GK showed intermediate susceptibility to cefoxitin. We propose the name Mycobacterium grossiae sp. nov. for this novel species and have deposited the type strain in the DSMZ and CIP culture collections. The type strain is PB739 T (=DSM 104744 T =CIP 111318 T ).

Evaluation of a rapid immunodiagnostic test kit for rabies virus.

Science.gov (United States)

Kang, BoKyu; Oh, JinSik; Lee, ChulSeung; Park, Bong-Kyun; Park, YoungNam; Hong, KyungSoo; Lee, KyungGi; Cho, ByungKi; Song, DaeSub

2007-10-01

A rapid immunodiagnostic test kit for rabies virus detection was evaluated using 51 clinical samples and 4 isolates of rabies virus. The quick detection of rabies virus under field conditions may be helpful in determining if post-exposure prophylaxis is needed, thereby avoiding unnecessary treatments, as well as undue economic burden. There are several widely used diagnostic methods for rabies, including fluorescent antibody tests, reverse transcription polymerase chain reaction, and electron microscopy; however, these methods include time-consuming, intricate, and costly procedures. The rapid immunodiagnostic test was able to detect rabies virus in clinical samples, including brain tissue and saliva, in addition to 10(3.2) 50% lethal dose (LD(50))/mL cell-adapted rabies virus. The assay was not cross-reactive with non-rabies virus microbes. When the performance of the rapid immunodiagnostic test was compared to a fluorescent antibody test, the rapid immunodiagnostic test had a sensitivity of 91.7% and specificity of 100% (95.8% CI).

Clinical-Diagnostic Features of Duchenne Muscular Dystrophy in Children

Directory of Open Access Journals (Sweden)

Umida T. Omonova

2013-12-01

Full Text Available Duchenne Muscular Dystrophy (DMD is a severe, progressive disease that affects about 1 out of every 5,000 male infants; this is the most destructive of all muscular dystrophies, which worsens rapidly. In this study, we performed a clinical analysis of 37 children with DMD. They ranged in age from 3 to 15 years, mean age being 7.8±0.48 years. The mean age at onset was 4.3±0.36 years and ranged from birth to 8 years. The biochemical examination included the determination of the serum levels of the following enzymes, AST, ALT, CPK-MM, and LDH. A genealogical analysis was conducted among 240 first-degree relatives of children with DMD. Electroneuromyography examination included registration of the biopotentials of the hand and foot muscles, measurement of the muscle response (M-wave and the late-evoked responses. The clinical-diagnostic features of DMD in children were characterized.

Nosocomial Legionnaires’ Disease: Clinical and Radiographic Patterns

Directory of Open Access Journals (Sweden)

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.

[Ethical principles of clinical trials in minors].

Science.gov (United States)

Koch, H J; Raschka, C

2002-12-05

Clinical trials in volunteers and patients are essential to ensure rational treatment of patients. As a rule, drugs are routinely developed for adults, but children are excluded. A major reason for this restriction are ethical justifications, in particular the lack of autonomy on the part of children. The principle of fairness, however, requires that everyone should benefit from progress. Industry, science and society are therefore called upon to find ways of making available safe and adequate treatment for children as quickly as possible, by defining the required conditions for pediatric clinical trials. Important principles are minimal risk, minimal invasivity, rapid decision-making, and careful documentation of trial results. Dynamic ethical principles, such as autonomy and competence in adolescents must be considered on equal footing with existing international GCP guidelines. Aspects of child psychology indicate that the autonomy of adolescents should be respected. Where economic incentives for such trials are absent, for example, in the case of non-pharmacological problems, pediatric trials must be considered a task for society as a whole.

Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

Science.gov (United States)

Lamm, Donald; Persad, Raj; Brausi, Maurizio; Buckley, Roger; Witjes, J Alfred; Palou, Joan; Böhle, Andreas; Kamat, Ashish M; Colombel, Marc; Soloway, Mark

2014-01-01

Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Rapid and Automated Determination of Plutonium and Neptunium in Environmental Samples

DEFF Research Database (Denmark)

Qiao, Jixin

This thesis presents improved analytical methods for rapid and automated determination of plutonium and neptunium in environmental samples using sequential injection (SI) based chromatography and inductively coupled plasma mass spectrometry (ICP-MS). The progress of methodology development...... and optimization for rapid determination of plutonium in environmental samples using SIextraction chromatography prior to inductively coupled plasma mass spectrometry (Paper III); (3) Development of an SI-chromatographic method for simultaneous determination of plutonium and neptunium in environmental samples...... for rapid and simultaneous determination of plutonium and neptunium within an SI system (Paper VI). The results demonstrate that the developed methods in this study are reliable and efficient for accurate assays of trace levels of plutonium and neptunium as demanded in different situations including...

Nanoscale microstructure effects on hydrogen behavior in rapidly solidified aluminum alloys

Energy Technology Data Exchange (ETDEWEB)

Tashlykova-Bushkevich, Iya I. [Belarusian State University of Informatics and Radioelectronics, Minsk (Belarus)

2015-12-31

The present work summarizes recent progress in the investigation of nanoscale microstructure effects on hydrogen behavior in rapidly solidified aluminum alloys foils produced at exceptionally high cooling rates. We focus here on the potential of modification of hydrogen desorption kinetics in respect to weak and strong trapping sites that could serve as hydrogen sinks in Al materials. It is shown that it is important to elucidate the surface microstructure of the Al alloy foils at the submicrometer scale because rapidly solidified microstructural features affect hydrogen trapping at nanostructured defects. We discuss the profound influence of solute atoms on hydrogen−lattice defect interactions in the alloys. with emphasis on role of vacancies in hydrogen evolution; both rapidly solidified pure Al and conventionally processed aluminum samples are considered.

Progress in the last decade in our understanding of primary progressive aphasia

Directory of Open Access Journals (Sweden)

Ratnavalli Ellajosyula

2010-10-01

Full Text Available Primary progressive aphasia (PPA is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA, semantic dementia (SD, and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca′s area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick′s disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer′s disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.

[Progress in methodological characteristics of clinical practice guideline for osteoarthritis].

Science.gov (United States)

Xing, D; Wang, B; Lin, J H

2017-06-01

At present, several clinical practice guidelines for the treatment of osteoarthritis have been developed by institutes or societies. The ultimate purpose of developing clinical practice guidelines is to formulate the process in the treatment of osteoarthritis effectively. However, the methodologies used in developing clinical practice guidelines may place an influence on the transformation and application of that in treating osteoarthritis. The present study summarized the methodological features of individual clinical practice guideline and presented the tools for quality evaluation of clinical practice guideline. The limitations of current osteoarthritis guidelines of China are also indicated. The review article might help relevant institutions improve the quality in developing guide and clinical transformation.

Chronic Inflammatory Demyelinating Polyneuropathy in Children: A Review of Clinical Characteristics and Recommendations for Treatment

Directory of Open Access Journals (Sweden)

Narges Karimi

2015-07-01

Full Text Available Context: Chronic inflammatory demyelinating polyradiculopathy (CIDP is an acquired and autoimmune neuropathy, characterized by a chronic, rapidly progressive, symmetric weakness. In children, abnormal gait is as a first symptom of muscle weakness. Evidence Acquisition: The diagnosis of CIDP is on the basis of clinical characteristics, electrodiagnostic that shows the severity of the disease, lumbar puncture and spine magnetic resonance imaging (MRI. Results: The first-line treatments in childhood CIDP are intravenous immunoglobulin (IVIG, corticosteroids, and plasmapheresis. Response to first-line therapies is usually satisfactory; nevertheless, recommendations regarding the choice of second-line therapy can only be prepared on the basis of the existing practice described in some of the case reports. Conclusions: This review demonstrated the clinical presentation, diagnosis, and treatment of childhood CIDP.

Measuring the progression of idiopathic Parkinson's disease with [123I] β-CIT SPECT

International Nuclear Information System (INIS)

Staffen, W.; Mair, A.; Unterrainer, J.; Trinka, E.; Ladurner, G.

2000-01-01

Idiopathic Parkinson's disease (PD) is the most common neuro degenerative disorder. An important step in diagnosing the disease has been achieved with the development of the cocaine derivative [ 123 I] β-CIT for single photon emission computed tomography (SPECT). The aim of this study was to demonstrate the disease progression by repeated measuring presynaptic dopamine transporter density and relating it to clinical data. The presynaptic dopamine, transporter density of 15 PD patients was measured two times with a mean interval of 15 months. All patients were clinically assessed at the time of the experiments according to the classification scheme of Hoehn and Yahr. 11 healthy volunteers were used as a control group. [ 123 I] β-CIT was injected intravenously and measured with a triple-headed camera twenty hours later. The pictures were evaluated semi quantitatively by using the ratio of specific to non-displaceable binding. Presynaptic dopamine transporter density differed significantly between controls and PD patients. A significant correlation between imaging data and clinical stages (H/Y I 27 %, H/Y II -40 %, H/Y III 58 %) was observed for the patient group in the initial experiment. The subsequent decrease of dopamine transporter binding depended on the initial clinical stage (H/Y I -6.81 %; H/Y II -6.05 %; H/Y III -1.25 %) of the patients, and regression analysis revealed that. 91.4 % of the variance of the second measurement were predicted by the initial measurement. No correlations were found for age, gender and disease progression. All patients were treated with L-DOPA and those given a higher dose showed a more rapid decrease of dopamine transporter density. This result could be interpreted as an indication for in vivo neurotoxicity of high concentrations of L-DOPA. We conclude that combining [ 123 I] β-CIT with SPECT imaging is not only a powerful tool for diagnosing PD patients, but may also be used to demonstrate neuro degeneration in vivo. (author)

Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

2012-06-15

To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

Goodpasture's Syndrome due to IgA in a patient with clinical diagnosis of Henoch Schonlein's purpura

International Nuclear Information System (INIS)

Restrepo Cesar A

2005-01-01

This is a case of a 23 year old woman with an initial clinical syndrome compatible with glomerulonephritis of uncertain origin, who later showed lesions of purpuric rash characteristics of Henoch- Schonlein Purpura and then complicated with a pulmonary hemorrhage and a rapidly progressive glomerulonephritis, with a mixed lung-kidney syndrome. The renal biopsy showed presence of linear deposits of immunoglobulin A and extra capillary proliferative changes. The case was concluded corresponding to Goodpasture's syndrome for antibodies antiglomerular basement membrane of the type of IgA in the context of a Henoch-Schonlein Purpura.

Nonoperative Management, Rehabilitation, and Functional and Clinical Progression of Osteitis Pubis/Pubic Bone Stress in Professional Soccer Players: A Case Series.

Science.gov (United States)

McAleer, Stephen S; Lippie, Ed; Norman, Darcy; Riepenhof, Helge

2017-09-01

Study Design Case series. Background Pubic bone stress (PBS) is a common acute or chronic response of the pelvis in sports where sprinting, kicking, twisting, and cutting are the dominant movements. There are few nonoperative rehabilitation strategies for the condition reported in the literature, and the outcome of conservative treatment has not been documented. Case Description Five professional and academy soccer players complaining of pubic symphysis pain, confirmed as PBS on magnetic resonance imaging and objective assessment, were treated with a nonoperative rehabilitation program that featured functional and clinical objective markers as progression criteria. Interventions in the acute phase included pharmacological and physical therapeutic modalities to reduce pain initially. Rehabilitation management focused on improving range of motion at the hips and thorax, adductor strengthening, trunk and lumbopelvic stability, gym-based strength training, and field-based rehabilitation and conditioning. Clinical follow-up was performed at least 8 months following return to play. Outcomes All players demonstrated reduced or resolved pain, increased adductor squeeze strength, and return to pain-free training and match play. Return-to-training time averaged 40.6 days (range, 30-60 days) and return to play averaged 49.4 days (range, 38-72 days) within the 5 players. At final follow-up (mean, 29.6 months; range, 16-33 months), there had been no recurrences. Discussion This report of 5 cases suggests that a nonoperative protocol, using clinical and functional progression criteria, may be successful in rehabilitating athletes with PBS for return to sport within 11 weeks. Level of Evidence Therapy, level 4. J Orthop Sports Phys Ther 2017;47(9):683-690. Epub 3 Aug 2017. doi:10.2519/jospt.2017.7314.

Primary progressive multiple sclerosis in the Polish population

Directory of Open Access Journals (Sweden)

Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

Autologous hematopoietic stem cell transplantation in combination with immunoablative protocol in secondary progressive multiple sclerosis: A 10-year follow-up of the first transplanted patient

Directory of Open Access Journals (Sweden)

Obradović Dragana

2016-01-01

Full Text Available Introduction. Multiple sclerosis (MS is an immunemediated disease of the central nervous system that affects young individuals and leads to severe disability. High dose immunoablation followed by autologous hemopoietic stem cell transplantation (AHSCT has been considered in the last 15 years as potentialy effective therapeutic approach for agressive MS. The most recent long-time follow-up results suggest that AHSCT is not only effective for highly aggressive MS, but for relapsing-remitting MS as well, providing long-term remission, or maybe even cure. We presented a 10- year follow-up of the first MS patient being treated by immunoablation therapy and AHSCT. Case report. A 27-year-old male experienced the first symptoms - intermitent numbness and paresthesia of arms and legs of what was treated for two years by psychiatrist as anxiety disorder. After he developed severe paraparesis he was admitted to the Neurology Clinic and diagnosed with MS. Our patient developed aggressive MS with frequent relapses, rapid disability progression and transition to secondary progressive form 6 years after MS onset [the Expanded Disability Status Scale (EDSS 7.0 Ambulation Index (AI 7]. AHSCT was performed, cyclophosphamide was used for hemopoietic stem cell mobilization and the BEAM protocol was used as conditionig regimen. No major adverse events followed the AHSCT. Neurological impairment improved, EDSS 6.5, AI 6 and during a 10-year followup remained unchanged. Brain MRI follow-up showed the absence of gadolinium enhancing lesions and a mild progression of brain atrophy. Conclusion. The patient with rapidly evolving, aggressive, noninflammatory MS initialy improved and remained stable, without disability progression for 10 years, after AHSCT. This kind of treatment should be considered in aggressive MS, or in disease modifying treatment nonresponsive MS patients, since appropriately timed AHSCT treatment may not only prevent disability progression but reduce

Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

LENUS (Irish Health Repository)

Quintyne, Keith Ian

2011-09-01

The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

International Nuclear Information System (INIS)

Kidwai, A.A.; Jamal, Q.; Mehrunnisa, S.; Farooqi, F.R.

2010-01-01

Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

Specific magnetic resonance imaging findings in patient with progressive supranuciear palsy

International Nuclear Information System (INIS)

Vuchkova, R.; Zlatareva, D.

2013-01-01

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease. The clinical symptoms are vertical supranuclear palsy, gait and postural instability, cognitive deficit, Parkinsonism. It is not always possible to differentiate clinically PSP from other atypical Parkinsonian syndromes and from Parkinson disease. We present a case of 56-years old women with clinically suspected PSP. The typical magnetic resonance findings were of most importance in diagnosis. For diagnosing the disease by means of neuroimaging it is necessary to analyze the sagittal MR images what is achievable in daily routine practice without additional software and post processing. (authors)

Rapid lysostaphin test to differentiate Staphylococcus and Micrococcus species.

Science.gov (United States)

Geary, C; Stevens, M

1986-01-01

A rapid, simple lysostaphin lysis susceptibility test to differentiate the genera Staphylococcus and Micrococcus was evaluated. Of 181 strains from culture collections, 95 of 95 Staphylococcus strains were lysed, and 79 of 79 Micrococcus strains were not lysed. The seven Planococcus strains were resistant. Clinical isolates (890) were tested with lysostaphin and for the ability to produce acid from glycerol in the presence of erythromycin. Overall agreement between the methods was 99.2%. All clinical Micrococcus strains (43) were resistant to lysostaphin, and all clinical Staphylococcus strains (847) were susceptible. Seven of the Staphylococcus strains did not produce acid from glycerol in the presence of erythromycin. This lysostaphin test provides results in 2 h. It is easier to perform than previously described lysostaphin lysis methods. It is also more rapid and accurate than the glycerol-erythromycin test. PMID:3519667

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

Science.gov (United States)

Grignani, Giovanni; Palmerini, Emanuela; Ferraresi, Virginia; D'Ambrosio, Lorenzo; Bertulli, Rossella; Asaftei, Sebastian Dorin; Tamburini, Angela; Pignochino, Ymera; Sangiolo, Dario; Marchesi, Emanuela; Capozzi, Federica; Biagini, Roberto; Gambarotti, Marco; Fagioli, Franca; Casali, Paolo Giovanni; Picci, Piero; Ferrari, Stefano; Aglietta, Massimo

2015-01-01

Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374. We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Although the combination of sorafenib and everolimus showed activity as a further-line treatment

Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression

Science.gov (United States)

Rebeiro, Peter F; Cesar, Carina; Shepherd, Bryan E; De Boni, Raquel B; Cortés, Claudia P; Rodriguez, Fernanda; Belaunzarán-Zamudio, Pablo; Pape, Jean W; Padgett, Denis; Hoces, Daniel; McGowan, Catherine C; Cahn, Pedro

2016-01-01

Introduction We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission. Conclusions HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings. PMID:27065108

Recent technological updates and clinical applications of induced pluripotent stem cells.

Science.gov (United States)

Diecke, Sebastian; Jung, Seung Min; Lee, Jaecheol; Ju, Ji Hyeon

2014-09-01

Induced pluripotent stem cells (iPSCs) were first described in 2006 and have since emerged as a promising cell source for clinical applications. The rapid progression in iPSC technology is still ongoing and directed toward increasing the efficacy of iPSC production and reducing the immunogenic and tumorigenic potential of these cells. Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-specific iPSCs continues to expand our knowledge regarding the pathophysiology and prospective treatment of rare disorders. Furthermore, autologous stem cell therapy with patient-specific iPSCs shows great propensity for the minimization of immune reactions and the provision of a limitless supply of cells for transplantation. In this review, we discuss the recent updates in iPSC technology and the use of iPSCs in disease modeling and regenerative medicine.

Short term clinical disease progression in HIV-1 positive patients taking combination antiretroviral therapy : The EuroSIDA risk-score

DEFF Research Database (Denmark)

Mocroft, A; Ledergerber, B; Zilmer, K

2007-01-01

/death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). RESULTS: In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval...... (CI), 2.7-3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk...... in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56-2.84) in EuroSIDA and 2.88 (95% CI, 2.75-3.02) in SHCS. CONCLUSIONS: A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk...

Rapid in situ gamma spectrometric determination of fallout radioactivity in the environment. Progress report

International Nuclear Information System (INIS)

Zombori, Peter

1995-01-01

The main aim of the present CRP is to identify the existing analytical methods and develop new ones, if possible, which provide rapid, reliable, and detailed information on the radioactive contamination of the environment after a major nuclear accident. Gamma spectrometry has long been regarded as one of the most applicable radioanalytical techniques but its use for environmental studies requires some further considerations. There are two possible approaches to measure environmental radioactivity: (a) taking samples of the different environmental media and measuring them in a laboratory or (b) taking the spectrometer to the place of interest and making in situ measurements. In the former case sampling is a crucial factor hindering the rapid analysis while the latter case is not always reliable due to the problems and uncertainties of the measurement interpretation. The application of in situ gamma spectrometry for the determination of environmental radioactivity has become increasingly attractive since the advent of the high resolution semiconductor gamma detectors, especially, more recently, portable high purity Ge diodes (HpGe). The applicability of this technique was very well proved after the Chernobyl reactor accident when in situ spectrometry played an important role in the rapid evaluation of the fall-out situation. Our measurements provided information on the amount and composition of the radioactive contamination of the ground surface already in the first hours. These measurements enabled us to predict the time variation of the environmental radioactivity after the stabilization of the situation. The portability of the system was an important factor in performing a rapid and efficient survey in different parts of the country. A serious disadvantage of this method is, however, that it requires some knowledge about the radionuclide distribution in the soil, which is normally determined by tedious and time consuming sample analysis of the different soil

Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers.

Science.gov (United States)

Handels, Ron L H; Vos, Stephanie J B; Kramberger, Milica G; Jelic, Vesna; Blennow, Kaj; van Buchem, Mark; van der Flier, Wiesje; Freund-Levi, Yvonne; Hampel, Harald; Olde Rikkert, Marcel; Oleksik, Ania; Pirtosek, Zvezdan; Scheltens, Philip; Soininen, Hilkka; Teunissen, Charlotte; Tsolaki, Magda; Wallin, Asa K; Winblad, Bengt; Verhey, Frans R J; Visser, Pieter Jelle

2017-08-01

We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers. Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up. An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

Science.gov (United States)

Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Clinical predictors of outcome in vitiligo

Directory of Open Access Journals (Sweden)

Dave Shriya

2002-11-01

Full Text Available The significant inter-patient variability in progression, and response to therapy makes it a great challenge for the physician to predict the outcome of vitiligo at the very outset. Subjective factors like stress, pregnancy, sunburn and illness have been identified as aggravating factors for vitiligo. However, a few studies have evaluated the statistical significance of objective clinical parameters in predicting the outcome of vitiligo. Our retrospective analysis of 199 consecutive patients with vitiligo who presented to our OPD was aimed at evaluation of these objective clinical parameters utilizing a standard proforma. Patients already on treatment, and those with duration of disease less than 6 months were excluded from the study. Progression was defined as an increase in size or number of lesions in the 3 months prior to presentation. In all 76. 9% patients had progression of vitiligo. The clinical parameters significantly associated with progression were a positive family history (p=0. 027, mucosal involvement (p=0. 032, Koebner′s phenomenon (p=0. 036 and nonsegmental vitiligo (p=0. 033. Thrichrome sign, leucotrichia, longer duration and higher age at onset did not correlate significantly with progression. The one significant observation that we found to have the poor prognostic implication in vitiligo is the presence of mucosal vitiligo. The clinical prediction of disease progression at the outset enables the physician to set realistic treatment goals and optimize the therapeutic regimen for the individual patient.

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

Science.gov (United States)

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-10-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties.

Science.gov (United States)

Panahifar, A; Jaremko, J L; Tessier, A G; Lambert, R G; Maksymowych, W P; Fallone, B G; Doschak, M R

2014-10-01

We sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA. Post-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment. Disease progression was monitored utilizing micro-magnetic resonance imaging (MRI), micro-computed tomography (CT) and histology. Pertinent features such as osteophytes, subchondral sclerosis, joint effusion, bone marrow lesion (BML), cysts, loose bodies and cartilage abnormalities were included in designing a sensitive multi-modality based scoring system, termed the rat arthritis knee scoring system (RAKSS). Overall, an inter-observer correlation coefficient (ICC) of greater than 0.750 was achieved for each scored feature. None of the treatments prevented cartilage loss, synovitis, joint effusion, or sclerosis. However, celecoxib significantly reduced osteophyte development compared to placebo. Although signs of inflammation such as synovitis and joint effusion were readily identified at 4 weeks post-operation, we did not detect any BML. We report the development of a sensitive and reliable multi-modality scoring system, the RAKSS, for evaluation of OA severity in pre-clinical animal models. Using this scoring system, we found that celecoxib prevented enlargement of osteophytes in this animal model of PTOA, and thus it may be useful in preventing OA progression. However, it did not show any chondroprotective effect using the recommended dose. In contrast, high dose glucosamine had no measurable effects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Rapid MR imaging

International Nuclear Information System (INIS)

Edelman, R.R.; Buxton, R.B.; Brady, T.J.

1988-01-01

Conventional magnetic resonance (MR) imaging methods typically require several minutes to produce an image, but the periods of respiration, cardiac motion and peristalsis are on the order of seconds or less. The need to reduce motion artifact, as well as the need to reduce imaging time for patient comfort and efficiency, have provided a strong impetus for the development of rapid imaging methods. For abdominal imaging, motion artifacts due to respiration can be significantly reduced by collecting the entire image during one breath hold. For other applications, such as following the kinetics of administered contrast agents, rapid imaging is essential to achieve adequate time resolution. A shorter imaging time entails a cost in image signal/noise (S/N), but improvements in recent years in magnet homogeneity, gradient and radiofrequency coil design have led to steady improvements in S/N and consequently in image quality. For many chemical applications the available S/N is greater than needed, and a trade-off of lower S/N for a shorter imaging time is acceptable. In this chapter, the authors consider the underlying principles of rapid imaging as well as clinical applications of these methods. The bulk of this review concentrates on short TR imaging, but methods that provide for a more modest decrease in imaging time as well as or those that dramatically shorten the imaging time to tens of milliseconds are also discussed

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

Science.gov (United States)

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies

Directory of Open Access Journals (Sweden)

Giovanni Barillari

2018-05-01

Full Text Available Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN. CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC, a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV, as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s of its development. This article reviews published work concerning: (i the role of HPV proteins (including HPV-E5, E6 and E7 and of matrix-metalloproteinases (MMPs in CIN evolution into invasive CC; and (ii the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women.

Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.

Science.gov (United States)

Piguet, Françoise; de Montigny, Charline; Vaucamps, Nadège; Reutenauer, Laurence; Eisenmann, Aurélie; Puccio, Hélène

2018-05-28

Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Introduction to the Special Issue on Clinical Neuropsychology of Movement Disorders.

Science.gov (United States)

Tröster, Alexander I