Full Text Available In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70 deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ deficiency. As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID patients were studied: 1 T-negative PID (cartilage-hair hypoplasia and 4 T-positive PID (2 common immune deficiency (CID, 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease. Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982 were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.
Full Text Available Fatal-disseminated Bacillus Calmette Guerin (BCG disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.
Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.
Bacalhau, S; Freitas, C; Valente, R; Barata, D; Neves, C; Schäfer, K; Lubatschofski, A; Schulz, A; Farela Neves, J
In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highligh...
Sanchez-Alegre, M. L.; Casanova, A.; Delgado, J.; Relanzon, S.
We describe a case of lymphoid nodular hyperplasia in a woman with severe combined immunodeficiency disease. the patient complained of constipation and episodes of abdominal pain, and examination revealed the presence of a large abdominal mass. The diagnosis was suspected on the basis of the initial radiological studies, but intestinal biopsy was necessary to rule out lymphomatous involvement. We point out the radiological features of this entity which, despite the fact that it may be a chance finding of no pathological significance, requires special attention, especially in immuno deficient individuals. (Author) 10 refs
Piro, M; Benjouad, A; Tligui, N S; El Allali, K; El Kohen, M; Nabich, A; Ouragh, L
Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian or crossbred Arabian horses. The genetic defect responsible was previously identified as a 5-base pair deletion in the gene encoding the catalytic subunit of the DNA dependant protein kinase (DNA-PKcs). This study was carried out to determine the frequency of SCID and identify horses carrying the gene for SCID among Arabian and Arabian crossbred stallions and mares in Morocco using a DNA-based test. Twenty-one horses were SCID carriers: 14 (7%) Arabians, 6 (4%) Arab-Barbs and one (33%) Anglo-Arab. After analysing their genealogy, 3 imported stallions were identified that disseminated the mutant gene of DNA-PKcs in Morocco.
Aitken, D.A.; Kleijer, W.J.; Niermeijer, M.F.; Galjaard, H.; Herbschleb-Voogt, E.
A pregnancy at risk for adenosine deaminase deficiency and severe combined immunodeficiency disease has been investigated by assay of adenosine deaminase activity in cultured amniotic fluid cells using a microradioassay. A low-normal level of consistent with heterozygote status in the foetus was found and confirmed after birth by assay of red cell and fibroblast adenosine deaminase activities. It is suggested that the radioassay method offers significant advantages in sensitivity and specificity over the standard spectrophotometric procedure. (author)
... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...
Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M
Brian T Kelly,1 Jonathan S Tam,1 James W Verbsky,1,2 John M Routes1,2 1Department of Pediatrics, 2Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA Abstract: Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diag...
Full Text Available Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. To date, eight cases of lymphomas have been described in ADA-SCID patients. Here we report the first case of plasmablastic lymphoma occurring in a young adult with ADA-SCID on long-term ERT, which turned out to be Epstein–Barr virus associated. The patient previously received infusions of genetically modified T cells. A cumulative analysis of the eight published cases of lymphoma from 1992 to date, and the case here described, reveals a high mortality (89%. The most common form is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT. The significant incidence of immunodeficiency-associated lymphoproliferative disorders and poor survival of patients developing this complication highlight the priority in finding a prompt curative treatment for ADA-SCID.
... Severe Combined Immunodeficiency National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 links) Boston Children's Hospital Genetic Science Learning Center, University of Utah Great Ormond ...
Stanton, B F; Li, X; Galbraith, J; Feigelman, S; Kaljee, L
To evaluate the success of efforts to educate youth not only to use prescription contraceptives to avoid pregnancy, but also to use condoms to avoid sexually transmitted diseases, including infection with the human immunodeficiency virus. Longitudinal study of 383 African-American youth aged 9 to 15 years enrolled in a randomized, controlled trial of an acquired immunodeficiency syndrome (AIDS) risk reduction intervention. Data about contraceptive practices were obtained at baseline and 6, 12, and 18 months later using a culturally and developmentally appropriate risk assessment tool administered with "talking" computers (Macintosh, Apple Computer Inc, Cupertino, Calif). Approximately three fourths of sexually active youth used some form of contraception in each 6-month round, with almost half of the youth using combinations of contraceptives. Among all youth at baseline and among control youth throughout the study, more than half used condoms and more than two thirds who used oral contraceptives also used condoms. Receipt of an AIDS education intervention was associated with use of more effective contraceptive practices (eg, condoms and another prescription or nonprescription method of birth control). After receiving the intervention, more than 80% of the youth who used oral contraceptives also used condoms. Contraceptive practices showed considerable stability. Knowledge about AIDS was positively associated with use of more effective contraceptive methods. Many youth are using condoms and prescription birth control simultaneously, and these use rates can be increased through AIDS education interventions.
Sanem Eren Akarcan
Full Text Available Chronic Mucocutaneous Candidiasis (CMC is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF (c.1154 C>T, p.Thr385Met in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.
Yulish, B.S.; Stern, R.C.; Polmar, S.H.
A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions
Sanchez-Alegre, M. L.; Casanova, A.; Delgado, J.; Relanzon, S. [Hospital General Universitario Gregorio Maranon. Madrid (Spain)
We describe a case of lymphoid nodular hyperplasia in a woman with severe combined immunodeficiency disease. the patient complained of constipation and episodes of abdominal pain, and examination revealed the presence of a large abdominal mass. The diagnosis was suspected on the basis of the initial radiological studies, but intestinal biopsy was necessary to rule out lymphomatous involvement. We point out the radiological features of this entity which, despite the fact that it may be a chance finding of no pathological significance, requires special attention, especially in immuno deficient individuals. (Author) 10 refs.
Kelsen, Judith R; Sullivan, Kathleen E
Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.
Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S
Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients....... In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression...... plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages...
Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.
Panch, Sandhya R.; Yau, Yu Ying; Kang, Elizabeth M.; De Ravin, Suk See; Malech, Harry L.; Leitman, Susan F.
Background G-CSF mobilized autologous hematopoietic progenitor cells (HPC) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients. Study Design and Methods We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age, weight and G-CSF dose-matched healthy allogeneic controls. Results In subjects aged ≤20 years, day 5 pre-apheresis circulating CD34+ counts were significantly lower in CGD and SCID than in controls; mean peak CD34+ cells 58, 64, and 87/uL, respectively, p=0.01. The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiency 40%, 63% and 57%, respectively, p=0.003. In subjects >20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cells 41 and 113/uL, respectively, p<0.0001. In a multivariate analysis, lower sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization, p=0.007. In SCIDs, CD34 collection efficiency was positively correlated with higher red cell indices (MCV: R2=0.77; MCH: R2=0.94; MCHC: R2=0.7, p<0.007) but not hemoglobin. Conclusions CGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation/infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased red cell size and density may impair apheresis cell separation mechanics. PMID:25143186
Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael
To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of 'X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia' (XMEN) disease and its clinical implications. The magnesium transporter protein MAGT1 participates in the intracellular magnesium ion (Mg) homeostasis and facilitates a transient Mg influx induced by the activation of the T-cell receptor. Loss-of-function mutations in MAGT1 cause an immunodeficiency named 'XMEN syndrome', characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T-cell activation and decreased cytolytic function of natural killer (NK) and CD8 T cells because of decreased expression of the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1. XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches.
Campbell, T M; Studdert, M J; Ellis, W M; Paton, C M
A foal with primary severe combined immunodeficiency, diagnosed within the first two weeks of life, was maintained with its dam in semi-isolation. The foal received continuous prophylactic antibiotic therapy, plasma from a sibling hyperimmunised with equine adenovirus vaccine, and intensive general nursing care. A full sibling female was selected as a bone marrow donor on the basis of red blood cell cross-matching and mixed lymphocyte reactions. Cyclophosphamide was given before two bone marrow transfusions at 35 and 73 days of age. To prevent graft versus host disease graft versus host disease the foal was maintained on methotrexate therapy. Reconstitution was not achieved nor were there signs of graft versus host disease. The foal died suddenly four days after the second bone marrow transfer when 77 days old. It had remained clinically free of any life threatening infectious disease and at necropsy a remarkable degree of freedom from infectious disease was confirmed. The most notable necropsy findings were bilateral nephrosis and myocardial degeneration and fibrosis. The likely cause of death was an electrolyte imbalance, particularly hypokalaemia, which secondarily affected the myocardium. Renal toxicity caused by the cytotoxic drugs, especially cyclophosphamide, may have contributed to the electrolyte imbalance.
Full Text Available Primary immunodeficiency diseases (PID include over 250 diverse disorders. The current study assessed management of PID by family practice physicians. The American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Committee and the Immune Deficiency Foundation conducted an incentivized mail survey of family practice physician members of the American Medical Association and the American Osteopathic Association in direct patient care. Responses were compared with subspecialist immunologist responses from a similar survey. Surveys were returned by 528 (of 4500 surveys mailed family practice physicians, of whom 44% reported following ≥1 patient with a PID. Selective immunoglobulin A (IgA, deficiency (21%, and chronic granulomatous disease (11% were most common and were followed by significantly more subspecialist immunologists (P<.0001. Use of intravenously administered Ig, and live viral vaccinations across PID was significantly different (P<.0001. Few family practice physicians were aware of professional guidelines for diagnosis and management of PID (4% vs. 79% of subspecialist immunologists, P<.0001. Family practice physicians will likely encounter patients with a PID diagnoses during their career. Differences in how family practice physicians and subspecialist immunologists manage patients with PID underscore areas where improved educational and training initiatives may benefit patient care.
Scott, Angela; Glover, Jason; Skoda-Smith, Suzanne; Torgerson, Troy R; Xu, Min; Burroughs, Lauri M; Woolfrey, Ann E; Fleming, Mark D; Shimamura, Akiko
Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications. © 2015 Wiley Periodicals, Inc.
Full Text Available Late onset combined immunodeficiency (LOCID is a recently described variant of common variable immunodeficiency (CVID, involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP, subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID. Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses.
Lundgren, J D; Orholm, Marianne; Lundgren, B
cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....
Han, Tae Il; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo
Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy
Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)
Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.
Background: The Human Immunodeficiency Virus (HIV) epidemic is more pronounced in sub-Saharan Africa. The ever-increasing prevalence of HIV infection and the continued improvement in clinical management has increased the likelihood of these patients being managed by healthcare workers. The aim of the review ...
Ramsøe, K; Skinhøj, P; Andersen, V
Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA......-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had...
Full Text Available Background: Common variable immunodeficiency (CVI gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%. Case report: We present the case of a patient with CVI with digestive symptoms being diagnosed of Crohn-like disease with extent ileal affectation. The main treatment of these patients is the same as classical Crohn disease although in the most severe cases, as this one, the use of immunosupresors is necessary. At this time the patient remains on clinical remmision with infliximab. She presented a previous adverse reaction with adalimumab. Discussion: The few case series in this pathology makes the treatment with immunomodulators in this immunodeficiency a real diagnostic and therapeutic challenge.
Saldaña-Dueñas, Cristina; Rubio-Iturria, Saioa
Background: Common variable immunodeficiency (CVI) gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%). Case report: We present the case of a patient with CVI ...
Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively
Arslan, Sevket; Ucar, Ramazan; Caliskaner, Ahmet Zafer; Reisli, Ismail; Guner, Sukru Nail; Sayar, Esra Hazar; Baloglu, Ismail
The European Society of Immunodeficiency (ESID) developed 6 warning signs to promote the awareness of adult primary immunodeficiency disease (PID). To screen adult patients for the presence of PID using these 6 warning signs to determine the effectiveness of this protocol. Questions related to the ESID warning signs for adult PID were added to the standard outpatient clinic file system and asked of 3,510 patients who were admitted to our clinic for any reason. Patients with signs and/or suspicion of PID based on their medical history underwent immunologic investigation. In total, 24 patients were diagnosed as having a PID. The most common reason that patients with PID were admitted was frequent infection (n=18 [75%]), and the most common PID subgroup was common variable immunodeficiency (n=12 [50%]). Twenty patients with PID had at least one positive finding according to the ESID warning signs. Two patients with gastrointestinal concerns and 2 with dermatologic symptoms were also diagnosed as having a PID, although they did not have any of the ESID warning signs. The ESID warning signs do not specify the need for symptoms to diagnose a PIDs and do not include a comprehensive list of all signs and symptoms of PIDs. As a result, more than infection-centric questions are needed to identify adult patients with immunodeficiencies. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Full Text Available Newborn screening (NBS programs for severe combined immunodeficiency (SCID, the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC quantification in dried blood spots (DBS has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.
Vania López Rodríguez; Emilio Carpio Muñoz; Vicente Fardales Macías; Iralys Benítez Guzmán
Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determi...
Full Text Available Quantification of the T cell receptor excision circles (TRECs has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.
Abolhassani, Hassan; Edwards, Emily S. J.; Ikinciogullari, Aydan
In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma...... is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70-CD27 interactions therefore play a nonredundant role in T and B cell-mediated immunity, especially for protection against EBV and humoral immunity....
van den Berg, H.; Wage, K.; Burggraaf, J. D.; Peters, M.
In an infant with skeletal anomalies and haemolytic disease, intestinal perforation was caused by necrosis of an as yet undetected B-cell lymphoma. Severe combined immunodeficiency with short-limbed skeletal dysplasia was diagnosed. This is the first published report of a patient with this syndrome
Marilia Pyles Patto Kanegae
Full Text Available Objective: To apply, in Brazil, the T-cell receptor excision circles (TRECs quantification technique using real-time polymerase chain reaction in newborn screening for severe combined immunodeficiency and assess the feasibility of implementing it on a large scale in Brazil. Methods: 8715 newborn blood samples were collected on filter paper and, after DNA elution, TRECs were quantified by real-time polymerase chain reaction. The cutoff value to determine whether a sample was abnormal was determined by ROC curve analysis, using SSPS. Results: The concentration of TRECs in 8,682 samples ranged from 2 to 2,181 TRECs/μL of blood, with mean and median of 324 and 259 TRECs/μL, respectively. Forty-nine (0.56% samples were below the cutoff (30 TRECs/μL and were reanalyzed. Four (0.05% samples had abnormal results (between 16 and 29 TRECs/μL. Samples from patients previously identified as having severe combined immunodeficiency or DiGeorge syndrome were used to validate the assay and all of them showed TRECs below the cutoff. Preterm infants had lower levels of TRECs than full-term neonates. The ROC curve showed a cutoff of 26 TRECs/μL, with 100% sensitivity for detecting severe combined immunodeficiency. Using this value, retest and referral rates were 0.43% (37 samples and 0.03% (3 samples, respectively. Conclusion: The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil. Resumo: Objetivo: aplicar no Brasil a técnica de quantificação de T-cell Receptor Excision Circles (TRECs por polymerase chain reaction em tempo real para triagem neonatal de imunodeficiência combinada grave (SCID e avaliar se é possível realizá-la em larga escala em nosso país. Métodos: foram coletadas 8.715 amostras de sangue de recém-nascidos em papel filtro e, após eluição do DNA, os TRECs foram quantificados por polymerase chain reaction em tempo real. O valor de corte para determinar se uma
Ingels, Helene; Schejbel, Lone; Lundstedt, A C
examined. RESULTS: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response......BACKGROUND: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory......-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. METHODS: Cases of rIPD in children 0-15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer...
Adenosine Deaminase Deficiency; Autosomal Recessive Disorder; Immune System Disorder; Purine-Nucleoside Phosphorylase Deficiency; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency With Absence of T and B Cells; X-Linked Severe Combined Immunodeficiency
M. van der Burg (Mirjam); A.R. Gennery (Andy R.)
textabstractSevere combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical
Sproston, Anthony R.M.; West, Catharine M.L.; Hendry, Jolyon H.
Purpose: The aim of the work was to establish to what extent a variety of human severe-combined-immunodeficiency (SCID) disorders are associated with in vitro cellular hypersensitivity to ionizing radiation. Materials and methods: A study was made of fibroblast strains established from individuals with adenosine deaminase deficiency, T(-)B(-) SCID, Omenn's syndrome and a SCID heterozygote. For comparison, an assessment was also made of the radiosensitivity of a series of fibroblast strains derived from: normal donors, a patient with ataxia-telangiectasia (A-T) and an A-T heterozygote. Radiosensitivity was determined using a clonogenic assay following both high (HDR) and low (LDR) dose-rate irradiation. Results: Following HDR irradiation, the fibroblast strains derived from the different human SCID disorders displayed a wide range of radiosensitivity: the adenosine deaminase deficiency cells were similar in radiosensitivity to normal fibroblasts, T(-)B(-) cells were as hypersensitive to radiation as A-T cells and the Omenn's syndrome cells showed intermediate radiosensitivity. However, whereas all four normal cell strains studied showed significant LDR sparing, none of the SCID fibroblasts did. Conclusions: These data indicate that human SCID is variable in terms of radiosensitivity depending on the particular defect. In addition, the lack of LDR sparing of radiation-induced damage suggests the involvement of some form(s) of DNA repair defect in all the human SCID syndromes
Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp
Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.
DeVoe, P W; Buckley, R H; Shirley, L R; Darby, C P; Ward, F E; Mickey, G H; Raab-Traub, N; Vandenbark, G R
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.
A.P.J. de Pagter (Anne); R.G.M. Bredius (Robbert); T.W. Kuijpers (Taco W.); J. Tramper (Jelco); M. van der Burg (Mirjam); J.M. van Montfrans (Joris); G.J.A. Driessen (Gertjan)
textabstractSevere combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment
de Pagter, Anne P. J.; Bredius, Robbert G. M.; Kuijpers, Taco W.; Tramper, Jelco; van der Burg, Mirjam; van Montfrans, JM; Driessen, Gertjan J.
Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The
de Pagter, Anne P. J.; Bredius, Robbert G. M.; Kuijpers, Taco W.; Tramper, Jelco; van der Burg, Mirjam; van Montfrans, Joris; Driessen, Gertjan J.; ten Berge, J. M. R.; Lambeck, A. J. A.; van de Corput, C. J. D.; Damoiseaux, J.; van Deuren, M.; van de Vosse, E.; Ellerbroek, P. M.; van Hagen, P. M.; van Leeuwen, E. M. M.; van den Berg, J. M.; Rutgers, B.; Scholvinck, L.; van Tol, M. J. D.; de Vries, E.; van Well, G.; de Leeuw, K.; van der Flier, M.; Roozendaal, C.
Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The
Pagter, A.P. de; Bredius, R.G.; Kuijpers, T.W.; Tramper, J.; Burg, M. van der; Montfrans, J. van; Driessen, G.J.; Flier, M. van der; et al.,
Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The
Miller, Holly K; Hanley, Patrick J; Lang, Haili; Lazarski, Christopher A; Chorvinsky, Elizabeth A; McCormack, Sarah; Roesch, Lauren; Albihani, Shuroug; Dean, Marcus; Hoq, Fahmida; Adams, Roberta H; Bollard, Catherine M; Keller, Michael D
Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
De Ranieri, Deirdre; Fenny, Nana Sarkoah
Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.
The authors have initiated studies designed to identify and characterize those parameters which must be considered in order to optimize immunoreconstitution following fetal tissue transplantation. The objectives of the first phase of experiments were to define ontogeny of lymphocyte function in equine fetal tissues and to determine if fetal liver and thymus, in combination, would immunologically reconstitute horses with combined immunodeficiency. (Auth.)
Baxter, K J; Levy, J K; Edinboro, C H; Vaden, S L; Tompkins, M B
Feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infection cause similar clinical syndromes of immune dysregulation, opportunistic infections, inflammatory diseases, and neoplasia. Renal disease is the 4th most common cause of death associated with HIV infection. To investigate the association between FIV infection and renal disease in cats. Client-owned cats (153 FIV-infected, 306 FIV-noninfected) and specific-pathogen-free (SPF) research colony cats (95 FIV-infected, 98 FIV-noninfected). A mixed retrospective/prospective cross-sectional study. Blood urea nitrogen (BUN), serum creatinine, urine specific gravity (USG), and urine protein:creatinine ratio (UPC) data were compared between FIV-infected and FIV-noninfected cats. In FIV-infected cats, total CD4+ and CD8+ T lymphocytes were measured using flow cytometry, and CD4+:CD8+ T lymphocyte ratio was calculated. Renal azotemia was defined as a serum creatinine ≥ 1.9 mg/dL with USG ≤ 1.035. Proteinuria was defined as a UPC > 0.4 with an inactive urine sediment. Among the client-owned cats, no association was detected between FIV infection and renal azotemia (P = .24); however, a greater proportion of FIV-infected cats were proteinuric (25.0%, 16 of 64 cats) compared to FIV-noninfected cats (10.3%, 20 of 195 cats) (P < .01). Neither neuter status nor health status were risk factors for proteinuria in FIV-infected cats, but UPC was positively correlated with the CD4+:CD8+ T lymphocyte ratio (Spearman's rho = 0.37, P = .01). Among the SPF research colony cats, no association was detected between FIV infection and renal azotemia (P = .21) or proteinuria (P = .25). Proteinuria but not azotemia was associated with natural FIV infection. Copyright © 2012 by the American College of Veterinary Internal Medicine.
Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A
Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Full Text Available Abstract Ataxia-telangiectasia (A-T is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T. A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.
Kuijpers, K. C.; van Dongen, J. J.; van der Burg, P.; Roos, M. T.; Vonk, J.; de Abreu, R.; de Korte, D.; van Noesel, C. J.; Weening, R. S.; van Lier, R. A.
The diagnosis severe combined immunodeficiency was made in a male infant at the age of 18 wk. Known causes of severe combined immunodeficiency were excluded. The activity of total 5'-nucleotidase (E.C. 220.127.116.11) in the PBMC was found to be strongly decreased. Analysis of the peripheral blood revealed
Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.
Stasenko, A A; Zhulaĭ, V V; Novopol'tseva, I Iu; Dontsova, L S; Zaiats, N V; Negievich, V I
There were examined 198 patients, in whom immunodeficient (inflammatory, infectious and viral) diseases were revealed, as well as 10 healthy persons--for investigation of sensitivity of the blood neutrophils to immunomodulators (timalin, immunofan, polyoxidonium, timogen, erbisol). Most active one, in accordance to the investigation data, have evolved a synthetic preparation polyoxidonium, action mechanism of which is caused by direct activating impact on phagocytosis. Absence of sensitivity of the blood neutrophils towards activating stimuli (immunomodulators) in some patients was caused by a phenomenon, according to which the blood neutrophils, persisting durably in a preactivated state, further (while examining of the patients) have a reduced capacity for answering to stimulation. Such factors, as persisting in organism components of cellular wall of microorganisms or viruses, as well as antiinflammatory citokines, which are secreted in answer to the infectious agent introduction, are altogether promote the blood neutrophils preactivated state persistence. In patients, suffering viral infections, the blood neutrophils are mostly sensitive to immunofan and timalin. Immunologic preparations must be selected individually, taking into account the data of tests for sensitivity.
Full Text Available Primary immunodeficiency diseases (PID are a heterogeneous group of disorders caused by inborn errors of immunity, with affected children presenting with severe, recurrent or unusual infections. Over 300 distinct genetic molecular abnormalities resulting in PID have been identified, and this number continues to rise. Newborn screening for PID has been established in many countries, with the majority of centers using a PCR-based T cell receptor excision circle (TREC assay to screen for severe combined immunodeficiency (SCID and other forms of T cell lymphopenia. Multiplexed screening including quantitation of kappa-recombining exclusion circles (KREC has also been described, offering advantages over TREC screening alone. Screening technologies are also expanding to include protein-based assays to identify complement deficiencies and granulocyte disorders. Given the rapid advances in genomic medicine, a potential future direction is the application of next-generation sequencing (NGS technologies to screen infants for a panel of genetic mutations, which would enable identification of a wide range of diseases. However, several ethical and economic issues must be considered before moving towards this screening strategy.
Full Text Available Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0 and three male IL2RG null (−/y F1 animals demonstrated severe combined immunodeficiency (SCID, characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by Bordetella bronchiseptica in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by Pneumocystis oryctolagi, as confirmed by histological examination and PCR analysis of Pneumocystis genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies.
Song, Jun; Wang, Guoshun; Hoenerhoff, Mark J.; Ruan, Jinxue; Yang, Dongshan; Zhang, Jifeng; Yang, Jibing; Lester, Patrick A.; Sigler, Robert; Bradley, Michael; Eckley, Samantha; Cornelius, Kelsey; Chen, Kong; Kolls, Jay K.; Peng, Li; Ma, Liang; Chen, Yuqing Eugene; Sun, Fei; Xu, Jie
Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (−/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by Bordetella bronchiseptica in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by Pneumocystis oryctolagi, as confirmed by histological examination and PCR analysis of Pneumocystis genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies. PMID:29593714
Abolhassani, Hassan; Chou, Janet; Bainter, Wayne; Platt, Craig D; Tavassoli, Mahmood; Momen, Tooba; Tavakol, Marzieh; Eslamian, Mohammad Hossein; Gharagozlou, Mohammad; Movahedi, Masoud; Ghadami, Mohsen; Hamidieh, Amir Ali; Azizi, Gholamreza; Yazdani, Reza; Afarideh, Mohsen; Ghajar, Alireza; Havaei, Arash; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Cheraghi, Taher; Behniafard, Nasrin; Amin, Reza; Aleyasin, Soheila; Faridhosseini, Reza; Jabbari-Azad, Farahzad; Nabavi, Mohammamd; Bemanian, Mohammad Hassan; Arshi, Saba; Molatefi, Rasol; Sherkat, Roya; Mansouri, Mahboubeh; Mesdaghi, Mehrnaz; Babaie, Delara; Mohammadzadeh, Iraj; Ghaffari, Javad; Shafiei, Alireza; Kalantari, Najmeddin; Ahanchian, Hamid; Khoshkhui, Maryam; Soheili, Habib; Dabbaghzadeh, Abbas; Shirkani, Afshin; Nasiri Kalmarzi, Rasoul; Mortazavi, Seyed Hamidreza; Tafaroji, Javad; Khalili, Abbas; Mohammadi, Javad; Negahdari, Babak; Joghataei, Mohammad-Taghi; Al-Ramadi, Basel K; Picard, Capucine; Parvaneh, Nima; Rezaei, Nima; Chatila, Talal A; Massaad, Michel J; Keles, Sevgi; Hammarström, Lennart; Geha, Raif S; Aghamohammadi, Asghar
Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.
Szczawinska‐Poplonyk, Aleksandra; Jonczyk‐Potoczna, Katarzyna; Breborowicz, Anna; Bartkowska‐Sniatkowska, Alicja; Figlerowicz, Magdalena
Please cite this paper as: Szczawinska‐Poplonyk et al. (2012) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12059. Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high‐risk patients with underlying conditions, particularl...
Raz Somech; Amos Etzioni
Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of co...
Claudia A Montiel-Equihua
Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial
Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo
Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Full Text Available Claire Booth1,2, H Bobby Gaspar1,21Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK; 2Dept of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UKAbstract: Adenosine deaminase deficiency (ADA is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID, a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT with pegademase bovine (PEG-ADA and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.Keywords: adenosine deaminase deficiency, PEG-ADA, enzyme replacement therapy, severe combined immune deficiency (SCID
Nguyen, Alexandre; Martin Silva, Nicolas; de Boysson, Hubert; Damaj, Gandhi; Aouba, Achille
Cartilage hair hypoplasia (CHH) is a rare autosomal recessive ribosomopathy characterised by skeletal and integumentary system manifestations. It may also present with varied forms and intensities of haematopoietic and/or immune disorders. We report a 27-year-old female who presented a picture of combined immunodeficiency after receiving an adriamycin-based chemotherapy regimen followed by autologous stem cell transplantation. Her medical history indicated neonatal dwarfism, recurrent ear, nose and throat and respiratory infections, and hypogammaglobulinaemia, which were suggestive of a primary minor B-cell immune deficiency. Taken together, the diagnosis of cartilage hair hypoplasia was suspected and confirmed by means of molecular biological analysis. Here, we discuss the causal relationship and molecular mechanisms existing between both primary immunodeficiency and lymphoma conditions and between chemotherapy cytotoxicity and aggravation of the immune system and associated hematopoietic dysfunction, considering the role of all these components in light of the initially undiagnosed cartilage hair hypoplasia. Finally, this case highlights the importance of screening for primary immunodeficiencies in the setting of a diagnosis of lymphoma and/or dwarfism; moreover, CHH must be distinguished from other causes of small size; its diagnosis and complete check-up must include the molecular characterisation, and its management must be global in collaboration with haematologists, immunologists and internists.
Hezaim, K.A.; Javed, F.; Askar, A.; Rasheed, A.A.
Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and inter dental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to identify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction. (author)
Parikh, Vishal S; Jagadeesh, Deepa; Fernandez, James M; Hsi, Eric D; Singh, Arun D
Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.
Akar, H. Haluk; Patiroglu, Turkan; Hershfield, Michael; van der Burg, Mirjam
Combined immunodeficiencies (CIDs) include a group of inherited monogenic disorders. CIDs are characterized by defective cellular and humoral immunities that lead to severe infections. CIDs can be classified according to immunologic phenotypes as T?B?NK? CID, T?B?NK+ CID, T?B+NK? CID and T?B+NK+ CID. In a 20-year period, from 1994 to 2014, a total of 40 CID patients were diagnosed at the Pediatric Immunology of Erciyes University Medical Faculty in Kayseri, Turkey. The gender ratio (F/M) was ...
Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko
Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.
Priya, D; Sudharshan, S; Biswas, Jyotirmay
Vogt-Koyanagi-Harada (VKH), a multisystem autoimmune bilateral panuveitis with systemic manifestations, is uncommon in immunocompromised patients such as human immunodeficiency virus (HIV)/acquired immunodeficiency disease syndrome (AIDS). We report a rare presentation of VKH in a 45-year-old HIV-positive female on highly active antiretroviral therapy (HAART) who presented with a history of recurrent panuveitis. A diagnosis of probable VKH was made based on ocular and systemic signs and symptoms. She was treated with topical and systemic steroids with close monitoring of CD4 counts and viral loads. After inflammation control, complicated cataract was managed surgically under perioperative steroid cover. VKH in HIV/AIDS has not been reported earlier. This case shows that significant inflammation can be seen even in HIV/AIDS patients on HAART with VKH in spite of moderate CD4 counts. Management is a challenge considering the systemic risks with long-term use of steroids.
Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte
Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy
Reichenbach, Janine; Schubert, Ralf; Horvàth, Rita; Petersen, Jens; Fütterer, Nancy; Malle, Elisabeth; Stumpf, Andreas; Gebhardt, Boris R; Koehl, Ulrike; Schraven, Burkhart; Zielen, Stefan
We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo-occipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes II+III and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8(+) T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8(+) T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease.
Andrea Z. Tuckett
Full Text Available Abstract Background Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Methods Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+ and injected intravenously or intrathymically into both male and female, young or aged NOD-scid IL2rγnull recipients. The in vivo fate of injected cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and spleen-derived T cell populations. In addition to T cell reconstitution, we evaluated mice for evidence of immune dysregulation based on diabetes development and graft-versus-host disease. T cell immunity following intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice was assessed in a B cell lymphoma model. Results Despite the small size of the thymic remnant in NOD-scid IL2rγnull mice, we were able to accomplish precise intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound-guided injection. Thymic reconstitution following intrathymic injection of healthy allogeneic hematopoietic cells was most effective in young male recipients, indicating that even in the setting of severe immunodeficiency, sex and age are important variables for thymic function. Allogeneic T cells generated in intrathymically injected NOD-scid IL2rγnull mice displayed anti-lymphoma activity in vivo, but we found no evidence for severe auto/alloreactivity in T cell-producing NOD-scid IL2rγnull mice, suggesting that immune dysregulation is not a major concern
White, Joanna; Stickney, Alison; Norris, Jacqueline M
Feline immunodeficiency virus (FIV) is an important infection in both domestic and nondomestic cats. Although many studies have provided insight into FIV pathophysiology and immunologic responses to infection in cats, questions remain regarding the association of FIV with specific disease syndromes. For many diseases, both association and causation of disease with FIV remain to be confirmed and clarified. The use of experimental infection models is unlikely to yield answers about naturally infected domestic cats and is not feasible in nondomestic felids, many of which are endangered species. Researches might consider further study of naturally occurring disease with an emphasis on confirming which diseases have a likely association with FIV.
Chang, Chun-Kai; Kao, Cheng-Feng; Lin, Pi-Han; Huang, Hui-Lin; Ho, Shu-Yuan; Wong, Kuo-Chen; Lin, Bo-Chang; Yeh, Chang-Ching; Lee, Chia-Yeh; Kao, Chuan-Liang; Lee, Chun-Nan; Chang, Sui-Yuan; Yang, Jyh-Yuan
The fourth-generation human immunodeficiency virus (HIV) combination assay, which can simultaneously detect the presence of anti-HIV antibody and HIV antigen, has been shown to shorten the window period in HIV diagnosis compared with the third-generation HIV antibody immunoassay. This study was aimed to determine the performance of HIV combination assays in Taiwan, where the HIV-1 seroprevalence is 0.007% and HIV-2 infection has never been reported. Performance of three fourth-generation HIV Ag/Ab combination assays (Dia.Pro, Wantai, and Bio-Rad) and one third-generation HIV Ab immunoassay (AxSYM HIV 1/2 gO) was assessed. A total of 152 specimens, including 86 confirmed HIV-seropositive and 66 HIV-seronegative samples, were used in the study. The sensitivity of four assays varied from 98.8% to 100%, and specificity varied from 98.5% to 100%. Performance of the 75 equivocal samples, the HIV status of which was confirmed later, in terms of negative prediction varied from 81.8% to 87.5%. The Bio-Rad and Dia.Pro assays exhibited higher sensitivity for the detection of p24 antigen among the three fourth-generation HIV combination assays. The three fourth-generation HIV Ag/Ab combination assays exhibited better sensitivity, specificity, and negative prediction than the third-generation HIV Ab immunoassay. Copyright © 2015. Published by Elsevier B.V.
Hosono, Makoto; Takaori-Kondo, Akifumi; Zheng-Sheng, Yao; Kobayashi, Hisataka; Hosono, Masako N.; Sakahara, Harumi; Imada, Kazunori; Okuma, Minoru; Uchiyama, Takashi; Konishi, Junji
Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered 125 I- and 111 In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using 111 In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL
Wu Jianqiu; Yang Yunfang; Jin Zhijun; Cai Jianming; Yang Rujun; Xiang Yingsong
Objective: To explore a new method for developing the efficiency of human umbilical cord blood (UCB) cells engraftment, and further understand the growth characteristic of hematopoietic stem cells (HSC) in vivo. Methods: Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted i.v. with UCB cells which had been cryo-preserved at -80 degree C. The human cells in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to the single transplantation, scheduled engraftment of similar numbers of UCB cells resulted in a proportionally obvious increase in the percentages of CD45 + , CD34 + cells produced in SCID mouse bone marrow (BM). When the donor cells were reduced to 20 percent, an identical reconstitution of both hematopoietic and part of immunologic functions was achieved. Conclusion: Scheduled engraftment improves the repopulating ability of HSC, which would provide a novel way for clinical cord blood engraftment in adult objects
Full Text Available Primary immunodeficiency disorders (PIDs render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG vaccination and dissemination in combined immunodeficiencies. Varied phenotype expression poses a challenge to identification of the putative immune deficit. Without the availability of genomic diagnosis and data analysis resources and with limited capacity for functional definition of immune pathways, it is difficult to establish a definitive diagnosis and to decide on appropriate treatment. This study describes the use of exome sequencing to identify a homozygous recessive variant in MAP3K14, NIKVal345Met, in a patient with combined immunodeficiency, disseminated BCG-osis, and paradoxically elevated lymphocytes. Laboratory testing confirmed hypogammaglobulinemia with normal CD19, but failed to confirm a definitive diagnosis for targeted treatment decisions. NIKVal345Met is predicted to be deleterious and pathogenic by two in silico prediction tools and is situated in a gene crucial for effective functioning of the non-canonical nuclear factor-kappa B signaling pathway. Functional analysis of NIKVal345Met- versus NIKWT-transfected human embryonic kidney-293T cells showed that this mutation significantly affects the kinase activity of NIK leading to decreased levels of phosphorylated IkappaB kinase-alpha (IKKα, the target of NIK. BCG-stimulated RAW264.7 cells transfected with NIKVal345Met also presented with reduced levels of phosphorylated IKKα, significantly increased p100 levels and significantly decreased p52 levels compared to cells transfected
Burton, Janet; Murphy, Elyse; Riley, Patty
Patient-centered chronic care management is a new model for the management of rare chronic diseases such as primary immunodeficiency disease (PIDD). This approach emphasizes helping patients become experts on the management of their disease as informed, involved, and interactive partners in healthcare decisions with providers. Because only a few patients are affected by rare illnesses, these patients are forced to become knowledgeable about their disease and therapies and to seek treatment from a healthcare team, which includes physicians and nurse specialists who are equipped to manage the complexity of the disease and its comorbidities. Importantly, therapy for PIDD can be self-administered at home, which has encouraged the transition toward a proactive stance that is at the heart of patient-centered chronic care management. We discuss the evolution of therapy, the issues with the disease, and challenges with its management within the framework of other chronic disease management programs. Suggestions and rationale to move case management of PIDD forward are presented with the intent that sharing our experiences will improve process and better manage outcomes in this patient population. The patient-centered model for the management of PIDD is applicable to the primary care settings, where nurse case managers assist patients through education, support them and their families, and facilitate access to community resources in an approach, which has been described as "guided care." The model also applies specifically to immunology centers where patients receive treatment or instruction on its self-administration at home. Patient-centered management of PIDD, with its emphasis on full involvement of patients in their treatment, has the potential to improve compliance with treatment, and thus patient outcomes, as well as patients' quality of life. The patient-centered model expands the traditional model of chronic disease management, which relies on evidence
Sillevis Smitt, J. H.; Weening, R. S.; Krieg, S. R.; Bos, J. D.
We report the case of a boy with severe combined immunodeficiency (SCID) and serious skin problems. The level of purine 5'-nucleotidase was greatly reduced in the lymphocytes of this patient. To our knowledge, no patients with SCID and this enzyme deficiency have been described previously. The
ten Berge, R. J.; Schellekens, P. T.; Budding-Koppenol, A.; Dooren, L. J.; Vossen, J. M.
Natural killer-cell activity for K562 target cells was measured in 13 patients with severe combined immunodeficiency before bone marrow transplantation. Both unseparated peripheral blood mononuclear cells and sorted cell subsets (B73.1 positive, B73.1 negative, OKT3 positive, OKT3 negative) were
Schuurman, R.K.B.; Rood, J.J. van; Vossen, J.M.; Schellekens, P.Th.A.; Feltkamp-Vroom, Th.M.; Doyer, E.; Gmelig Meyling, F.H.J.; Visser, H.K.A.
A diagnosis of partial combined immunodeficiency was made in two Turkish siblings with a history of multiple pyogenic infections and persistent candidiasis. They demonstrated severe hypo-γ-globulinemia, with B-lymphocytes, but deficient plasma cell differentiation. T-Lymphocytes were decreased in
Borghans, José A.; Bredius, Robbert G.; Hazenberg, Mette D.; Roelofs, Helene; Jol-van der Zijde, Els C.; Heidt, Jeroen; Otto, Sigrid A.; Kuijpers, Taco W.; Fibbe, Willem E.; Vossen, Jaak M.; Miedema, Frank; van Tol, Maarten J.
The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT). It was suggested, however, that accelerated loss of thymus output may cause impaired immune function at the long
You, Yong Sung; Lee, Sung Jin; Lee, Sung Ho; Park, Chang Hyun
Purpose To describe an unusual case of rapidly progressive outer retinal necrosis (PORN) with vitreous hemorrhage in a 41-year-old woman with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from what was probably varicellar-zoster virus combined with cytomegalovirus (CMV) and herpes simplex type 1,2, as proven by the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Methods This study is a case report detailing clinical follow-up and an aqueous humor test by PCR-RFLP. Results The deep, white retinal lesions coalesced and progressively expanded in a circumferential manner, with sparing of the perivascular retina. However, retinal and vitreous hemorrhages, unusual findings for PORN, could be noted around the optic nerve. Varicellar-zoster virus (VZV), cytomegalovirus (CMV), and herpes simplex types 1,2 (HSV-1,2) were detected in the aqueous humor by PCR. Conclusions PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, concurrent or combined etiologic agents can include HSV-1, HSV-2, and CMV in AIDS patients. Therefore, combined antiviral therapy with acyclovir and ganciclovir could be more reasonable as an initial therapy. PMID:17460434
Vilela, Felippe Dantas; Lorenzo, Andrea Rocha de; Tura, Bernardo Rangel; Ferraiuoli, Giovanna Ianini; Hadlich, Marcelo; Barros, Marcelo Viana de Lima; Lima, Ana Beatriz Ribeiro; Meirelles, Vanderson
Current treatment for human immunodeficiency virus (HIV) infection has improved survival and allowed infected patients to develop atherosclerotic coronary artery disease (CAD). Specific strategies to reduce cardiovascular risk in the infected population have not been developed. It is necessary to know the magnitude of cardiovascular risk in this population. OBJECTIVES: This study aimed to assess cardiovascular risk using a well-known clinical score and to investigate coronary artery calcium s...
Tsabedze, Nqoba; Vachiat, Ahmed; Zachariah, Don; Manga, Pravin
The human immunodeficiency virus epidemic is a major health challenge of the twenty-first century as the transition from infectious complications to noncommunicable disease becomes more evident. These patients may present to the emergency department with a variety of cardiovascular diseases, such as acute coronary syndromes, heart failure, pericardial disease, infective endocarditis, venothromboembolism, and other conditions. Increased awareness is needed among health care professionals to enhance adequate identification and promote prompt management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.
Marciano, Beatriz E; Huang, Chiung-Yu; Joshi, Gyan; Rezaei, Nima; Carvalho, Beatriz Costa; Allwood, Zoe; Ikinciogullari, Aydan; Reda, Shereen M; Gennery, Andrew; Thon, Vojtech; Espinosa-Rosales, Francisco; Al-Herz, Waleed; Porras, Oscar; Shcherbina, Anna; Szaflarska, Anna; Kiliç, Şebnem; Franco, Jose L; Gómez Raccio, Andrea C; Roxo, Persio; Esteves, Isabel; Galal, Nermeen; Grumach, Anete Sevciovic; Al-Tamemi, Salem; Yildiran, Alisan; Orellana, Julio C; Yamada, Masafumi; Morio, Tomohiro; Liberatore, Diana; Ohtsuka, Yoshitoshi; Lau, Yu-Lung; Nishikomori, Ryuta; Torres-Lozano, Carlos; Mazzucchelli, Juliana T L; Vilela, Maria M S; Tavares, Fabiola S; Cunha, Luciana; Pinto, Jorge A; Espinosa-Padilla, Sara E; Hernandez-Nieto, Leticia; Elfeky, Reem A; Ariga, Tadashi; Toshio, Heike; Dogu, Figen; Cipe, Funda; Formankova, Renata; Nuñez-Nuñez, M Enriqueta; Bezrodnik, Liliana; Marques, Jose Gonçalo; Pereira, María I; Listello, Viviana; Slatter, Mary A; Nademi, Zohreh; Kowalczyk, Danuta; Fleisher, Thomas A; Davies, Graham; Neven, Bénédicte; Rosenzweig, Sergio D
Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications. Published by Mosby, Inc.
Liu, Chang; Duffy, Brian; Bednarski, Jeffrey J; Calhoun, Cecelia; Lay, Lindsay; Rundblad, Barrett; Payton, Jacqueline E; Mohanakumar, Thalachallour
To report the laboratory investigation of a case of severe combined immunodeficiency (SCID) with maternal T-cell engraftment, focusing on the interference of human leukocyte antigen (HLA) typing by blood chimerism. HLA typing was performed with three different methods, including sequence-specific primer (SSP), sequence-specific oligonucleotide, and Sanger sequencing on peripheral blood leukocytes and buccal cells, from a 3-month-old boy and peripheral blood leukocytes from his parents. Short tandem repeat (STR) testing was performed in parallel. HLA typing of the patient's peripheral blood leukocytes using the SSP method demonstrated three different alleles for each of the HLA-B and HLA-C loci, with both maternal alleles present at each locus. Typing results from the patient's buccal cells showed a normal pattern of inheritance for paternal and maternal haplotypes. STR enrichment testing of the patient's CD3+ T lymphocytes and CD15+ myeloid cells confirmed maternal T-cell engraftment, while the myeloid cell profile matched the patient's buccal cells. Maternal T-cell engraftment may interfere with HLA typing in patients with SCID. Selection of the appropriate typing methods and specimens is critical for accurate HLA typing and immunologic assessment before allogeneic hematopoietic stem cell transplantation. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: email@example.com.
Mary T. Bausch-Jurken
Full Text Available Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay. The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.
Booth, Claire; Gaspar, H Bobby
Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.
Valerio, D; Dekker, B M; Duyvesteyn, M G; van der Voorn, L; Berkvens, T M; van Ormondt, H; van der Eb, A J
We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA-SCID patient. In addition, wild-type sequences could be ...
Parvaneh, Nima; Filipovich, Alexandra H; Borkhardt, Arndt
Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, maintains lifelong subclinical persistent infections in humans. In the circulation, EBV primarily infects the B cells, and protective immunity is mediated by EBV-specific cytotoxic T cells (CTLs) and natural killer (NK) cells. However, EBV has been linked to several devastating diseases, such as haemophagocytic lymphohistiocytosis (HLH) and lymphoproliferative diseases in the immunocompromised host. Some types of primary immunodeficiencies (PIDs) are characterized by the development of EBV-associated complications as their predominant clinical feature. The study of such genetic diseases presents an ideal opportunity for a better understanding of the biology of the immune responses against EBV. Here, we summarize the range of PIDs that are predisposed to EBV-associated haematological diseases, describing their clinical picture and pathogenetic mechanisms. © 2013 John Wiley & Sons Ltd.
Kalina Warren V
Full Text Available Abstract The filoviruses, Ebola (EBOV and Marburg (MARV, cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult. Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies.
Higuchi, Shigenori; Yanabe, Yasuhide; Tsuchiya, Hiroyuki; Akahoshi, Izumi; Migita, Masahiro; Matsuda, Ichiro; Udaka, Keiji.
A 6 month old boy was diagnosed as a case of combined immunodeficiency (with predominant T cell defect by previous classification). His T cell count was decreased, his B cell count in peripheral blood was increased, his serum IgG level was decreased, his serum IgM level was normal and the thymus was not evident on CT scans and magnetic resonance imaging. Administration of the thymus hormone, thymosin, led to a partial recovery of T cell function without normalization of the T cell count. At age 26 months the patient received an irradiated thymus transplantation from a 16 week old female fetus. After the transplantation, the T cell count (mainly CD4 + cells) increased by 50-70%. A mild graft-versus-host reaction (GVHR) occurred and several immunosuppressants were prescribed. Chromosome analysis showed that the T cells have both 46 XY and 46 XX karyotypes while the B cells have the 46 XY karyotype alone. His cellular immunity (skin tests, DNA synthesis, mixed lymphocyte reaction, cytotoxic activity and natural killer cell function) and his serum IgG level remained low. However, being on regular γ-globulin therapy and oral anti-fungal drugs, he is now living normally with almost no trouble at age 6 years and 3 months. This case showed that irradiated thymus transplantation might be a useful method when an adequate donor for bone marrow transplantation is not available. The unexpected observation that the increased T cells were mainly CD4 may be related to the mild GVHR and the clinical improvement. (author)
Simon Lam; Fotini D Kavadas; Seemab Haider; Mary E Noseworthy
Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children
Vianed Marsán Suárez
presented in this paper. The echographic test indicated tymus hypoplasia. There were reduced numbers of TCD4+, CD8+ lymphocytes and of natural killer cells. The lymphocyte B count was normal. Normal concentrations of serum IgM and IgG immunoglobulins as well as decreased concentrations of IgA were found. The total hemolytic activity of the classical complement pathway declined. No alteration was found in the opsonocytophagic function. The diagnosis was associated combined immunodeficiency, which proved the heterogeneity of the clinical expression of Edwards' syndrome and the relationship between the chromosomal defect and the formation of immune system in the intrauterine period.
Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella
Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the
Full Text Available Primary immunodeficiencies are clinically and epidemiologically important, despite their low prevalence, due to the associated risk of high morbidity and mortality. Most commonly encountered primary immunodeficiencies include humoral immune system deficiencies, cellular immune system defects, combined immunodeficiencies, phagocyte system defects, complement system defects. Classical clinical findings of immunodeficiencies include recurrent, severe infections which do not respond to treatment or which progress with complications as well as tendency to develop infections with low virulence microorganisms. Moreover, they may present with autoimmunity, autoinflammatory or hemaphagocytic syndromes. Congenital diseases usually start in early childhood and lead to morbidity and mortality. Therefore, early diagnosis may be life saving and allow increasing quality of life, genetic counseling or prenatal diagnosis. Considering primary immunodeficiencies more frequently in differential diagnosis and early immunological evaluation would lead to early diagnosis of these patients and allow them to reach early treatment or preventive measures.
Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp
Background Uncertainty about factors influencing the susceptibility and triggers for Graves’ disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Main text Relevant studies were identified through a systematic literature search using the P...
Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.
IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in
Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J
Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have
Full Text Available Human immunodeficiency virus type I (HIV-1 infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.
Cavarelli, Mariangela; Scarlatti, Gabriella
Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.
Jolles, S.; Sánchez-Ramón, S.; Quinti, I.; Soler-Palacín, P.; Agostini, C.; Florkin, B.; Couderc, L.J.; Brodszki, N.; Jones, A.; Longhurst, H.; Warnatz, K.; Haerynck, F.; Matucci, A.; de Vries, E.
Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres
Ayokunle, Dada Samuel; Olusegun, Olanrewaju Timothy; Ademola, Aderibigbe; Adindu, Chijioke; Olaitan, Rafiu Mojeed; Oladimeji, Ajayi Akande
Human immunodeficiency virus (HIV) the causative agent of Acquired immunodeficiency syndrome (AIDS) is an important cause of renal diseases in sub-Saharan Africa. There is paucity of studies on the burden of chronic kidney disease (CKD) among patients with HIV/AIDS in the North-Central zone of Nigeria. This is a cross-sectional study of 227 newly-diagnosed, antiretroviral naïve patients with HIV/AIDS seen at the HIV clinic of the Medical Out-patient Department (MOPD) of University of Ilorin Teaching Hospital (UITH). They were matched with 108 control group. Laboratory investigations were performed for the participants. CKD was defined as estimated glomerular filtration rate (eGFR) 30 mg/g. There were 100 (44%) males among the patients and 47 (43.5%) among the control group. The mean ages of the patients and controls were 40.3 ± 10.3 years and 41.8 ± 9.5 years respectively. CKD was observed in 108 (47.6%) among the patients and 18 (16.7%) of the controls (p = 0.01). The median CD4 T-cell count was significantly lower in patients with CKD. Ninety-three (41.0%) of the patients had dipstick proteinuria of > 2 +. The median albumin creatinine ratio (ACR) was significantly higher among the HIV-positive patients (272.3 mg/g) compared with the HIV-negative controls (27.22 mg/g) p = 0.01. The CD4 T-cell count correlates positively with eGFR (r = 0.463, p = 0.001) and negatively with ACR (r = -0.806, p = 0.001). CKD is very common among patients with HIV/AIDS in Ilorin. Screening and early intervention for CKD should be part of the protocols in the management of these patients.
Folgori, Laura; Scarselli, Alessia; Angelino, Giulia; Ferrari, Francesca; Antoccia, Antonio; Chessa, Luciana; Finocchi, Andrea
Abstract Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively wi...
Valencia Ortega, M E
Since the start of the human immunodeficiency virus (HIV) epidemic, tumour disease among patients has been significant. The collection of malignancies can be divided primarily into 2 groups: those associated with HIV (all of which are related to viral diseases) and those not associated with HIV (only some of which are associated with viral diseases). The origin of these malignancies is multifactorial, and the main causes that have led to an increase in tumour disease are immunosuppression, coinfection with oncogenic viruses and life prolongation secondary to the use of antiretroviral therapy. Establishing the general characteristics of the undiagnosed AIDS tumours is difficult, mainly because they are a highly heterogeneous group formed by malignancies of a diverse nature. The treatments do not differ from those used in the general population, although the management can be more difficult due to the late diagnosis, drug interactions and associated comorbidities. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J
Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.
Alvarez-Cardona, Aristoteles; Espinosa-Padilla, Sara Elva; Reyes, Saul Oswaldo Lugo; Ventura-Juarez, Javier; Lopez-Valdez, Jaime Asael; Martínez-Medina, Lucila; Santillan-Artolozaga, Alberto; Cajero-Avelar, Adriana; De Luna-Sosa, Alma R; Torres-Bernal, Luis F; Espinosa-Rosales, Francisco J
Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders characterized mainly by recurrent infections. Late diagnosis remains as one of the main issues to solve. We aimed to increase PID diagnosis in Aguascalientes, a 1.3 million inhabitants state in the center of Mexico, and to describe the clinical features of such patients. We developed an educational program for health personnel and general public; patients with possible PID were referred to a State University clinical center from December 2011 to December 2012. The patients were evaluated at the clinic and their definitive diagnosis pursued through laboratory, molecular and genetic assays. We describe the findings of those patients and analyze the impact of the program in terms of number of referrals. After 41 talks and 12 media appearances 151 patients were referred for evaluation. Fifteen (9.9%) were diagnosed with PID: five (33%) had antibody deficiencies, seven (47%) Well-defined syndromes, two (13%) Severe combined Immunodeficiency (SCID) and one case (7%) of an innate immune deficiency. All of the 15 PID patients had been referred by physicians, as opposed to the public. We estimated a "number needed to teach" of 75 physicians to get one PID patient referral. Educational programs are a fundamental part of the global efforts to increase PID diagnosis and care. To be successful, such programs should include public relations, reach for first-contact physicians, and aim to develop an efficient referral network with molecular diagnostic capability. Enhancing medical knowledge on PID is a successful strategy to improve early diagnosis and treatment.
Zhu Ying; Zhang Zhiyong; Shi Yuxin; Feng Feng
Objective: To study the CT features of pulmonary non-tuberculous mycobacteria (NTM) disease in patients with acquired immunodeficiency syndrome (AIDS) and explore the different CT appearances between AIDS-NTM and AIDS-TB. Methods: CT findings of pulmonary NTM disease in 27 AIDS patients (NTM group) were retrospectively analyzed and compared with that of tuberculosis in 30 AIDS patients (TB group). The results were statistically analyzed using Fisher's exact test. Results: CT findings of NTM appeared significantly more than that of TB as follows: high-density nodules (n = 18 vs 1, P < 0.01), ground-glass opacities (n = 10 vs 0, P < 0.01), fibrotic band (n = 17 vs 3, P < 0.01), bronchiectasis (9 vs 2, P = 0.012). CT findings of NTM appeared significantly less than that of TB as follows: miliary nodules (0 vs 6, P = 0.016), air space consolidations (n = 2 vs 11, P < 0.01), pleural effusion (n = 1 vs 9, P < 0.01). Conclusion: Nodule and fibrotic band accompanied with bronchiectasis were the main CT manifestations of pulmonary NTM disease in AIDS patients, while air space consolidation accompanied with pleural effusion and miliary nodules were the predominate CT findings of pulmonary tuberculosis in AIDS patients. (authors)
Kuijpers, Taco W.; van Leeuwen, Ester M. M.; Barendregt, Barbara H.; Klarenbeek, Paul; Aan de Kerk, Daan J.; Baars, Paul A.; Jansen, Machiel H.; de Vries, Niek; van Lier, René A. W.; van der Burg, Mirjam
Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined
Watkinson Sally J
Full Text Available Abstract Introduction If left untreated, severe combined immunodeficiency can lead to an acute susceptibility to infection. The intrauterine environment is sterile until the amniotic membranes rupture. The vaginal flora then ascends into the genital tract, thus increasing the risk of chorioamnionitis. An extremely premature and prolonged membrane rupture is associated with a dismal prognosis for an immunocompetent preterm fetus. There are no case reports to date that detail the outcome of an immunocompromised preterm baby following prolonged rupture of membranes. Case presentation We present the case of a 32-year-old Indian woman who delivered a 31-week gestational baby who had a severe combined immunodeficiency following premature prelabour prolonged rupture of the membranes at the 14th week of gestation. Conclusion Extreme preterm prelabour spontaneous rupture of membranes in an underlying condition of severe combined immunodeficiency does not necessarily lead to an unfavourable outcome.
Prakash, J; Ganiger, V; Prakash, S; Sivasankar, M; Sunder, S; Singh, U
Human immunodeficiency virus (HIV) infection can cause a broad spectrum of renal diseases. However, there is paucity of Indian data on the patterns of renal lesions in HIV-seropositive patients. The aim of the present study was to delineate the spectrum of renal lesions in HIV/acquired immunodeficiency syndrome patients. In this prospective study, all HIV-positive patients of both genders aged >18 years were screened for renal disease. Patients with proteinuria of more than 1 g/24 h were subjected to renal biopsy. A total of 293 HIV-positive patients were screened; of these, 136 (46.4%) patients found to have renal involvement. Dipstick-positive proteinuria of 1+ or more was observed in 112 (38.2%) patients, and 16 (14.2%) patients had proteinuria of more than 1 g/24 h. Renal biopsy in 14 cases revealed glomerulonephritis (GN) in 12 (85.7%) (isolated GN in 4 [28.5%] and GN mixed with chronic TIN in 8 [57.1%]) patients. These include mesangioproliferative GN in 5 (35.7%), membranoproliferative GN in 2 (14.2%), focal segmental glomerulosclerosis in 2 (14.2%), diffuse proliferative GN in 2 (14.2%), and diabetic nephropathy in 1 (7.1%) patients. Chronic interstitial nephritis was noted in 10 (71.42%) (superimposed on GN in 8 [57.1%], isolated in 2 [14.2%]) patients. Granulomatous interstitial nephritis was seen in 3 (24.1%) cases. GN and chronic interstitial nephritis were noted in 85.7% and 71.42% of patients, respectively, mostly superimposed on each other. Mesangioproliferative GN was the most common glomerular lesion, but classical HIV-associated nephropathy was not observed.
Martínez, Esteban; Jódar Gimeno, Esteban; Reyes García, Rebeca; Carpintero, Pedro; Casado, José Luis; Del Pino Montes, Javier; Domingo Pedrol, Pere; Estrada, Vicente; Maalouf, Jorge; Negredo, Eugenia; Ocampo, Antonio; Muñoz-Torres, Manuel
To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon
The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in
Pierce, G.F.; Polmar, S.H.; Schacter, B.Z.; Brovall, C.; Hornick, D.L.; Sorensen, R.U.
We studied spontaneous natural killer (NK) cell activity and radiation-resistant NK mediated cytotoxicity in four patients with clinically documented severe combined immune deficiency disease (SCID), and in one subject each with intestinal lymphangiectasia and cartilage-hair hypoplasia. We observed the preservation of spontaneous NK activity in all patients despite the presence of profound B- and T-lymphocytopenia and clinical immunodeficiency. NK activity was associated with relatively normal circulating numbers of OKM1+ lymphocytes, a population known to contain NK effectors. Spontaneous NK activity resistant to 3000 rad was increased in all patients, indicating the presence of activated natural killer cells in vivo. The concept of a chronically activated immune system in these patients was further supported by the presence of increased Ia positive T cells in all subjects tested, suggesting that radioresistant NK activity may be a useful parameter to measure when assessing in vivo immune activation. Our data, as well as that of others, supports the hypothesis that at least one population of NK cells is a distinct lineage arising at the differentiation level of myeloid and lymphoid stem cells in the bone marrow
Full Text Available A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.
Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H
Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA. © Georg Thieme Verlag KG Stuttgart · New York.
Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.
Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A
For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and
Full Text Available Children with primary Tslymphocyte deficiency arc more ."I/."'clptihfe to infection hy organisms such (15: bacteria, fungi. prolo:o(J lind virus, 1711.' isniatian oj all opponuniuic ory;ani."m or an IImallally severe infection with higher grade pathogens, provide a clue (0 diagnosis of immunodeficiency, To determine the microorganisms causing recurrent or severe infections in children with T•(rmpllOcy!e doflcicncy, we carried out II retrospective case review oj H5 patients with 1'../ympllOC'te deficiency who wuc investigated at the Great Ormond Street Hospital for Children, NHS Trust, OH'r the 5 year period between June I, 1188 and June I, 1193. Tuc /:mllp of patients included 53 mules anti 32 [cmales, among which 23 and 62 were diagnosed to prewnt SClf (/",1 elf subtypes respectively, Among the 174 organisms isolated. these included bacteria (97 isolates], viruses (43 isolates}, funJ:i (25 isolates] and parasites (9 isolates}, 17lC predominant ."ites of infections were mainly the gll. rointe. itwl (60 out of 174 and respiratory tracts (49 out of 174. 171£' most common bacterial infections, were with aerobic gram negative organisms (28 isolatcs, P.H'UdOmOnllS aeruginosa (17 isolates], Enterococcus (/2 isolates, C. difficile (10 isolates], Analysis: of 43 viral infection showed that Homvirus (10 isolates], Adenovirus (9 isolates], Herpes simplex (6 isolates], am!"nC}loml'!:altH'iTlH (6 isalatcs, Wi'rl! prrdominutu pathogens. Candida albicans was IIII' most commonly isolated fungi. Parasitic infections included P. curini and Cryp(o."poridillm, 3 and (j opt of 9 cases. In our }iTOUp of pmients 16 patients' died before hone maTOOW transplantation, due to infectimu complication. Based on this . lldy. we ,wgge.lt thai pronytaxis aJjllin.rt bacterial, viral, Jllngal ami protozoa agents is a necessity to minimize infectious complication." in 7~/ympilOcyte deficient patients, awaiting a hone
Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.
Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro
Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.
de Saint Basile, G.; Arveiler, B.; Oberle, I.
The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis
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Zh. Z. Trumova
Full Text Available The human immunodeficiency virus (HIV epidemic continues to expand in Eastern Europe and Central Asia according to UNAIDS data (2012, Geneva. The rate of new HIV infections AIDS – related mortality has increased by 25 % from 2001 to 2009 in Kazakhstan (WHO data, 2012. The number of new HIV infections among newly diagnosed patients attributed to heteroand homosexual contact has been steadily increasing. There is also higher rate of HIV among Injecting Drug Users. There is an increase incidence of co-infections especially sexually transmitted diseases. In fact, comorbid STIs increase patients' susceptibility of acquiring and transmitting HIV (Guenthner PC, Secor WE, Dezzutti CS., 2005; Kissinger P, Amedee A, Clark RA, et al. , 2009. HIV/AIDS shares transmission characteristics with other sexual and blood-borne agents. Higher sexual mixing rates and lack of condom use are conspicuous risk factors (Vermund et al. 2009. However, while all groups are affected by HIV, some are more vulnerable than others: sex workers (SWs, men who have sex with men (MSM, injecting drug users (IDU. All these findings determined to set up the goal of this research. The purpose of the study is еpidemiologic situation of human immunodeficiency virus (HIV/AIDS and related STIs in the Republic of Kazakhstan and in some vulnerable population groups to HIV infection. Materials and methods. To study the dynamics of HIV/STIs in Kazakhstan (cumulatively an analysis of 2012–2013 years statistics was conducted. Testing for HIV/STI of blood samples of the vulnerable groups was carried out in the laboratories of AIDS centers. The algorithm of confirming the diagnosis of HIV infection included a twofold enzyme immunoassay (EIA study of blood samples. Samples with positive results of the first EIA were retested using expert test systems; in case with a positive result of the second EIA a confirmatory test was conducted using a method of HIV-1 Western blot in the reference
Ellis J. Powell
Full Text Available After the discovery of naturally occurring severe combined immunodeficiency (SCID within a selection line of pigs at Iowa State University, we found two causative mutations in the Artemis gene: haplotype 12 (ART12 and haplotype 16 (ART16. Bone marrow transplants (BMTs were performed to create genetically SCID and phenotypically immunocompetent breeding animals to establish a SCID colony for further characterization and research utilization. Of nine original BMT transfer recipients, only four achieved successful engraftment. At approximately 11 months of age, both animals homozygous for the ART16 mutation were diagnosed with T cell lymphoma. One of these ART16/ART16 recipients was a male who received a transplant from a female sibling; the tumors in this recipient consist primarily of Y chromosome-positive cells. The other ART16/ART16 animal also presented with leukemia in addition to T cell lymphoma, while one of the ART12/ART16 compound heterozygote recipients presented with a nephroblastoma at a similar age. Human Artemis SCID patients have reported cases of lymphoma associated with a “leaky” Artemis phenotype. The naturally occurring Artemis SCID pig offers a large animal model more similar to human SCID patients and may offer a naturally occurring cancer model and provides a valuable platform for therapy development.
Vilela, Felippe Dantas; Lorenzo, Andrea Rocha de; Tura, Bernardo Rangel; Ferraiuoli, Giovanna Ianini; Hadlich, Marcelo; Barros, Marcelo Viana de Lima; Lima, Ana Beatriz Ribeiro; Meirelles, Vanderson
Current treatment for human immunodeficiency virus (HIV) infection has improved survival and allowed infected patients to develop atherosclerotic coronary artery disease (CAD). Specific strategies to reduce cardiovascular risk in the infected population have not been developed. It is necessary to know the magnitude of cardiovascular risk in this population. This study aimed to assess cardiovascular risk using a well-known clinical score and to investigate coronary artery calcium scoring (CACS) in this population. This was a cross-sectional study. Adults with HIV infection were studied. Demographic, clinical and anthropometric data, serum glucose and lipids were obtained. Cardiovascular risk was calculated through Framingham risk score (FRS) and CACS. Categorical variables were compared by Chi-square or Fisher's exact test, and continuous variables were analyzed by Student t test or Mann-Whitney test. An analysis of concordance between FRS and CACS was performed using kappa statistic. Forty patients, aged 45.9 ± 8.1 years, were studied. Age of risk for CAD were found in 30.0%, hypertension in 55.0%, diabetes in 10.0%, smoking in 35.0%, dyslipidemia in 67.5% and family history of CAD in 57.5%. Altered levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were found in 30.0%, 25.0% and 82.5%, respectively. HDL-cholesterol and triglycerides were altered more frequently among protease inhibitors users. The FRS classified the risk as low for 72.5%, moderate for 25.0%, and high for 2.5%. CACS > 0 was found in 32.5% of the patients, in 67.5% the score was low, in 17.5% moderate, and in 15.0% high. Concordance between FRS and CACS showed a kappa = 0.435. There is a high prevalence of risk factors for CAD in the studied population, with dyslipidemia being the most frequent. HDL-cholesterol and triglycerides were the most frequently altered factors and were associated with the use of protease inhibitors. Risk assessed by the FRS was low in most
Felippe Dantas Vilela
Full Text Available Current treatment for human immunodeficiency virus (HIV infection has improved survival and allowed infected patients to develop atherosclerotic coronary artery disease (CAD. Specific strategies to reduce cardiovascular risk in the infected population have not been developed. It is necessary to know the magnitude of cardiovascular risk in this population. OBJECTIVES: This study aimed to assess cardiovascular risk using a well-known clinical score and to investigate coronary artery calcium scoring (CACS in this population. METHODS: This was a cross-sectional study. Adults with HIV infection were studied. Demographic, clinical and anthropometric data, serum glucose and lipids were obtained. Cardiovascular risk was calculated through Framingham risk score (FRS and CACS. Categorical variables were compared by Chi-square or Fisher's exact test, and continuous variables were analyzed by Student t test or Mann-Whitney test. An analysis of concordance between FRS and CACS was performed using kappa statistic. RESULTS: Forty patients, aged 45.9 ± 8.1 years, were studied. Age of risk for CAD were found in 30.0%, hypertension in 55.0%, diabetes in 10.0%, smoking in 35.0%, dyslipidemia in 67.5% and family history of CAD in 57.5%. Altered levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were found in 30.0%, 25.0% and 82.5%, respectively. HDL-cholesterol and triglycerides were altered more frequently among protease inhibitors users. The FRS classified the risk as low for 72.5%, moderate for 25.0%, and high for 2.5%. CACS > 0 was found in 32.5% of the patients, in 67.5% the score was low, in 17.5% moderate, and in 15.0% high. Concordance between FRS and CACS showed a kappa = 0.435. CONCLUSIONS: There is a high prevalence of risk factors for CAD in the studied population, with dyslipidemia being the most frequent. HDL-cholesterol and triglycerides were the most frequently altered factors and were associated with the use of
Birriel, J A; Adams, J A; Saldana, M A; Mavunda, K; Goldfinger, S; Vernon, D; Holzman, B; McKey, R M
Flexible fiberoptic bronchoscopy with bronchoalveolar lavage was performed in 16 pediatric patients with the acquired immunodeficiency syndrome (AIDS) and deterioration in pulmonary function suggestive of opportunistic infection. In 62% of the patients Pneumocystis carinii was identified. Culture results showed a pure growth of Pseudomonas aeruginosa for one patient in addition to the Pneumocystis carinii. Bronchoscopy with lavage was well tolerated, with few complications even among patients with significant tachypnea and hypoxia. Because of its relative safety and effectiveness, this procedure should be considered the first invasive measurement used for evaluation of parenchymal lung disease in this population of patients.
Conrad, Máire A; Dawany, Noor; Sullivan, Kathleen E; Devoto, Marcella; Kelsen, Judith R
Very early onset inflammatory bowel disease, diagnosed in children ≤5 years old, can be the initial presentation of some primary immunodeficiencies. In this study, we describe a 17-month-old boy with recurrent infections, growth failure, facial anomalies, and inflammatory bowel disease. Immune evaluation, whole-exome sequencing, karyotyping, and methylation array were performed to evaluate the child's constellation of symptoms and examination findings. Whole-exome sequencing revealed that the child was homozygous for a novel variant in ZBTB24, the gene associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome. This describes the first case of inflammatory bowel disease associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome in a child with a novel disease-causing mutation in ZBTB24 found on whole-exome sequencing.
Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.
Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.
Marina S. Sheremeta
Full Text Available Osteogenesis imperfecta (OI – is a group of genetically disorders, which are charaterized by a disturbed bone formation. In turn, the excess of thyroid hormones in Graves' disease (GD also posses a negative effect on bone tissue, thereby aggravating OI. That requires from the endocrinologist the most careful management of patients with the combination of these pathologies. In this article, we present a unique clinical case of a combination of GD and OI.
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Sillevis Smitt, J. Henk; Wulffraat, Nico M.; Kuijpers, Taco W.
Primary immunodeficiency disorders comprise serious and rare diseases, predominantly in children. The skin may be involved in a primary immunodeficiency and the cutaneous alterations such as infections, eczematous dermatitis, erythroderma, autoimmune dermatoses and vasculitis may be the basis for
Sellon, Debra C; Knowles, Donald P; Greiner, Ellis C; Long, Maureen T; Hines, Melissa T; Hochstatter, Tressa; Tibary, Ahmed; Dame, John B
Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.
Carriglio, Nicola; Klapwijk, Jan; Hernandez, Raisa Jofra; Vezzoli, Michela; Chanut, Franck; Lowe, Rhiannon; Draghici, Elena; Nord, Melanie; Albertini, Paola; Cristofori, Patrizia; Richards, Jane; Staton, Hazel; Appleby, Jonathan; Aiuti, Alessandro; Sauer, Aisha V
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Ex vivo gene therapy of patient bone-marrow CD34+ cells is an alternative treatment. In order to prepare for a marketing authorization application in the European Union, preclinical safety studies in mice were requested by the European Medicines Agency (EMA). A pilot study and a main biodistribution study were performed according to Good Laboratory Practice (GLP) at the San Raffaele Telethon Institute for Gene Therapy test facility. In the main study, human umbilical cord blood (UCB)-derived CD34+ cells were transduced with gamma-retroviral vector used in the production of GSK2696273. Groups of 10 male and 10 female NOD-SCID gamma (NSG) mice were injected intravenously with a single dose of transduced- or mock-transduced UCB CD34+ cells, and they were observed for 4 months. Engraftment and multilineage differentiation of blood cells was observed in the majority of animals in both groups. There was no significant difference in the level of chimerism between the two groups. In the gene therapy group, vector was detectable in lymphohemopoietic and nonlymphohemopoietic tissues, consistent with the presence of gene-modified human hematopoietic donor cells. Given the absence of relevant safety concerns in the data, the nonclinical studies and the clinical experience with GSK2696273 supported a successful application for market authorization in the European Union for the treatment of ADA-SCID patients, for whom no suitable human leukocyte
Full Text Available Abstract Background Children with Severe Combined Immunodeficiency (SCID lack autologous T lymphocytes and present with multiple infections early in infancy. Omenn syndrome is characterized by the sole emergence of oligoclonal auto-reactive T lymphocytes, resulting in erythroderma and enteropathy. Omenn syndrome (OS shares the genetic aetiology of T-B-NK+ SCID, with mutations in RAG1, RAG2, or DCLRE1C. Methods Patients diagnosed with T-B-NK+ SCID or phenotypes suggestive of Omenn syndrome were investigated by molecular genetic studies using gene tightly linked microsatellite markers followed by direct sequencing of the coding regions and splice sites of the respective candidate genes. Results We report the molecular genetic basis of T-B-NK+ SCID in 22 patients and of OS in seven patients all of Arab descent from Saudi Arabia. Among the SCID patients, six (from four families displayed four homozygous missense mutations in RAG1 including V433M, R624H, R394W, and R559S. Another four patients (from three familes showed 3 novel homozygous RAG2 mutations including K127X, S18X, and Q4X; all of which predict unique premature truncations of RAG2 protein. Among Omenn patients, four (from two families have S401P and R396H mutations in RAG1, and a fifth patient has a novel I444M mutation in RAG2. Seven other patients (six SCID and one OS showed a gross deletion in exons 1-3 in DCLRE1C. Altogether, mutations in RAG1/2 and DCLRE1C account for around 50% and 25%, respectively, in our study cohort, a proportion much higher than in previous reported series. Seven (24% patients lack a known genetic aetiology, strongly suggesting that they carry mutations in novel genes associated with SCID and Omenn disorders that are yet to be discovered in the Saudi population. Conclusion Mutation-free patients who lack a known genetic aetiology are likely to carry mutations in the regulatory elements in the SCID-causing genes or in novel genes that are yet to be discovered
Full Text Available The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. Whilst, the incidence of primary immunodeficiencies (PIDs is 1:10.000 births, that of secondary immunodeficiencies is more common and are associated with post transplantation immune dysfunction or with immunosuppressive medication for human immunodeficiency virus (HIV or with human T-cell lymphotropic virus (HTLV infection.After infection, malignancy is the most prevalent cause of death in both children and adults with primary immunodeficiency disorders (PIDs. PIDs more often associated with cancer include common variable immunodeficiency (CVID, Wiskott Aldrich syndrome (WAS, ataxia-telangiectasia (AT and severe combined immunodeficiency (SCID. This suggests that a protective immune response against both infectious non-self (pathogens and malignant self-challenges (cancer exist. The increased incidence of cancer has been attributed to defective elimination of altered or transformed cells and/or defective immunity towards cancer cells. The concept of abberant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies, the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.
Raptaki, Maria; Varela, Ioanna; Spanou, Kleopatra; Tzanoudaki, Marianna; Tantou, Sofia; Liatsis, Manolis; Constantinidou, Nikki; Bakoula, Chryssa; Roos, Dirk; Kanariou, Maria
Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency caused by the absence or dysfunction of one of NADPH oxidase subunits, with heterogeneous genetic aetiologies. The aim of this study was the CGD patient registry in Greece, the identification of the responsible genotype and
Roberts, Joseph L.; Lauritsen, Jens Peter H.; Cooney, Myriah; Parrott, Roberta E.; Sajaroff, Elisa O.; Win, Chan M.; Keller, Michael D.; Carpenter, Jeffery H.; Carabana, Juan; Krangel, Michael S.; Sarzotti, Marcella; Zhong, Xiao-Ping; Wiest, David L.; Buckley, Rebecca H.
CD3ζ is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T−B+NK+ severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3ζ gene. The few T cells present contained no detectable CD3ζ protein, expressed low levels of cell surface CD3ε, and were nonfunctional. CD4+CD8−CD...
Eyre, Toby A; Pelosi, Emanuela; McQuaid, Stephen; Richardson, Deborah; Newman, Joan; Hill, Kate; Veys, Paul; Davies, Graham; Orchard, Kim H
We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.
Hsu, Emory; Phadke, Varun K; Nguyen, Minh Ly T
We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease.
Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M
The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Full Text Available Both aflatoxin and the human immunodeficiency virus (HIV cause immune suppression and millions of HIV-infected people in developing countries are chronically exposed to aflatoxin in their diets. We investigated the possible interaction of aflatoxin and HIV on immune suppression by comparing immune parameters in 116 HIV positive and 80 aged-matched HIV negative Ghanaians with high (≥0.91 pmol/mg albumin and low (<0.91 pmol/mg albumin aflatoxin B1 albumin adduct (AF-ALB levels. AF-ALB levels and HIV viral load were measured in plasma and the percentages of leukocyte immunophenotypes and cytokine expression were determined using flow cytometry. The cross-sectional comparisons found that (1 among both HIV positive and negative participants, high AF-ALB was associated with lower perforin expression on CD8+ T-cells (P=.012; (2 HIV positive participants with high AF-ALB had significantly lower percentages of CD4+ T regulatory cells (Tregs; P=.009 and naive CD4+ T cells (P=.029 compared to HIV positive participants with low AF-ALB; and (3 HIV positive participants with high AF-ALB had a significantly reduced percentage of B-cells (P=.03 compared to those with low AF-ALB. High AF-ALB appeared to accentuate some HIV associated changes in T-cell phenotypes and in B-cells in HIV positive participants.
Affandi, Jacquita S; Aghafar, Zayd K A; Rodriguez, Benigno; Lederman, Michael M; Burrows, Sally; Senitzer, David; Price, Patricia
Most human immunodeficiency virus (HIV) patients are seropositive for cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This observation may reflect variations in genes affecting inflammatory and natural killer cell responses. DNA samples were collected from 240 HIV-infected patients followed at the University Hospitals/Case Medical Center (Cleveland, OH) between 1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37) experienced CMV disease. Genotypes were determined using allele-specific fluorescent probes or multiplex polymerase chain reaction sequence-specific primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease in African American patients (p = 0.04 and p = 0.02, respectively). IL10-1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were associated with low nadir CD4(+) T cell counts in African American patients (p = 0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA-1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In general, polymorphisms associated with CMV disease and CD4(+) T cell counts were distinct in Caucasian and African American patients in the United States. The LILRB1 I142T polymorphism was associated with both CMV disease and low nadir CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir CD4(+) T cell count in African American patients was DARC T-46C. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. All rights reserved.
[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].
Gerych, P; Yatsyshyn, R
Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.
Full Text Available BACKGROUND: Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. METHODOLOGY/PRINCIPAL FINDINGS: We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID. Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. CONCLUSIONS AND SIGNIFICANCE: The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.
Prevalência da imunodeficiência severa combinada em cavalos da raça Árabe em plantéis de Minas Gerais e São Paulo Prevalence of the severe combined immunodeficiency disease in Arabian horses raised in Minas Gerais and São Paulo-Brazil
Full Text Available Neste estudo foram genotipados 205 cavalos da raça Árabe, criados nos estados de Minas Gerais e São Paulo, via DNA por meio de PCR, para determinação da presença do gene mutante SCID. Os resultados mostraram 98,5% de animais normais (202/205 e 1,5% de portadores (3/205. Pela análise da genealogia dos portadores identificados pode-se, ainda, confirmar a participação de um garanhão anteriormente identificado como provável disseminador da doença.In the present study, 205 Arabian horses raised in Minas Gerais and São Paulo states, Brazil, were genotyped using the PCR technique. The results showed 98.5% of normals (202/205 and 1.5% of SCID carriers (3/205. Checking the pedigrees of the three carriers was possible to confirm the participation of one stallion first identified as the possible disease disseminator.
Wasserheit, J N
The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135
E N Anyabolu
Full Text Available Human immunodeficiency virus (HIV infection is a common cause of chronic kidney disease (CKD in Sub-Saharan Africa. This study aims at identifying the prevalence and predictors of CKD in newly diagnosed HIV patients in Owerri, South East Nigeria. This was a cross-sectional study consisting of 393 newly diagnosed HIV-seropositive subjects and 136 age- and sex-matched seronegative subjects as controls. CKD was defined as 24-hour urine protein (24-HUP ≥0.3 g and/or glomerular filtration rate (GFR < 60 ml/min. Subjects were recruited from the HIV clinic and the Medical Outpatient Department of Federal Medical Centre, Owerri. Clinical and anthropometric data were collected. Relevant investigations were performed, including HIV screening and relevant urine and blood investigations. The mean age of the HIV subjects was 38.84 ± 10.65 years. CKD was present in 86 (22.9% HIV subjects and 11 (8.l % controls. Low waist circumference (WC, high serum creatinine, high spot urine protein/creatinine ratio (SUPCR, high 24-HUP/creatinine Ratio (24-HUPCR, high 24-HUP/osmolality Ratio (24-HUPOR predicted CKD in HIV subjects. CKD prevalence is high (22.9% among newly diagnosed HIV patients in South East Nigeria. The predictors of CKD included WC, serum creatinine, SUPCR, 24-HUPCR, and 24-HUPOR.
Elisa Vicenzi, Pietro Liò, Guido Poli
The human immunodeficiency virus type-1 (HIV-1) is the etiological agent of the acquired immunodeficiency syndrome (AIDS), a disease highly lethal in the absence of combination antiretroviral therapy. HIV infects CD4+ cells of the immune system (T cells, monocyte-macrophages and dendritic cells) via interaction with a universal primary receptor, the CD4 molecule, followed by a mandatory interaction with a second receptor (co-receptor) belonging to the chemokine receptor family. Apart from som...
Full Text Available Severe combined immunodeficiency (SCID is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID. Bronchial alveolar lavage fluid from both patients grew Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta gene is believed to be important in T cell differentiation and maturation. The present article reminds pediatricians and pediatric respirologists that the key to diagnosing SCID is to have a high index of suspicion if there is poor response to conventional therapies.
Kuijpers, Taco W; van Leeuwen, Ester M M; Barendregt, Barbara H; Klarenbeek, Paul; aan de Kerk, Daan J; Baars, Paul A; Jansen, Machiel H; de Vries, Niek; van Lier, René A W; van der Burg, Mirjam
Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.
S Rochelle Mikkelsen
Full Text Available Feline immunodeficiency virus (FIV infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+CD25(hiFoxP3(+ immunosuppressive regulatory T (Treg cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+ T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.
Mikkelsen, S Rochelle; Long, Julie M; Zhang, Lin; Galemore, Erin R; VandeWoude, Sue; Dean, Gregg A
Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+)CD25(hi)FoxP3(+) immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+) T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.
Full Text Available Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky SCID, carrying hypomorphic mutations in Rag1 and Lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs. While the ability of mTECs to express Aire is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens (TSAs is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in Rag1 and Lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation.
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.
Full Text Available Primary immunodeficiencies (PID are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.
Kanapathipillai, Rupa; Hickey, Martha; Giles, Michelle
This article aims to review currently available evidence for women infected with human immunodeficiency virus (HIV) and menopause and to propose clinical management algorithms. Key studies addressing HIV and menopause have been reviewed, specifically age of menopause onset in HIV-infected women, frequency of menopausal symptoms, comorbidities associated with HIV and aging (including cardiovascular disease and bone disease), treatment of menopausal symptoms, and prevention of comorbidities in HIV-infected women. Studies suggest an earlier onset of menopause in HIV-infected women, with increased frequency of symptoms. Cardiovascular disease risk may be increased in this population, with combination antiretroviral therapy (cART) and chronic inflammation associated with HIV, contributing to increased risk. Chronic inflammation and cART have been independently implicated in bone disease. No published data have assessed the safety and efficacy of hormone therapy in relation to symptoms of menopause, cardiovascular risk, and bone disease among HIV-infected women. Few studies on menopause have been conducted in HIV-infected women compared with HIV-uninfected women. Many questions regarding age of menopause onset, frequency of menopausal symptoms and associated complications such as bone disease and cardiovascular disease, and efficacy of treatment among HIV-infected women remain. The incidence and severity of some of these factors may be increased in the setting of HIV and cART.
Reimann, J; Rudolphi, A; Spiess, S
We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...
Cameron D William
Full Text Available Abstract Background Bacille Calmette-Guérin (BCG vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID incidence, above which BCG is associated with greater risk than benefit. Methods A Markov model was developed to simulate the natural histories of tuberculosis (TB and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs. Results In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000. Conclusion The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control – including early detection and treatment of infection – may be a safer, more effective alternative.
Bęczkowski, Paweł M; Techakriengkrai, Navapon; Logan, Nicola; McMonagle, Elizabeth; Litster, Annette; Willett, Brian J; Hosie, Margaret J
Feline immunodeficiency virus (FIV) infection is mediated by sequential interactions with CD134 and CXCR4. Field strains of virus vary in their dependence on cysteine-rich domain 2 (CRD2) of CD134 for infection. Here, we analyse the receptor usage of viral variants in the blood of 39 naturally infected cats, revealing that CRD2-dependent viral variants dominate in early infection, evolving towards CRD2-independence with disease progression. These findings are consistent with a shift in CRD2 of CD134 usage with disease progression.
This article reports on the prevalence of AIDS and sexually transmitted diseases (STDs) in Southeast Asia. The spread of HIV infection in this region has been predicted to be worse than that of Africa. The high-prevalence countries are Thailand, Cambodia, and Myanmar, where prevalence rates in the population at risk (15-49 year olds) are up to 2%; while low prevalence countries with rates of 0.1% include the Philippines, Indonesia, Laos, Brunei, and Singapore. Heterosexual transmission in Southeast Asia is the main mode of spread of HIV. Another route is through migration, rural-to-urban or international migration of people seeking jobs; with concurrent loneliness and anonymity, they become vulnerable to STDs and HIV infection. Intravenous drug use poses an increasing risk of transmission. The unavailability of data in some countries makes it difficult to evaluate the extent of the epidemic or if there's an impending epidemic. There are a number of caveats to the data compilation from various countries. These include the following: under-reporting of cases; underdiagnosis; missed diagnosis; and differences in the time of data collection. It is clear that poverty, illiteracy, and poor access to educational information in most countries in this region facilitate the rapid spread of HIV. These coupled with lack of primary health care services, and in most instances, enormously high cost of drugs make the pain and suffering due to the HIV/AIDS epidemic a human disaster far worse than the ravages of war.
Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy
British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.
Hurst, John R; Verma, Nisha; Lowe, David; Baxendale, Helen E; Jolles, Stephen; Kelleher, Peter; Longhurst, Hilary J; Patel, Smita Y; Renzoni, Elisabetta A; Sander, Clare R; Avery, Gerard R; Babar, Judith L; Buckland, Matthew S; Burns, Siobhan; Egner, William; Gompels, Mark M; Gordins, Pavels; Haddock, Jamanda A; Hart, Simon P; Hayman, Grant R; Herriot, Richard; Hoyles, Rachel K; Huissoon, Aarnoud P; Jacob, Joseph; Nicholson, Andrew G; Rassl, Doris M; Sargur, Ravishankar B; Savic, Sinisa; Seneviratne, Suranjith L; Sheaff, Michael; Vaitla, Prashantha M; Walters, Gareth I; Whitehouse, Joanna L; Wright, Penny A; Condliffe, Alison M
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Veenstra, J.; Veugelers, P. J.; Keet, I. P.; van der Ven, A. J. A. M.; Miedema, F.; Lange, J. M.; Coutinho, R. A.
We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid
Full Text Available There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID. Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T, whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD, 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.
Borte, Stephan; Janzi, Magdalena; Pan-Hammarström, Qiang; von Döbeln, Ulrika; Nordvall, Lennart; Winiarski, Jacek; Fasth, Anders; Hammarström, Lennart
There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD), 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.
She hopes to use the knowledge gained to improve immunology diagnostic services in South Africa. Melinda Suchard ... detection of regulatory T cells and indoleamine 2,3 dioxygenase. Dr Suchard runs a diagnostic flow cytometry laboratory for kidney transplant immunology. .... born to a mother who has previously lost.
detection of regulatory T cells and indoleamine 2,3 dioxygenase. Dr Suchard runs a diagnostic flow cytometry laboratory for kidney transplant immunology. She co-ordinates a Short ... which help B cells to produce antibody. CD4+ .... SCID: Haematopoietic stem cell transplant ... lymphoma in some recipients. • Phagocytic ...
Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of
Pedersen, Anders Elm; Gad, M; Kristensen, N N
Immunomodulatory dendritic cells (DCs) that induce antigen-specific T-cell tolerance upon in vivo adoptive transfer are promising candidates for immunotherapy of autoimmune diseases. The feasibility of such a strategy has recently proved its efficacy in animal models of allotransplantation and ex...
Kimura, H.; Terado, T.; Ikebuchi, M.; Aoyama, T.; Komatsu, K.; Nozawa, A.
The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of DNA damage were examined in fibroblasts of the severe combined immunodeficient (scid) mouse. These cells are hypersensitive to ionizing radiation because of a deficiency in the repair of double-strand breaks. Hypertonic treatment caused radiosensitization due to a fixation of potentially lethal damage (PLD) in scid cells, demonstrating that scid cells normally repair PLD. To assess the kinetics of the repair of PLD, hypertonic treatment was delayed for various times after irradiation. Potentially lethal damage was repaired during these times in isotonic medium at 37 degrees C. It was found that the rate of repair of PLD was much slower in scid cells than in BALB/c 3T3 cells, which have a open-quotes wild-typeclose quotes level of radiosensitivity. This fact indicates that the scid mutation affects the type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid cells containing fragments of human chromosome 8, which complements the radiosensitivity of the scid cells, the rate of repair was restored to a normal level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD which is sensitive to hypertonic treatment. 29 refs., 3 figs
Byk, Tamara; Kahn, Joy; Kollet, Orit; Petit, Isabelle; Samira, Sarit; Shivtiel, Shoham; Ben-Hur, Herzl; Peled, Amnon; Piacibello, Wanda; Lapidot, Tsvee
The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.
Anderson Dik Wai Luk
Full Text Available BackgroundSevere combined immunodeficiency (SCID is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH has been associated with earlier diagnosis.ObjectiveThe aim of this study was to identify the clinical features that affect age at diagnosis (AD and time to the diagnosis of SCID.MethodsFrom 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP, and AD were selected for study.ResultsA total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57. A total of 29 patients had a positive FH. Candidiasis (n = 27 and bacillus Calmette–Guérin (BCG vaccine infection (n = 19 were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002 and diagnosis by 2 months (p = 0.008, but not shorter time to diagnosis (p = 0.494. Candidiasis was associated with later AD by 2 months (p = 0.008 and longer time to diagnosis by 0.55 months (p = 0.003. BCG infections were not associated with age or time to diagnosis.ConclusionFH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of
Full Text Available In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases.
Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.
Patick, A K; Boritzki, T J; Bloom, L A
Nelfinavir mesylate (formerly AG1343) is a potent and selective, nonpeptidic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that was discovered by protein structure-based design methodologies. We evaluated the antiviral and cytotoxic effects of two-drug combinations of nelfinavir with the clinically approved antiretroviral therapeutics zidovudine (ZDV), lamivudine (3TC), dideoxycytidine (ddC; zalcitabine), stavudine (d4T), didanosine (ddI), indinavir, saquinavir, and ritona...
Chaudhury, Chloe S; Purdy, Julia B; Liu, Chia-Ying; Morse, Caryn G; Stanley, Takara L; Kleiner, David; Hadigan, Colleen
Non-alcoholic fatty liver disease is common in human immunodeficiency virus, but there are no approved therapies. The aim of this open-label proof-of-concept study was to determine the effect of the mineralocorticoid receptor antagonist eplerenone on hepatic fat in human immunodeficiency virus-infected patients with hepatic fat ≥5% by magnetic resonance spectroscopy. Five subjects received eplerenone (25 mg daily × 1 week followed by 50 mg daily × 23 weeks). Laboratory tests were done at each visit, and the primary endpoint, change in hepatic fat content, was determined by MRI spectroscopy at baseline and week 24. The study was stopped early after observing unexpected significant increases in hepatic fat at week 24 (mean increase 13.0 ± 7.3%, P = .02). The increases in steatosis were accompanied by a tendency for transaminase values to decrease (alanine aminotransferase mean change -14 ± 16 IU/L, P = .14). There were no consistent changes in other metabolic parameters or blood pressure. Repeat assessment of hepatic steatosis 1-2 months after stopping study medication revealed improvements in steatosis towards baseline values. The unexpected observation of increased hepatic steatosis with the administration of eplerenone led to early termination of the investigation. While limited because of the small number of participants and the open-label design, this study provides data to suggest that mineralocorticoid receptor antagonism with eplerenone may not be an effective approach to treat hepatic steatosis in human immunodeficiency virus or the general population. Additional research is needed to determine the pathophysiological mechanism behind these unanticipated observations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia
Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.
Michos, Athanasios; Tzanoudaki, Marianna; Villa, Anna; Giliani, Silvia; Chrousos, George; Kanariou, Maria
Severe combined immunodeficiencies (SCID) are a heterogeneous group of genetic disorders characterized by a blockade or impairment of both cellular and humoral immunity. Several epidemiological studies in different geographic areas have shown that the most common type of SCID affecting almost half of these patients is the X-linked common γ-chain (γ(c)) deficiency. The objective of the study was to document the incidence and types of SCID in our area. We conducted a retrospective analysis of patients who were diagnosed with SCID in the major immunology center in Greece for a 20-year period. During the study period, 30 children from 27 unrelated families with final diagnosis of SCID were identified. The incidence of SCID in Greece is estimated at 1.7 cases per 100,000 live births. Out of 30 children, 19 were boys (63.3%) and 26 (86.7%) had Greek maternal origin. Lymphocyte immunophenotypes that were identified were T(-)B(-)NK(+) in 12 (40%) children, T(-)B(+)NK(-) in six (20%), T(-)B(+)NK(+) in three (10%), T(-)B(-)NK(-) in two (6.7%) and T(+)B(+/-)NK(+) in seven (23.4%) (among them, four [13.4%] females with Omenn's syndrome). Molecular diagnosis was available for 12 children: γ(c) (2) with non Greek maternal origin, Jak3 (2), Rag1 (2), Artemis (3), ADA deficiency (2), PNP deficiency (1). Out of the 26 children of Greek maternal origin diagnosed with SCID representing 23 distinct families, only two (8.7%) had lymphocyte immunophenotype compatible with γ(c)-chain gene mutation (no molecular testing or enough DNA was available for them at the time of diagnosis). Findings of the present study suggest that, for unknown reasons, mutations of the γ(c) chain of several cytokine receptors have a rare occurrence in our area.
Tsujimura, Akira; Fukuhara, Shinichiro; Soda, Tetsuji; Takezawa, Kentaro; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Adachi, Shigeki; Tokita, Yoriko; Nomura, Taisei
To evaluate histologic change in human prostate samples treated with dutasteride and to elucidate direct effects of dutasteride on human prostate tissue, the present study was conducted by using a xenograft model with improved severe combined immunodeficient (super-SCID) mice, although it is well known that dutasteride reduces prostate volume. After establishment of a xenograft model of human benign prostatic hyperplasia in morphology and function, samples implanted into super-SCID mice with and without dutasteride were evaluated pathohistologically at 2 and 6 months after initiation of dutasteride administration. The proliferative index evaluated by Ki-67 staining was significantly lower in the dutasteride group than the control at 2 and 6 months after administration. Apoptotic index evaluated by the terminal transferase TdT-mediated dUTP-biotin nick end labeling staining was higher in the dutasteride group than the control at 2 and 6 months after administration. Quick scores in the dutasteride group for staining of both cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) were significantly lower than those in the control group at 2 and 6 months after administration. Dutasteride inhibits cell proliferation and induces apoptosis of prostatic cells, causing a reduced prostate volume. Furthermore, decreased expression of Cox-2 and RhoA within benign prostatic hyperplasia tissue by dutasteride may induce an early effect on improvement of lower urinary tract symptoms, probably by attenuating inflammation reaction of the prostate and decreasing intraurethral pressure, other than the mechanism of reduced prostate volume. Copyright © 2015 Elsevier Inc. All rights reserved.
Maria Elena Maccari
Full Text Available Activated phosphoinositide 3-kinase (PI3K δ Syndrome (APDS, caused by autosomal dominant mutations in PIK3CD (APDS1 or PIK3R1 (APDS2, is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2. Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission, while bowel inflammation (3 complete, 3 partial, 9 no remission and cytopenia (3 complete, 2 partial, 9 no remission responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.
... advise you about these. Until a child's immune system develops adequate protection after a bone marrow transplant, you can help ... infections than usual, discuss the possibility of immune deficiency with your doctor. If your child has a ... by: Stephen J. McGeady, MD Date reviewed: ...
Reekie, Joanne; Kosa, Csaba; Engsig, Frederik
In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported...
High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid
Booiman, Thijs; Wit, Ferdinand W.; Maurer, Irma; de Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Booiman, T.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé, H. G.; Franceschi, C.; Garagnani, P.
Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation,
High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid
Booiman, Thijs; Wit, Ferdinand W N M; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A; Harskamp, Agnes M; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A; Kalsbeek, A.
BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte
Full Text Available Human immunodeficiency virus (HIV infection confers an increased risk of cardiovascular disease, including acute coronary syndrome (ACS. Patients with perinatally acquired HIV may be at increased risk due to the viral infection itself and exposure to HAART in utero or as part of treatment. A 20-year-old female with transplacentally acquired HIV infection presented with symptoms of transient aphasia, headache, palpitations, and blurry vision. She was admitted for hypertensive emergency with blood pressure 203/100 mmHg. Within a few hours, she complained of typical chest pain, and ECG showed marked ST depression. Troponin I levels escalated from 0.115 to 10.8. She underwent coronary angiogram showing 95% stenosis of the right coronary artery (RCA and severe peripheral arterial disease including total occlusion of both common iliacs and 95% infrarenal aortic stenosis with collateral circulation. She underwent successful percutaneous intervention with a drug-eluting stent to the mid-RCA. Patients with HIV are at increased risk for cardiovascular disease. Of these, coronary artery disease is one of the most critical complications of HIV. Perinatally acquired HIV infection can be a high-risk factor for cardiovascular disease. A high degree of suspicion is warranted in such patients, especially if they are noncompliant to their ART.
Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian
This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...
Full Text Available Purpose. To report a case of bilateral Coats’ disease combined with retinopathy of prematurity (ROP. Case. Retinal vascularization was complete in the right eye, whereas zone III, stage 3 ROP and preplus disease were observed in the left eye at 43 weeks of postmenstrual age (PMA in a 31-week premature, 1200-g neonate. Intraretinal exudates developed and retinal hemorrhages increased in the left eye at 51 weeks of PMA. Diode laser photocoagulation (LP was applied to the left eye. Exudates involved the macula, and telangiectatic changes developed one month following LP. Additional LP was applied to the left eye combined with intravitreal bevacizumab (IVB injection at 55 weeks of PMA. Disease regressed one month after the additional therapy. At the 14-month examination of the baby, telangiectatic changes and intraretinal exudates were observed in the right eye. Diode LP was applied to the right eye combined with IVB injection. Exudates did not resolve completely, and cryotherapy was applied one month following LP. Retinal findings regressed three months following the cryotherapy. Conclusion. This is the first report of presumed bilateral Coats’ disease combined with ROP. If Coats’ disease could be diagnosed at early stages, it would be a disease associated with better prognosis.
Marchiori, Edson; Melo, Alessandro Severo Alves de; Ossa, Alfonso Jaramillo
In this article are reviewed the principal radiologic manifestations of inflammatory and tumoral diseases the compromise the lungs of patients with acquired immunodeficiency syndrome. In the group of inflammatory diseases the radiologic aspects of pneumocystosis, cytomegalovirus disease, cryptococcosis, tuberculosis and bacterial pneumonias are emphasized. In the neoplasic diseases' group the aspects of lymphoma and Kaposi's sarcoma are specially presented. (author)
Szczawinska-Poplonyk, Aleksandra; Wojsyk-Banaszak, Irena; Jonczyk-Potoczna, Katarzyna; Breborowicz, Anna
Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection. We report on the case of a 7-year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease. The diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions.
Full Text Available Authors report an 11-month-old female child, who presented with recurrent episodes of colicky abdominal pain and diarrhea. An abdominal ultrasound revealed small bowel intussusception. She was also noted to have a thick walled gall bladder and a solitary gallstone. Further investigations confirmed the diagnosis of coeliac disease. The combination of small bowel intussusception, coeliac disease and cholelithiasis is unique and has not been reported in the literature.
Full Text Available Abstract Objective Orthotopic-liver-transplantation (OLT in patients with Human-Immunodeficiency-Virus infection (HIV and end-stage-liver-disease (ESDL is rarely reported. The purpose of this study is to describe our institutional experience on OLT for HIV positive patients. Material and methods This is a retrospective study of all HIV-infected patients who underwent OLT at the University Hospital of Essen, from January 1996 to December 2009. Age, sex, HIV transmission-way, CDC-stage, etiology of ESDL, concomitant liver disease, last CD4cell count and HIV-viral load prior to OLT were collected and analysed. Standard calcineurin-inhibitors-based immunosuppression was applied. All patients received anti-fungal and anti-pneumocystis carinii pneumonia prophylaxis post-OLT. Results Eight transplanted HIV-infected patients with a median age of 46 years (range 35-61 years were included. OLT indications were HCV (n = 5, HBV (n = 2, HCV/HBV/HDV-related cirrhosis (n = 1 and acute liver-failure (n = 1. At OLT, CD4 cell-counts ranged from 113-621 cells/μl, and HIV viral-loads from Conclusions OLT in HIV-infected patients and ESLD is an acceptable therapeutic option in selected patients. Long-term survival can be achieved without HIV disease-progression under antiretroviral therapy and management of the viral hepatitis co-infection.
Gupta, Mrinal; Mahajan, Vikram K; Chauahn, Pushpinder S; Mehta, Karainder S; Rawat, Ritu; Shiny, T N
Although modification of behavioral practices among human immunodeficiency virus (HIV)-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS). To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13) years. The majority, 112 (74.67%) patients were between 20 and 50 years of age and 116 (77.3%) patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2%) patients among affected males. Only 129 (86%) respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3%) respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7%) respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90%) patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.
Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten
Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.
Alex Panizza Jalkh
Conclusion: The high prevalence of C. trachomatis infection among human immunodeficiency virus-infected men highlights that screening human immunodeficiency virus-infected men for C. trachomatis, especially among men having sex with men, is paramount to control the spread of C. trachomatis infection.
Saito, Shinta; Kurosawa, Aya; Adachi, Noritaka
In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V(D)J recombination.
Yusuf, Salim; Attaran, Amir; Bosch, Jackie; Joseph, Philip; Lonn, Eva; McCready, Tara; Mente, Andrew; Nieuwlaat, Robby; Pais, Prem; Rodgers, Anthony; Schwalm, J-D; Smith, Richard; Teo, Koon; Xavier, Denis
Combination pills containing aspirin, multiple blood pressure (BP) lowering drugs, and a statin have demonstrated safety, substantial risk factor reductions, and improved medication adherence in the prevention of cardiovascular disease (CVD). The individual medications in combination pills are already recommended for use together in secondary CVD prevention. Therefore, current information on their pharmacokinetics, impact on the risk factors, and tolerability should be sufficient to persuade regulators and clinicians to use fixed-dose combination pills in high-risk individuals, such as in secondary prevention. Long-term use of these medicines, in a polypill or otherwise, is expected to reduce CVD risk by at least 50-60% in such groups. This risk reduction needs confirmation in prospective randomized trials for populations for whom concomitant use of the medications is not currently recommended (e.g. primary prevention). Given their additive benefits, the combined estimated relative risk reduction (RRR) in CVD from both lifestyle modification and a combination pill is expected to be 70-80%. The first of several barriers to the widespread use of combination therapy in CVD prevention is physician reluctance to use combination pills. This reluctance may originate from the belief that lifestyle modification should take precedence, and that medications should be introduced one drug at a time, instead of regarding combination pills and lifestyle modification as complementary and additive. Second, widespread availability of combination pills is also impeded by the reluctance of large pharmaceutical companies to invest in development of novel co-formulations of generic (or 'mature') drugs. A business model based on 'mass approaches' to drug production, packaging, marketing, and distribution could make the combination pill available at an affordable price, while at the same time providing a viable profit for the manufacturers. A third barrier is regulatory approval for novel
Full Text Available Levels of Kappa-deleting recombination excision circles (KRECs, T-cell receptor excision circles (TRECs, and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.
Zhang, Zhi-yong; Zhao, Xiao-dong; Wang, Mo; Yu, Jie; An, Yun-fei; Yang, Xi-qiang
Mutation in the interleukin-7 receptor-alpha (IL-7R alpha) chain causes a rare type of severe combined immunodeficiency (SCID) with presence of NK cells in the peripheral blood. Here we report the molecular and clinical characterization of a compound heterozygosity mutation in the interleukin-7 receptor-alpha gene that resulted in SCID in a patient firstly from China. A 5 month-old male patient and his parents were enrolled in this study. Since 15 days of age, the patient had had recurrent fever, persistent cough and diarrhea. He was in poor general condition with pyorrhea and ulceration of the BCG scar. His brother died of severe infection at 4 months of age. He was initially diagnosed as SCID according to clinical manifestation and immunological analysis. A panel of SCID candidate genes including IL-2RG, RAG1/RAG2 and IL-7R alpha of patient and his parents were amplified by polymerase chain reaction (PCR) from genomic DNA. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the IL-7R alpha transcripts. Sequencing was performed directly on the PCR products forward and reversely. The serum immunoglobulin (Ig) profile was IgG 6867 mg/L (normal range, 3050 - 8870 mg/L); IgM 206 mg/L and IgA 249 mg/L, IgE 2.3 IU/ml (normal range microscope and by culture. The patient had a compound heterozygosity mutation in the IL-7R alpha gene:on one allele, there was a splice-junction mutation in intron 4 (intron 4(+1)G > A), for which his father was a carrier; whereas on the other allele, a nonsense mutation at position 638 in exon 5 with a premature stop codon (638 C > T, R206X) was identified, for which his mother was a carrier. The splice-junction mutation in intron 4 of IL-7R alpha was firstly reported. The IL-7R alpha mRNA expression of the patient was remarkably reduced whereas the parents had relatively normal IL-7R alpha mRNA expression. IL-7R alpha cDNA of the patient was amplified by nested PCR. The PCR products were purified, cloned with a TA
Noh, L M; Nasuruddin, B A; Abdul Latiff, A H; Noah, R M; Kamarul Azahar, M R; Norzila, M Z; Zulkifli, I; Gill, H K; Nik Zainal, N I; Suhaimi, A W M; Nik Khairulddin, N Y; Maraina, H; Intan, H I; Mat, I; Shahnaz, M; B H O, Azizi
To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007. Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.
Mauri Pont, Marta; Borrallo Almansa, Rosa Maria; Almada Rivas, Guido; Carbó Díez, Miriam; Solé Arnau, Rosa; García Restoy, Enric
Cardiovascular disease among human immunodeficiency virus (HIV) infected patients is more frequent than in the general population. Peripheral arterial disease measured by ankle-brachial index (ABI) and cardiovascular risk factors (CVRF) is not well known in all groups of HIV-infected patients. Transversal study of HIV-infected patients >45 years, seen as outpatients in hospital (HO) in 2008 and patients institutionalized in a prison in 2009. Cardiovascular risk factors, information on the HIV infection and healthy lifestyles were evaluated. ABI was measured at rest and was considered pathological when a value ≤ 0.9 or ≥ 1.3 was obtained. We included 71 patients (mean age of 50.6 ± 6.9 years, 86% male), 32 HO and 39 in prison. The most prevalent CVRF was smoking (80.2%) followed by an altered lipid profile (63.3%). The evolution time of HIV infection was 13.1 ± 7.1 years. 74.6% of patients didn't follow a heart-healthy diet and 25% were sedentary. The ABI was low in 7 cases (9.8%) and ≥ 1.3 in one. Patients in prison were younger, the rate of smokers and of individuals with low HDL were higher, the time of evolution of the HIV infections was longer and they were less adherent to a heart-healthy diet than in HO, reaching in all cases statistical significance (Pde Arteriosclerosis. Published by Elsevier España. All rights reserved.
Barkanov, A.I.; Morozov, A.I.; Pirogov, A.I.; Postnikov, D.A.; Shadyeva, M.M.; Roshchina, V.S.; Devyatykh, Yu.N.
The authors made observations of 123 patients with the Itsenko - Cushing disease. The mild form of the disease was diagnosed in 27.7 per cent of the patients; moderate in 52 percent, and severe in 20.3 per cent of the patients. A total of 78 patients underwent tele-gamma-therapy in doses of 40-45 Gy, and 45 patients underwent combined treatment consisting in unilateral adrenalectomy and irradiation with the same doses. Protracted remissions with a reverse development of the symptoms of the disease were reached in 69.2 per cent of the patients who had undergone radiation treatment and in 64.4 per cent of the patients who had undergone combined treatment. Radiotherapy was most effective in patients with mild and moderate forms of Itsenko-Cushing's disease, in case of a severe form combined treatment is indicated. Optimal single focal doses are 1.6-1.8 Gy, and cumulative ones 40-45 Gy
Weber, Rainer; Sabin, Caroline A.; Friis-Møller, Nina; Reiss, Peter; El-Sadr, Wafaa M.; Kirk, Ole; Dabis, Francois; Law, Matthew G.; Pradier, Christian; de Wit, Stephane; Akerlund, Börje; Calvo, Gonzalo; D'Arminio Monforte, Antonella; Rickenbach, Martin; Ledergerber, Bruno; Phillips, Andrew N.; Lundgren, Jens D.
BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related
Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne
Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.
Fayand, A; Sarrabay, G; Belot, A; Hentgen, V; Kone-Paut, I; Grateau, G; Melki, I; Georgin-Lavialle, S
Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Neumann, Mary Spink; O'Donnell, Lydia; Doval, Alexi San; Schillinger, Julia; Blank, Susan; Ortiz-Rios, Elizabeth; Garcia, Trinidad; O'Donnell, Carl R
Prevention providers wonder whether benefits achieved in the original, researcher-led, efficacy trials of interventions are replicated when the intervention is delivered in real-world settings by their agency's staff. A replication study was conducted at 2 public sexually transmitted disease (STD) clinics (New York City and San Juan, PR). Using a controlled trial design, intervention (VOICES/VOCES) and comparison conditions (regular clinic services) were assigned in alternating 4-week blocks. Trained agency staff delivered the intervention. Effectiveness was assessed for incident STDs, redemption of coupons for condoms at neighborhood location after the visit, and improved knowledge and attitudes about STDs and condoms. A total of 3365 patients were recruited, completed the protocol, and followed through STD surveillance systems for an average of 17 months. Of 397 with an incident infection, 226 (13.4%) were among those enrolled during comparison blocks; 171 were among those in the intervention condition (10.2%). Controlling for site and gender, participants enrolled during intervention blocks were significantly less likely to have an incident STD reported to the surveillance system (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96). Intervention block participants scored higher on scales of STD knowledge (4.89 vs. 3.87, P VOCES redeemed condoms (P < 0.05). Positive effects were more consistent in New York, which may be related to fidelity of implementation. A packaged human immunodeficiency virus prevention intervention can be delivered by agencies, with benefits similar to those achieved in the research setting.
Zheng, Xi; Cui, Xiao-Xing; Gao, Zhi; Verano, Michael; Huang, Mou-Tuan; Liu, Yue; Rabson, Arnold B; Conney, Allan H
In the present study, the effects of 12-O-tetra-decanoylphorbol-13-acetate (TPA) alone or in combination with gemcitabine on the growth of Panc-1 pancreatic cancer cells cultured in vitro or grown in NCr immunodeficient nude mice were investigated. Combinations of TPA and gemcitabine synergi-stically inhibited the growth and induced apoptosis in Panc-1 cells. The combination of TPA (0.16 nM) and gemcitabine (0.5 µM) induced a marked increase in phosphorylated c-Jun NH2-terminal kinase (JNK) in the Panc-1 cells. In animal experiments, NCr nude mice with established Panc-1 tumors received daily intraperitoneal (i.p.) injections of TPA (50 ng/g body weight/day) or gemcitabine (0.5 µg/g body weight/day) alone or in combination for 26 days. Treatment with daily i.p. injections of low doses of TPA or gemcitabine alone had a modest inhibitory effect on the growth of the tumors. However, the combination of low doses of TPA and gemcitabine more potently inhibited the growth of Panc-1 tumors than either agent used individually. Treatment with TPA or gemcitabine alone or in combination did not affect the body weight of the animals. Clinical trials with TPA alone or in combination with gemcitabine on patients with pancreatic cancer are warranted in order to confirm our results.
Castaner, Eva; Gallardo, Xavier; Maria Mata, Josep; Esteba, Lola
Nearly all patients infected with HIV experience respiratory infection at some point in the course of their illness. The spectrum of infections is varied and in order to generate a useful differential diagnosis based on imaging findings it is imperative for the radiologist to be aware of changing trends in disease prevalence and epidemiology, and the possible pathology related to new therapies. The characterization of the radiographic pattern in correlation with clinical findings and laboratory values (in particular the degree of immunosuppression as reflected in the CD4 level) would be helpful in narrowing the differential diagnosis of infectious pulmonary disease in HIV-positive patients. The most common radiologic patterns considered include areas of ground-glass, consolidation, nodules, and lymphadenopathy. We also include airways diseases and cavitary/cystic lesions because their prevalence has increased over recent years, and we also mention the significance of a normal chest radiograph in the suspicion of a lung infection. In most cases, the clinical and radiographic findings are sufficient for confident diagnosis. The radiologic diagnosis of thoracic infections in patients with AIDS has improved with the use of CT. The greatest value of CT is in excluding lung disease when the radiographic findings are equivocal and in confirming the presence of clinically suspected disease when the radiograph is normal
Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima
Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.
Johnson, Britney L; Tesoriero, James; Feng, Wenhui; Qian, Feng; Martin, Erika G
To estimate the programmatic costs of partner services for HIV, syphilis, gonorrhea, and chlamydial infection. New York State and local health departments conducting partner services activities in 2014. A cost analysis estimated, from the state perspective, total program costs and cost per case assignment, patient interview, partner notification, and disease-specific key performance indicator. Data came from contracts, a time study of staff effort, and statewide surveillance systems. Disease-specific costs per case assignment (mean: $580; range: $502-$1,111), patient interview ($703; $608-$1,609), partner notification ($1,169; $950-$1,936), and key performance indicator ($2,697; $1,666-$20,255) varied across diseases. Most costs (79 percent) were devoted to gonorrhea and chlamydial infection investigations. Cost analysis complements cost-effectiveness analysis in evaluating program performance and guiding improvements. © Health Research and Educational Trust.
Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry
Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus
Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both...
Fernandes, Juliana Folloni; Kerbauy, Fabio Rodrigues; Ribeiro, Andreza Alice Feitosa; Kutner, Jose Mauro; Camargo, Luis Fernando Aranha; Stape, Adalberto; Troster, Eduardo Juan; Zamperlini-Netto, Gabriele; Azambuja, Alessandra Milani Prandini de; Carvalho, Bruna; Dorna, Mayra de Barros; Vilela, Marluce Dos Santos; Jacob, Cristina Miuki Abe; Costa-Carvalho, Beatriz Tavares; Cunha, Jose Marcos; Carneiro-Sampaio, Magda Maria; Hamerschlak, Nelson
To report the experience of a tertiary care hospital with allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies. Seven pediatric patients with primary immunodeficiencies (severe combined immunodeficiency: n = 2; combined immunodeficiency: n = 1; chronic granulomatous disease: n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1) who underwent eight hematopoietic stem cell transplants in a single center, from 2007 to 2010, were studied. Two patients received transplants from HLA-identical siblings; the other six transplants were done with unrelated donors (bone marrow: n = 1; cord blood: n = 5). All patients had pre-existing infections before hematopoietic stem cell transplants. One patient received only anti-thymocyte globulin prior to transplant, three transplants were done with reduced intensity conditioning regimens and four transplants were done after myeloablative therapy. Two patients were not evaluated for engraftment due to early death. Three patients engrafted, two had primary graft failure and one received a second transplant with posterior engraftment. Two patients died of regimen related toxicity (hepatic sinusoidal obstruction syndrome); one patient died of progressive respiratory failure due to Parainfluenza infection present prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. Patients' status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.
Macías, Juan; Mancebo, María; Merino, Dolores; Téllez, Francisco; Montes-Ramírez, M Luisa; Pulido, Federico; Rivero-Juárez, Antonio; Raffo, Miguel; Pérez-Pérez, Montserrat; Merchante, Nicolás; Cotarelo, Manuel; Pineda, Juan A
Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. NCT01900015. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Abbott, Jordan K; Gelfand, Erwin W
Common variable immunodeficiency (CVID) refers to a grouping of antibody deficiencies that lack a more specific genetic or phenotypic classification. It is the immunodeficiency classification with the greatest number of constituents, likely because of the numerous ways in which antibody production can be impaired and the frequency in which antibody production becomes impaired in human beings. CVID comprises a heterogeneous group of rare diseases. Consequently, CVID presents a significant challenge for researchers and clinicians. Despite these difficulties, both our understanding of and ability to manage this grouping of complex immune diseases has advanced significantly over the past 60 years. Copyright © 2015 Elsevier Inc. All rights reserved.
Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent
Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555
Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.
Patick, A K; Boritzki, T J; Bloom, L A
Nelfinavir mesylate (formerly AG1343) is a potent and selective, nonpeptidic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that was discovered by protein structure-based design methodologies. We evaluated the antiviral and cytotoxic effects of two-drug combinations of nelfinavir with the clinically approved antiretroviral therapeutics zidovudine (ZDV), lamivudine (3TC), dideoxycytidine (ddC; zalcitabine), stavudine (d4T), didanosine (ddI), indinavir, saquinavir, and ritonavir and a three-drug combination of nelfinavir with ZDV and 3TC against an acute HIV-1 strain RF infection of CEM-SS cells in vitro. Quantitative assessment of drug interaction was evaluated by a universal response surface approach (W. R. Greco, G. Bravo, and J. C. Parsons, Pharm. Rev. 47:331-385, 1995) and by the method of M. N. Prichard and C. Shipman (Antiviral Res. 14:181-206, 1990). Both analytical methods yielded similar results and showed that the two-drug combinations of nelfinavir with the reverse transcriptase inhibitors ZDV, 3TC, ddI, d4T, and ddC and the three-drug combination with ZDV and 3TC resulted in additive to statistically significant synergistic interactions. In a similar manner, the combination of nelfinavir with the three protease inhibitors resulted in additive (ritonavir and saquinavir) to slightly antagonistic (indinavir) interactions. In all combinations, minimal cellular cytotoxicity was observed with any drug alone and in combination. These results suggest that administration of combinations of the appropriate doses of nelfinavir with other currently approved antiretroviral therapeutic agents in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity.
Jolles, S; Orange, J S; Gardulf, A; Stein, M R; Shapiro, R; Borte, M; Berger, M
Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion-centre administration, and the use of self- or health-professional-administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self-infusion regimens, however, require independence and self-reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self-administer or a lack of self-reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health-related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed. © 2014 British Society for Immunology.
Full Text Available Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11, Chediak-Higashi syndrome (n=2, leukocyte adhesion deficiency (n=2, MHC class 2 deficiency (n=2, chronic granulomatous syndrome (n=2, hemophagocytic lymphohistiocytosis (n=1, Wiskott-Aldrich syndrome (n=1, and Omenn syndrome (n=1. Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.
Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül
Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.
C.L. Mulder (Niels)
textabstractSubjects who have tested positive for the presence of antibodies against Human Immunodeficiency Virus Type I (further abbreviated as HIV), have to live with a lifethreatening infection. At present, no definite medical cure is available that prevents progression of HIV infection.
Human immunodeficiency virus (HIV) infection is increasing world-wide and highly active antiretroviral treatment ... Hospital with urethral catheter in situ and having failed medical therapy, he opted for transurethral ... endoscopic visualization of operation field, the .... percutaneous exposure: Centers for Disease Control and.
Gu, Yian; Nieves, Jeri W; Stern, Yaakov; Luchsinger, Jose A; Scarmeas, Nikolaos
To assess the association between food combination and Alzheimer disease (AD) risk. Because foods are not consumed in isolation, dietary pattern (DP) analysis of food combination, taking into account the interactions among food components, may offer methodological advantages. Prospective cohort study. Northern Manhattan, New York, New York. Two thousand one hundred forty-eight community-based elderly subjects (aged > or = 65 years) without dementia in New York provided dietary information and were prospectively evaluated with the same standardized neurological and neuropsychological measures approximately every 1.5 years. Using reduced rank regression, we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients: saturated fatty acids, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, vitamin B(12), and folate. The associations of reduced rank regression-derived DPs with AD risk were then examined using a Cox proportional hazards model. Main Outcome Measure Incident AD risk. Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a DP strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter. Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk.
Full Text Available Pyoderma vegetans (PV is a rare inflammatory disorder characterized by vegetating pustules and plaques affecting the skin and mucosal membranes. It is believed that this entity is mostly associated with inflammatory bowel disease (IBD, chronic malnutrition, human immunodeficiency virus (HIV, malignancies, and other immunocompromised states. Pyoderma vegetans occurs more commonly in young and middle-aged adults. There is no sex predilection for this entity. The lesions could heal spontaneously, but usually recur and become chronic. Our patient was an 11-year-old girl suspected to have primary combined immunodeficiency complicated by chronic recurrent vegetating pustular lesions on the face and postauricular area since one year of age. The histological features of the lesions were consistent with pyoderma vegetans. This is the first case of PV beginning from early infancy in the setting of primary immunodeficiency and in an unusual location.
Full Text Available Primary antibody deficiencies represent the most frequent genetic diseases of the immune system and the first to be recognized along immunology history. The antibodies were recognized as part of the humoral immune system long ago, and after immunoglobulin discovery, the first antibody immunodeficiency were recognized and named as “agammaglobulinemia”, followed by the common variable immunodeficiency and the hyper-IgM syndrome. The following discoveries in immunology history made possible the understanding of these pathologies, for example: the discoveries of B cells, pre-B cells, the signaling pathway directed by the antigen receptor and many other cellular and molecular mechanisms. Primary antibody deficiencies have been studied for a long time and the discoveries of new syndromes have been helpful in the understanding of immunological mechanisms that take place in our organism. Then, this manuscript pretends to review the relevant findings in the history of immunology, focused on the B cells and the connection with the description of representative clinical entities of primary antibody deficiencies. The aim of this manuscript is to show to the reader that the generation of scientific knowledge has a direct application in the understanding of the molecular mechanisms that are affected in these diseases.
Adriana Almeida de Jesus
Pediatric Rheumatology Unit. A retrospective evaluation was performed in patients that presented arthritis as the first clinical manifestation of immunodeficiency. The humoral immunodeficiencies were classified into selective IgA deficiency, hypogammaglobulinemia and IgG subclass deficiency. RESULTS: Eleven patients (0.2% had primary immunodeficiency: selective IgA deficiency occurred in 8, common variable immunodeficiency in two, and IgG subclass deficiency in one. Five of the 11 patients had an acute arthritis and six patients a chronic nonerosive arthritis (JIA-like. From the 253 JIA patients evaluated, 70 had IgA level evaluation done and 6 (8.5% presented complete IgA deficiency (serum IgA < 7 mg/dl (JIA-like. From the 45 JSLE patients with IgA levels evaluated, 3 (6.6% had selective IgA deficiency diagnosis. CONCLUSION: The present study showed a low prevalence of humoral immunodeficiency in patients with rheumatic diseases. However, this association suggests that similar defects in immune response could be related to both diseases and that prospective studies are needed to elucidate this hypothesis.
Wu, Eveline Y. [University of North Carolina at Chapel Hill, Department of Pediatrics, Chapel Hill, NC (United States); Ehrlich, Lauren [Yale School of Medicine, Department of Diagnostic Radiology, New Haven, CT (United States); Handly, Brian [University of North Carolina at Chapel Hill, Department of Radiology, Chapel Hill, NC (United States); Frush, Donald P. [Duke University Medical Center, Division of Pediatric Radiology, Durham, NC (United States); Buckley, Rebecca H. [Duke University Medical Center, Department of Pediatrics, Durham, NC (United States); Duke University School of Medicine, Department of Immunology, Durham, NC (United States)
Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders. (orig.)
Gu, Qiu-Hua; Jia, Xiao-Yu; Hu, Shui-Yi; Wang, Su-Xia; Zou, Wan-Zhong; Cui, Zhao; Zhao, Ming-Hui
Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Juliana Folloni Fernandes
Full Text Available Objective: To report the experience of a tertiary care hospital withallogeneic hematopoietic stem cell transplantation in children withprimary immunodeficiencies. Methods: Seven patients with primaryimmunodeficiencies (severe combined immunodeficiency: n = 2;combined immunodeficiency: n = 1; chronic granulomatous disease:n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1who underwent eight hematopoietic stem cell transplants (HSCTin a single center, from 2007 to 2010, were studied. Results: Twopatients received transplants from HLA-identical siblings; the othersix transplants were done with unrelated donors (bone marrow: n= 1; cord blood: n = 5. All patients had pre-existing infectionsbefore hematopoietic stem cell transplants. One patient receivedonly anti-thymocyte globulin prior to transplant, three transplantswere done with reduced intensity conditioning regimens and fourtransplants were done after myeloablative therapy. Two patientswere not evaluable for engraftment due to early death. Three patientsengrafted, two had primary graft failure and one received a secondtransplant with posterior engraftment. Two patients died of regimenrelated toxicity (hepatic sinusoidal obstruction syndrome; one patient died of progressive respiratory failure due to Parainfluenza infection diagnosed prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. Conclusion: Patients’ status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.
Full Text Available The incidence and prevalence of human immunodeficiency virus (HIV infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.
Preyas J Vaidya
Full Text Available Bleomycin is a cytostatic drug commonly employed in the treatment of Hodgkin's disease, seminomas, and choriocarcinoma. Bleomycin may induce a chronic pulmonary inflammation that may progress to fibrosis. So far, only corticosteroids have been used in the treatment of bleomycin-induced lung disease with variable results. Pirfenidone is an antifibrotic drug that has been approved for the treatment of idiopathic pulmonary fibrosis. We report two cases of bleomycin-induced lung disease treated successfully with pirfenidone and oral corticosteroids.
Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187
Full Text Available Primary immunodeficiency diseases (PIDs are a group of rare, chronic disorders with deficient or malfunctioning immune system. It commonly affects the hematopoietic system, with skin the second most affected organ. Skin involvement is observed in half of pediatric PID cases and often precedes the final diagnosis. Skin infections and eczemas are the two most common manifestations in PID. Skin manifestations associated with PIDs can be of infectious and noninfectious causes. Common noninfectious causes are eczema, erythroderma, cutaneous granulomas, dysplasia, vasculitis, and telangiectasia. It is important to be aware of skin manifestations in pediatric patients as early detection of PID may aid in the management of serious immunologic conditions and prevent associated morbidity and mortality.
Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy.
Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V; Iser, David; Sasadeusz, Joe; Lewin, Sharon R
Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.
M Elicer, Isabel; Byrd, Desiree; Clark, Uraina S; Morgello, Susan; Robinson-Papp, Jessica
HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.
Full Text Available Primary immunodeficiency disorders (PIDs are a group of disorders affecting the capability to fight against infection. These include defects in T cells and B cells affecting cell-mediated and humoral immunity, respectively, combined humoral and cell-mediated immunodeficiency, defects in phagocytosis, complement defects, and defects in cytokine or cytokine signalling pathways which are detrimental for immune function. Depending upon the type and severity, age at onset of symptoms can vary from neonatal period to late childhood. Clinically, this group of disorders can involve any organ system of an individual such as respiratory system, gastrointestinal system, skin and mucous membrane, bone and joints, endocrine organs, and nervous system. Common dermatological manifestations include eczema, warts, molluscum contagiosum, mucocutaneous candidiasis, recurrent nonhealing ulcers, skin abscesses, erythroderma, petechiae, and nail changes. The common skin manifestations of various PIDs include eczema (seen in Wiskott–Aldrich syndrome and autosomal dominant hyper IgE syndrome; erythroderma (in Omen syndrome; viral warts or molluscum contagiosum (in autosomal recessive hyper IgE syndrome; chronic mucocutaneous candidiasis (in hyper IgE syndrome, autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome, Th17 cell defects; recurrent nonhealing ulcers (in leucocyte adhesion defect; skin abscesses (in antibody defects, hyper IgE syndrome, and chronic granulomatous disease; petechial or purpuric spots (in Wiskott–Aldrich syndrome.
Mohammadi, Hakimeh; Bienzle, Dorothee
Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.
Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir
In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Kotler, Donald P
Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.
Koeijer, A.A. de
To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the
Ducancelle, Alexandra; Leroy, Vincent; Vergniol, Julien; Sturm, Nathalie; Le Bail, Brigitte; Zarski, Jean Pierre; Nguyen Khac, Eric; Salmon, Dominique; de Ledinghen, Victor; Calès, Paul
International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
Full Text Available The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-γ production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.
Bruno M. Teixeira
Full Text Available The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species. Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV causes an immune system disease in domestic cats (Felis catus involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs in South America.
Teixeira, Bruno M; Hagiwara, Mitika K; Cruz, Juliano C M; Hosie, Margaret J
The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.
The regenerative ability of haemopoietic organs during combined radiation injuries has not been adequately investigated. Interactions among individual factors can critically influence the processes involved in haemopoietic recovery. An overview of radiation injuries is given, and a concept towards a hypothetical mode of action at the cellular level is presented. The influence which interacting factors can have on the concentration of pluripotential haemopoietic stem cells is demonstrated by results from an initial experiment. The importance of synergistic and antagonistic reactions is emphasised and commented upon. (orig.) [de
Comparison between the Framingham and prospective cardiovascular of Münster scores for risk assessment of coronary heart disease in human immunodeficiency virus-positive patients in Pernambuco, Brazil.
Barros, Zoraya Medeiros; de Alencar Ximenes, Ricardo Arraes; Miranda-Filho, Demócrito Barros; de Albuquerque, Maria de Fátima Pessoa Militão; Melo, Heloísa Ramos Lacerda; Carvalho, Erico Higino; Gelenske, Thais; Diniz, George; Bandeira, Francisco
The Framingham score is used in most studies on human immunodeficiency virus (HIV)-positive patients to estimate the risk for coronary heart disease; however, it may have some limitations for detecting risk among these individuals. The aim of this study was to evaluate the agreement between the Framingham and Prospective Cardiovascular of Münster (PROCAM) scores among HIV-positive individuals and to investigate the factors associated with disagreement between the two scores. A cross-sectional study was conducted in a population of HIV/acquired immunodeficiency syndrome (AIDS) patients attending the outpatient's clinics of two reference centers for HIV/AIDS in Pernambuco, Brazil. Agreement between the Framingham and PROCAM scores was evaluated using the kappa index. From this analysis, a variable called "disagreement between scores" was created, and univariate and multivariate analysis were performed to investigate the factors associated with this variable. The prevalence of low, moderate, and high risk were, respectively, 78.7%, 13.5%, and 7.8% by Framingham score and 88.5%, 4.3%, and 7.2% by PROCAM (kappa = 0.64, P ≤ 0.0001). Agreement in the subgroup with metabolic syndrome by the International Diabetes Federation (IDF) (kappa = 0.51, P ≤ 0.0001) and the National Cholesterol Education Program (NCEP) (kappa = 0.59, P ≤ 0.0001) criteria was moderate. The Framingham score identified greater proportion of women with moderate risk. Factors independently associated with disagreement were: smoking, sex, age, low-density lipoprotein cholesterol, diastolic blood pressure, and metabolic syndrome. There was a good agreement between the Framingham and PROCAM scores in HIV-positive patients, but a higher proportion of moderate-high risk was identified by the Framingham score. This disagreement should be evaluated in cohort studies to observe clinical outcomes over the course of time.
Full Text Available Human immunodeficiency virus (HIV endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.
Yu, Hui; Zhang, Victor Wei; Stray-Pedersen, Asbjørg; Hanson, Imelda Celine; Forbes, Lisa R; de la Morena, M Teresa; Chinn, Ivan K; Gorman, Elizabeth; Mendelsohn, Nancy J; Pozos, Tamara; Wiszniewski, Wojciech; Nicholas, Sarah K; Yates, Anne B; Moore, Lindsey E; Berge, Knut Erik; Sorte, Hanne; Bayer, Diana K; ALZahrani, Daifulah; Geha, Raif S; Feng, Yanming; Wang, Guoli; Orange, Jordan S; Lupski, James R; Wang, Jing; Wong, Lee-Jun
Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management. We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting. The target gene capture/NGS assay provides an average read depth of approximately 1000×. The deep coverage facilitates simultaneous detection of single nucleotide variants and exonic copy number variants in one comprehensive assessment. Exons with insufficient coverage (diagnostic yield of severe primary immunodeficiency. Establishing a molecular diagnosis enables early immune reconstitution through prompt therapeutic intervention and guides management for improved long-term quality of life. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
U H Okafor
Full Text Available Since the emergence of acquired immune deficiency syndrome (AIDS about three decades ago, several renal disorders have been reported as common complications of human immunodeficiency virus (HIV infection. These renal disorders result from diverse etiologies. The aim of this cross-sectional study was to determine the prevalence and clinical and laboratory characteristics of anti-retroviral-naοve HIV-infected patients with impaired kidney disorder in South-South Nigeria. This study was conducted on patients presenting at the University of Benin Teaching Hospital, Benin City in South-South Nigeria for six months. The patients′ demographic data and clinical, hematological and biochemical parameters were assessed. Their glomerular filtration rate (GFR was calculated and the protein excretion was assessed from the protein- creatinine ratio. Data were analyzed using statistical software program SPSS version 15.0. Threehundred and eighty-three patients with a mean age of 35.39 ± 8.78 years and a male: female ratio of 1:1 were studied; 53.3% had evidence of kidney disorder. The main clinical features in patients with kidney disorder were evidence of fluid retention, urinary symptoms, pallor and encephalopathy. The mean systolic and diastolic blood pressures were 115.33 ± 17.17 and 72.33 ± 14.31 mm Hg, respectively. The mean estimated GFR was 52.5 mL/min/1.73 m 2 . Patients with kidney disorder had higher proteinuria (P = 0.001, lower mean CD4 cell count and packed cell volume (P = 0.019 and 0.001, respectively. Kidney disorder is a common complication in HIV-infected patients, and they have clinical and laboratory anomalies. Screening of HIV/AIDS patients at the time of diagnosis will facilitate early diagnosis of kidney disorders in them.
Bright, P; Grigoriadou, S; Kamperidis, P; Buckland, M; Hickey, A; Longhurst, H J
Common variable immunodeficiency (CVID) is the most common severe primary immunodeficiency, but the pathology of this condition is poorly understood. CVID involves a defect in the production of immunoglobulin from B cells, with a subsequent predisposition to infections. Approximately 10–20% of cases are inherited, but even in families with a genetic defect the penetrance is far from complete. A classification system for CVID has been suggested (EUROclass) based on B cell immunophenotyping, but it has not been shown that altered B cell immunophenotype is not a consequence of the complications and treatment of CVID. This study compares the EUROclass B cell immunophenotype of CVID patients (n = 30) with suitable disease controls with bronchiectasis (n = 11), granulomatous disease (Crohn's disease) (n = 9) and neurological patients on immunoglobulin treatment (n = 6). The results of this study correlate with previous literature, that alterations in B cell immunophenotype are associated strongly with CVID. Interestingly, three of the 11 bronchiectasis patients without known immunodeficiency had an altered B cell immunophenotype, suggesting the possibility of undiagnosed immunodeficiency, or that bronchiectasis may cause a secondary alteration in B cell immunophenotype. This study showed a significant difference in B cell immunophenotype between CVID patients compared to disease control groups of granulomatous disease and immunoglobulin treatment. This suggests that granulomatous disease (in Crohn's disease) and immunoglobulin treatment (for chronic neurological conditions) are not causal of an altered B cell immunophenotype in these control populations. PMID:23286946
Full Text Available The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata, are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies.
Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa
Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.
Feldman, Robert L; Nickell, Kent
...)/acquired immunodeficiency syndrome. With the arrival of avian influenza in Africa, the potential exists that some of those soldiers might also become infected with H5N1, the virus responsible for the disease...
Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.
Bruyand, Mathias; Thiébaut, Rodolphe; Lawson-Ayayi, Sylvie; Joly, Pierre; Sasco, Annie Jeanne; Mercié, Patrick; Pellegrin, Jean Luc; Neau, Didier; Dabis, François; Morlat, Philippe; Chêne, Geneviève; Bonnet, Fabrice
Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.
Bajic, Vladimir B.
The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer\\'s Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent, including an inhibitor of TLR4/MD-2/CD14, nAChR agonist, Resatorvid, Curcumin, Tilorone or a Tilorone analog, or a combination thereof.
Obregon, R.; Lynch, D.A.; Cink, T.M.; Newell, J.D.; Kirkpatrick, C.
This paper reviews the chest radiographs and high-resolution CT (HRCT) scans in patients with immunodeficiency disorders and define the role of HRCT. Thirty-three cases were retrospectively graded according to the consensus of two radiologists. Patients with HIV seropositivity and asthma were excluded. HRCT was performed in 12 cases with standard techniques. Diagnoses included common variable hypogammaglobulinemia (n = 19), X-linked agammaglobulinemia (n = 4), chronic mucocutaneous candidiasis (n = 4), and selective immunoglobulin g deficiencies (n = 2). Chest radiographs showed bronchiectasis in 11 of 33 cases with a predominant lower lobe distribution (82%). Nodules were present in six cases and mucus plugs in four cases. HRCT showed bronchiectasis in nine of 12 cases; in five of these nine cases, bronchiectasis was not apparent on chest radiographs. Other HRCT findings included segmental air trapping (four of 12), mucus plugs (three of 12), hazy consolidation (four of 12), nodules (five of 12), and bronchiolectasis (two of 12). Therapy was altered in seven of 12 cases in which HRCT was performed. Most pertinent to clinical management were the presence of a thymoma (n = 1) and severe focal of diffuse bronchiectasis
Most patients we care for today suffer from more than one chronic disease, and multimorbidity is a rapidly growing challenge. Concomitant cardiovascular disease, renal dysfunction and diabetes represent a large proportion of all patients in cardiology, nephrology and diabetology. These entities commonly overlap due to their negative effects on vascular function and an accelerated atherosclerosis progression. At the same time, a progressive subspecialisation has caused the cardiologist to treat 'only' the heart, nephrologists 'only' the kidneys and endocrinologists' 'only' diabetes. Studies and guidelines follow the same pattern. This often requires patients to visit specialists for each field, with a risk of both under-diagnosis and under-treatment. From the patient's perspective, there is a great need for coordination and facilitation of the care, not only to reduce disease progression but also to improve quality of life. Person-centred integrated clinics for patients with cardiovascular disease, renal dysfunction and diabetes are a promising approach for complex chronic disease management.
Kanao, Megumi; Kanda, Hirotsugu; Huang, Wan; Liu, Shue; Yi, Hyun; Candiotti, Keith A; Lubarsky, David A; Levitt, Roy C; Hao, Shuanglin
Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPβ was tested using immunohistochemistry. In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the
Antigen Loading (e.g., Glutamic Acid Decarboxylase 65 of Tolerogenic DCs (tolDCs Reduces Their Capacity to Prevent Diabetes in the Non-Obese Diabetes (NOD-Severe Combined Immunodeficiency Model of Adoptive Cotransfer of Diabetes As Well As in NOD Mice
David P. Funda
Full Text Available Tolerogenic DCs (tolDCs are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D. T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65, that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD-severe combined immunodeficiency (NOD-SCID recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein—ovalbumin (OVA. The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. application. These data document that mechanisms by which tol
Hourihane, J.; Hodges, E.; Smith, J.; Keefe, M.; Jones, A.; Connett, G.
A sister (aged 6 years) and brother (aged 8 years) presented four months apart with severe molluscum contagiosum. Both children demonstrated clinical and laboratory evidence of combined immunodeficiency. The extent of skin involvement by molluscum contagiosum precluded conventional treatment as well as intralesional interferon α (IFNα). Both subjects responded well to subcutaneous IFNα.
Treise, Irina; Huber, Eva M.; Klein-Rodewald, Tanja
By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results...
Leichliter, Jami S; Lewis, David A; Sternberg, Maya; Habel, Melissa A; Paz-Bailey, Gabriela
Episodic acyclovir therapy has been added to genital ulcer disease (GUD) syndromic management guidelines in several sub-Saharan African countries with human immunodeficiency virus (HIV) epidemics. We examined the correlates of health care seeking in men with GUD and its relationship to HIV-1 and herpes simplex virus type 2 outcomes. Men with GUD (n = 615) were recruited from primary health care clinics in Gauteng province, South Africa for a randomized controlled trial of episodic acyclovir therapy. We used baseline survey and sexually transmitted infection/HIV-testing data to examine delay in health care seeking (defined as time from ulcer recognition to baseline study visit). Median delay in health care seeking for GUD was 5 days, and one-quarter of men had previously sought care for the current ulcer. Previous care seekers were older, had more episodes of ulceration in the past year, and were more likely to test seropositive for HIV-1 and HSV-2. Delay in health care seeking was significantly associated with age, education level, and sex during the ulceration episode. Delays in care seeking were related to poorer HIV-1 outcomes; these findings were valid after controlling for advanced HIV. Interventions to help shorten the duration between ulcer recognition and health care seeking for men with GUD are needed.
Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group
Dubé, M. P.; Sprecher, D.; Henry, W. K.; Aberg, J. A.; Torriani, F. J.; Hodis, H. N.; Schouten, J. [=Judith; Levin, J.; Myers, G.; Zackin, R.; Nevin, T.; Currier, J. S.
Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy, These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the
ABSTRACT: The objective of this paper is to present a mathematical model formulated to investigate the dynamics of human immunodeficiency virus (HIV). The disease free equilibrium of the model was found to be locally and globally asymptotically stable. The endemic equilibrium point exists and it was discovered that the ...
The issue of homosexuality attracts global debate, given that this constitutes risk factor for sexually transmitted diseases. An exploration of socio-cultural, religious and sexual activities of lesbian, gay, bisexual, transgender and intersex sector would inform future Human Immunodeficiency Virus programming.
Background: Human Immunodeficiency Virus(HIV) and Hepatitis B Virus(HBV) infections are global viral diseases with various seroprevalence rates in different parts of the world. They share similar modes of transmission and are very important in Transfusion Medicine. Aim/Objective: To determine the level of awareness ...
van Leeuwen, E.; Prins, J. M.; Jurriaans, S.; Boer, K.; Reiss, P.; Repping, S.; van der Veen, F.
Human immunodeficiency virus type-1 (HIV-1) affects mostly men and women in their reproductive years. For those who have access to highly active antiretroviral therapy (HAART), the course of HIV-1 infection has shifted from a lethal to a chronic disease. As a result of this, many patients with HIV-1
Ettinger, M; Schreml, J; Wirsching, K; Berneburg, M; Schreml, S
Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs. © 2017 British Association of Dermatologists.
Crane, Megan; Iser, David; Lewin, Sharon R
Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.
Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu
Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.
Galicia, G; Betancourt, M A; Canales, L E; Cristerna, L
To determine the flowgram for the timely diagnosis of the immunodeficiencies congenital primary, based on the demonstrations otorrinolaringol recurrent chronicles to difficult control, with or without associated systemic diseases. Retrospective study, descriptive and observational that included patient with diagnostic of primary known immunodeficiency. They were checked the clinical files to know their evolution and medical treatment-surgical. They were found 10 patient with diagnostic of some primary immunodeficiency; this was made based on the infectious symptoms otolaryngal chronic recurrent to difficult control; they were six men and four women between the four and 36 years old. They were found the following immunodeficiencies: one of hyper-IgM, three by IgG, variable common three, a deficit with C3 of the complement, two of IgA more atopia. The chronicle sinusitis or recurrent and the otitis mean chronicle or recurrent can be the only demonstrations of a patient with primary immunodeficiency. The immunology evaluation must include, at least: hematic biometric completes with differential, seric levels of immunoglobulins, the same as subclass of IgG, C4 and C3 of the complement, response to immunization with proteins (diphtheria and tetanus), and polysaccharide antigens (pneumovax).
Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki
Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.
Pinto, Serge; Mancini, Laura; Jahanshahi, Marjan; Thornton, John S; Tripoliti, Elina; Yousry, Tarek A; Limousin, Patricia
Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task. Copyright © 2011 Movement Disorder Society.
Mutis, T; Rijn, R.S. van; Simonetti, E.R.; Aarts-Riemens, T.; Emmelot, M.E.; Bloois, L. van; Martens, A.; Verdonck, L.F.; Ebeling, S.B.
PURPOSE: Effective prevention of graft-versus-host disease (GvHD) is a major challenge to improve the safety of allogeneic stem cell transplantation for leukemia treatment. In murine transplantation models, administration of naturally occurring CD4+CD25+ regulatory T cells (Treg) can prevent GvHD.
Wehr, Claudia; Gennery, Andrew R.; Lindemans, Caroline; Schulz, Ansgar; Hoenig, Manfred; Marks, Reinhard; Recher, Mike; Gruhn, Bernd; Holbro, Andreas; Heijnen, Ingmar; Meyer, Deborah; Grigoleit, Goetz; Einsele, Hermann; Baumann, Ulrich; Witte, Thorsten; Sykora, Karl-Walter; Goldacker, Sigune; Regairaz, Lorena; Aksoylar, Serap; Ardeniz, Omur; Zecca, Marco; Zdziarski, Przemyslaw; Meyts, Isabelle; Matthes-Martin, Susanne; Imai, Kohsuke; Kamae, Chikako; Fielding, Adele; Seneviratne, Suranjith; Mahlaoui, Nizar; Slatter, Mary A.; Gungor, Tayfun; Arkwright, Peter D.; van Montfrans, JM; Sullivan, Kathleen E.; Grimbacher, Bodo; Cant, Andrew; Peter, Hans-Hartmut; Finke, Juergen; Gaspar, H. Bobby; Warnatz, Klaus; Rizzi, Marta
Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative
Hagleitner, M.M.; Lankester, A.; Maraschio, P.; Hulten, M.; Fryns, J.P.; Schuetz, C.; Gimelli, G.; Davies, E.G.; Gennery, A.R.; Belohradsky, B.H.; Groot, R. de; Gerritsen, E.J.; Mattina, T.; Howard, P.J.; Fasth, A.; Reisli, I.; Furthner, D.; Slatter, M.A.; Cant, A.J.; Cazzola, G.; Dijken, P.J. van; Deuren, M. van; Greef, J.C. de; Maarel, S.M. van der; Weemaes, C.M.R.
BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a
Bastian, Frank O
The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD.
Mortaz, Esmaeil; Tabarsi, Payam; Mansouri, Davod; Khosravi, Adnan; Garssen, Johan; Velayati, Aliakbar; Adcock, Ian M.
The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with
Peleška, Jan; Anger, Z.; Buchtela, David; Tomečková, Marie; Veselý, Arnošt; Zvárová, Jana
23 Suppl. 2, - (2005), s. 196 ISSN 0263-6352. [European Meeting on Hypertension /15./. 17.06.2005-21.06.2005, Milan] R&D Projects: GA AV ČR 1ET200300413 Institutional research plan: CEZ:AV0Z10300504 Keywords : European medical guidelines * formalization of combined guidelines Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery
Khanna, Reena; Bressler, Brian; Levesque, Barrett G.; Zou, Guangyong; Stitt, Larry W.; Greenberg, Gordon R.; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J.; Donner, Allan; Vandervoort, Margaret K.; Morris, Joan C.; Feagan, Brian G.; Anderson, Frank; Atkinson, Kenneth; Bacchus, Rahman; Berezny, Gary; Borthistle, Bruce; Buckley, Alan; Chiba, Naoki; Cockeram, Alan; Elkashab, Magdy; Fashir, Baroudi; Gray, James; Hemphill, Douglas; Hoare, Connie; Holland, Stephen; Hurowitz, Eric; Kaal, Nuri; Laflamme, Pierre; Borromee, Saint-Charles; Lau, Helena; McMullen, William; Memiche, Reshat; Menon, Krishna; Miller, D. Alexander; O'Hara, William; Oravec, Michael; Penner, Robert; Petrunia, Denis; Pluta, Henryk; Prabhu, Umesh; Prest, Marcia; Shaaban, Hani; Sheppard, Duane; Shulman, Scott
Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of
Full Text Available Background: Frequent infections is among the most frequent clinical dilemmas for primary care physicians. Immunodeficiency disorders are a heterogeneous group of illnesses that predispose patients to the recurrent infections, autoimmunity and malignancies. The aim of this study was to evaluate the clinical and laboratory data collected for the final diagnosis of patients referred with recurrent infections and suspected immunodeficiency to a local immunodeficiency clinic. Methods: This epidemiological study was carried out between April 2010 and September 2012 at the Immunodeficiency Clinic of Mashhad. All patients with clinical manifestations of immunodeficiency who were referred to our clinic during this period of time were included in this study. 41 patients aged from 10 months to 51 years, were evaluated. Results: Forty one patients, aged between 10 months and 51 years were evaluated. Eleven patients had a primary immunodeficiency, four cases had a secondary immunodeficiency, in three patients an underlying structural disease were found, eight patients were predisposed to recurrent infections as a result of allergies and finally, fifteen cases were found to be normal individuals. Discussion: Most patients with recurrent infection have a normal immune system. Allergic disorders are the most common predisposing factor to recurrent infection. However, as immunodeficiency disorders are potentially serious, early diagnosis can improve the quality of life and outcome and prevent severe sequels in future.
Flaminio, M Julia B F; LaCombe, Veronique; Kohn, Catherine W; Antczak, Douglas F
A 12-year-old Quarter Horse mare that was nonresponsive to medical treatment was evaluated for chronic respiratory disease and hepatobiliary disease. Serum immunoglobulin concentrations were measured by use of radial immunodiffusion that revealed trace to nondetectable concentrations of IgG, IgG(T), IgM, and IgA. Use of serum protein electrophoresis confirmed agammaglobulinemia by the absence of the expected peak in the gamma region. In addition, vaccination with tetanus toxoid did not result in specific immunoglobulin production. Flow cytometric analysis of blood lymphocyte subpopulations revealed the absence of B cells in blood. Immunohistochemical analysis of tissue sections revealed the absence of B lymphocytes in bone marrow and spleen, with occasional B cells in the peripheral lymph nodes. Blood lymphocyte proliferation assays revealed weak responses to pokeweed mitogen and no response to stimulation with lipopolysaccharide. Considering the age and sex of the horse, results of the immunologic tests suggested a diagnosis of common variable immunodeficiency.
Full Text Available The article is devoted to the combined pathology in childhood, namely a combination of bronchial asthma and gastroesophageal reflux disease. The authors highlighted the key theories of the disease etiopathogenesis under alternating environmental conditions. They also highlighted the results of their own studies.Key words: bronchial asthma, gastroesophageal reflux disease, children.
Bregenholt, S; Claesson, Mogens Helweg
Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transpla......Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall...
Tuberculose como doença definidora de síndrome da imunodeficiência adquirida: dez anos de evolução na Cidade do Rio de Janeiro Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil
Elizabeth Cristina Coelho Soares
Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodeficiency Syndrome database from 1993 to 2002. RESULTS: The expanded definition of a case of acquired immunodeficiency syndrome, implemented in 1998, resulted in a substantial increase in the number of reported cases of acquired immunodeficiency syndrome, especially of those defined by immunologic criteria. Among the cases of acquired immunodeficiency syndrome defined only by disease, esophageal candidiasis, in its various forms, remained the most common opportunistic infection present at the time the cases of acquired immunodeficiency syndrome were reported. Although Pneumocystis carinii pneumonia was the second leading opportunistic infection in most of the years evaluated, it was surpassed by tuberculosis in 2001. CONCLUSION: Despite the decreased numbers of cases of acquired immunodeficiency syndrome defined by disease, tuberculosis remains a significant acquired immunodeficiency syndrome-defining event, currently more common than P. carinii pneumonia and toxoplasmosis. This is probably due to the high rate of tuberculosis prevalence in the city.
Wheeler, David C; Waller, Lance A; Biek, Roman
The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.
Alcohol related hepatocellular liver injury was assessed using aspartate aminotransferase, and alanine aminotransferase levels. A combination of CAGE score ≥2 and De Ritis ratio ≥2 defined alcoholic liver disease (ALD). Human Immunodeficiency Virus (HIV), and viral hepatitis B and C serologies were evaluated in all ...
Full Text Available Initial immunodeficiencies are genetically conditioned defects of immune system; they are the basis for generalized infections including those induced by mycobacteria of tuberculosis complex. The lesions of skeleton in those patients are of different types depending on the kind of immunodeficiency. The article presents the results of clinical observation, conservative and surgical treatment of 12 children with mycobacterial lesions of skeleton on the ground different initial immunodeficiencies — severe combined immune deficiency, chronic granulematosis and insufficiency of interferon and interleukin 12.Key words: children, initial immunodeficiency, mycobacterial infection, bone lesions, surgical treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 60–64
Ceravolo, Ferdinando; Grisolia, Michele; Sestito, Simona; Falvo, Francesca; Moricca, Maria Teresa; Concolino, Daniela
The variants of neuronopathic Gaucher disease may be viewed as a clinical phenotypic continuum divided into acute and chronic forms. The chronic neuronopathic form of Gaucher disease is characterized by a later onset of neurological symptoms and protracted neurological and visceral involvement. The first-choice treatment for nonneuronopathic Gaucher disease is enzyme replacement therapy with recombinant analogues of the deficient human enzyme glucocerebrosidase. Enzyme replacement therapy has been shown to improve hematological and bone manifestations associated with Gaucher disease, but, as with most proteins, recombinant enzymes cannot cross the blood-brain barrier, which prevents effects on neurological manifestations. Substrate reduction therapy with miglustat (N-butyldeoxynojirimycin) inhibits glucosylceramide synthase, which catalyzes the first step in glycosphingolipid synthesis. Because miglustat can cross the blood-brain barrier, it has been suggested that, combined with enzyme replacement therapy, it might be effective in treating neurological symptoms in patients with neuronopathic Gaucher disease. We report observed effects of combined enzyme replacement therapy and substrate reduction therapy in a 7-year-old Caucasian boy with neuronopathic Gaucher disease who was homozygous for L444P mutations. He had received enzyme replacement therapy from the age of 18 months, and concomitant miglustat treatment was commenced, with dosing according to body surface area uptitrated over 1 month with dietary modifications when he reached the age of 30 months. He experienced mild diarrhea after commencing miglustat therapy, which decreased in frequency/severity over time. His splenomegaly was reduced, and his hematological values and plasma angiotensin-converting enzyme activity normalized. Plasma chitotriosidase also showed substantial and sustained decreases. After 5 years of combination therapy, the patient showed no signs of neurological impairment. This case
Rapid assessment of sexual behavior, drug use, human immunodeficiency virus, and sexually transmitted diseases in northern thai youth using audio-computer-assisted self-interviewing and noninvasive specimen collection.
van Griensven, F; Supawitkul, S; Kilmarx, P H; Limpakarnjanarat, K; Young, N L; Manopaiboon, C; Mock, P A; Korattana, S; Mastro, T D
Drug use, unwanted pregnancy, human immunodeficiency virus (HIV) infection, and sexually transmitted diseases are serious health problems among Thai youth. The gravity of these problems demands high-quality data to direct public health policy and prevention programs. Previous studies of stigmatized behaviors have been hampered by participation bias and underreporting. To evaluate sexual behavior, disease, and drug use, we used audio-computer-assisted self-interviewing (ACASI) and noninvasive specimen collection methods. We also evaluated effectiveness of these methods in minimizing participation bias and underreporting. In late 1999, students aged 15 to 21 years attending 3 vocational schools were invited to participate in a cross-sectional survey. Consenting students completed a classroom-based ACASI interview using a confidential code number system. Oral fluid specimens were tested for HIV antibodies, and urine was tested for chlamydial and gonococcal nucleic acids, methamphetamines, and opiates. Of 1736 invited students, 1725 (99%) agreed to participate. Of these, 48% of the male students and 43% of the female students reported ever having had sexual intercourse. Overall, the mean number of lifetime sexual partners was 4.6 among male participants (median: 2) and 2.8 among female participants (median: 1). Consistent use of condoms with steady partners was reported by 16% of male participants and 11% of female participants who had such partners. Of all male participants, 7% had ever paid for sex, 3% had ever sold sex, and 7% had ever been coerced to have sex. Of all female participants, 3% had ever sold sex and 21% had ever been coerced to have sex. Among women with a history of sexual intercourse, 27% reported at least 1 pregnancy. Of these pregnancies, 83% were terminated. Among those with sexual intercourse experience, the prevalence of HIV infection was 0.5%; of infection with Neisseria gonorrhoeae, 0.4%; and of infection with Chlamydia trachomatis, 5%. Twenty
Full Text Available The potential involvement of host microRNAs (miRNAs in HIV infection is well documented, and evidence suggests that HIV modulates and also dysregulates host miRNAs involved in maintaining the host innate immune system. Moreover, the dysregulation of host miRNAs by HIV also effectively interferes directly with the host gene expression. In this study, we have simultaneously evaluated the expression of host miRNAs in both CD4+ and CD8+ T-cells derived from HIV-positive (HIV+ individuals (viremic and aviremic individuals while receiving highly active antiretroviral therapy (HAART, therapy-naïve long-term non-progressors (LTNP, and HIV-negative (HIV– healthy controls. miRNAs were run on Affymetrix V2 chips, and the differential expression between HIV+ and HIV− samples, along with intergroup comparisons, was derived using PARTEK software, using an FDR of 5% and an adjusted p-value < 0.05. The miR-199a-5p was found to be HIV-specific and expressed in all HIV+ groups as opposed to HIV– controls. Moreover, these are the first studies to reveal clearly the highly discriminatory miRNAs at the level of the disease state, cell type, and HIV-specific miRNAs.
The extremity edema of advanced disease is a common, multifactorial feature, which impairs patients' activities and quality of life. The most frequently chosen management is based on combined decongestive physiotherapy or pharmacotherapy (with diuretics or steroids). Subcutaneous lymphatic drainage in refractory edema may decrease the swelling, prevent spontaneous lymphorrhea, but also increase the risk of infection. Safe and effective conservative management in diuretics-resistant edemas is lacking. The objective of this prospective, observational study was to assess the effectiveness and tolerability of combined physiotherapeutic and diuretic therapy in edemas refractory to parenteral diuretics. A group of 19 patients with advanced disease and severe bilateral leg edema resistant to parenteral diuretic therapy were treated for three days with a combination of multilayer short-stretch compression bandaging and furosemide in hypersaline intravenous infusion. A clinically meaningful decrease in mean limb volume (of 1.52 L; 20.6%; P performance status in any patient. Stable levels of blood pressure, laboratory kidney profile (potassium, sodium, creatinine clearance), and serum albumin were observed. Maintenance of the achieved results with a good compliance was seen during an informal follow-up at the hospice. The combination of compression therapy with hypersaline diuretics could be considered as a valuable option for refractory cases of limb edema in advanced disease. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
Xu Haiqing; Wu Bian
Objective: To investigate the clinical curative effects of 131 I therapy combined with low-dose lithium carbonate for Graves disease. Methods: Patients with Graves disease took lithium carbonate (250 mg, once per day) orally for 5 weeks. Then they were treated with 131 I (doses=3.15 MBq(80 uCi)/g, based on 60%-70% of the thyroid size). We kept track from 6 to 24 months (averaging 14 months) and classified the results into three: cured, improved or no effect. Results: After a single cycle of 131 I therapy combined with low-dose lithium carbonate, 106 patients with Graves disease were cured, 28 were improved and 8 saw no effects, respectively 74.6%, 19.7% and 5.6% among the 142 patients. We then treated 23 of them with another 131 I therapy (without lithium carbonate). 10 of such were cured (43.5%), 8 were improved (34.8%) and the other 5 saw no effects. Among all patients, hypothyroidism was observed from 25(17.6%), 6 months after the first 131 I therapy. Conclusions: Notable curative results were observed from 131 I therapy combined with low-dose lithium carbonate for Graves disease. Moreover, the dosage of 131 I was therefore decreased, which also lowered the toxicity response. (authors)
Ismed Setya Budi
Full Text Available The use of combination of specific endophytic in tidal swamps to control stem root disease as biological control agents has not been done. It is expected that this combination is able to continuously protect plants from pathogen interference. The research was carried out in type C tidal swamp in Banjar regency of South Kalimantan, from March to November 2011, temperature 29-32oC, and pH 4.0-5.5. The method used was Split Plot design. Biocontrol preparation for both types of endophytic was applied in seeds in 7 days after planting (DAP. Observation on high intensity and plant diseases of planting stage on tidal swamps (taradak, ampak and lacak was conducted. The results showed that there was a reduction of disease ranging from 58.70 to 87.29%. The application of combination of two biocontrol agents (T. viride PS-2.1 + P. fluorescent PS-4.8, (Fusarium non-pathogenic PS-1.5 + P. fluorescent PS-4.8 and (T. viride PS-2.1+ FNP PS-1.5 isolate gave the best inhibition result, reduced disease intensity, and increased plant height. The result of soil analysis before and after application of endophytic showed that there was an increase in soil fertility with the element addition of N, P, K and pH.
Full Text Available Visceral leishmaniasis (VL is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis.
Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X
Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson
Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng
Objective: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Methods: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. D...
Ting, Patricia T; Koo, John Y
Etanercept (Enbrel, Amgen, Thousand Oaks, CA), a soluble p75 tumor necrosis factor receptor:FC (TNFR:FC) fusion protein for plasma cytokines, specifically tumor necrosis factor-alpha (TNF-alpha), is used in the treatment of immune-mediated rheumatic diseases. To our knowledge, the use of etanercept in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is relatively uncommon. The main purpose of this short review is to examine the safety of etanercept in patients with HIV/AIDS. A Medline search was conducted using the keywords etanercept and HIV and/or AIDS for any published articles between 1966 to the present (September 2004). A case report, one case series, and one clinical trial pertained to the use of etanercept in HIV patients. No reports were found on the use of etanercept in AIDS. In addition, two case reports were found documenting the use of infliximab in HIV patients. Preliminary reports indicate that the administration of etanercept does not appear to increase the morbidity or mortality rates in HIV. The inhibition of TNF-alpha may actually improve the symptoms of HIV/AIDS-associated aphthous ulcers, cachexia, dementia, fatigue, and fever, as well as help manage concomitant rheumatic diseases and psoriasis. The use of etanercept shows promise for applications in disease management in patients with HIV/AIDS. Continued research efforts are necessary to establish the long-term safety and efficacy of etanercept and other biologic agents in this patient population.
Cole, Donald C; Govender, Nelesh P; Chakrabarti, Arunaloke; Sacarlal, Jahit; Denning, David W
More than 1·6 million people are estimated to die of fungal diseases each year, and about a billion people have cutaneous fungal infections. Fungal disease diagnosis requires a high level of clinical suspicion and specialised laboratory testing, in addition to culture, histopathology, and imaging expertise. Physicians with varied specialist training might see patients with fungal disease, yet it might remain unrecognised. Antifungal treatment is more complex than treatment for bacterial or most viral infections, and drug interactions are particularly problematic. Health systems linking diagnostic facilities with therapeutic expertise are typically fragmented, with major elements missing in thousands of secondary care and hospital settings globally. In this paper, the last in a Series of eight papers, we describe these limitations and share responses involving a combined health systems and public health framework illustrated through country examples from Mozambique, Kenya, India, and South Africa. We suggest a mainstreaming approach including greater integration of fungal diseases into existing HIV infection, tuberculosis infection, diabetes, chronic respiratory disease, and blindness health programmes; provision of enhanced laboratory capacity to detect fungal diseases with associated surveillance systems; procurement and distribution of low-cost, high-quality antifungal medicines; and concomitant integration of fungal disease into training of the health workforce. Copyright © 2017 Elsevier Ltd. All rights reserved.
Palmblad, Magnus; Torvik, Vetle I
Tropical medicine appeared as a distinct sub-discipline in the late nineteenth century, during a period of rapid European colonial expansion in Africa and Asia. After a dramatic drop after World War II, research on tropical diseases have received more attention and research funding in the twenty-first century. We used Apache Taverna to integrate Europe PMC and MapAffil web services, containing the spatiotemporal analysis workflow from a list of PubMed queries to a list of publication years and author affiliations geoparsed to latitudes and longitudes. The results could then be visualized in the Quantum Geographic Information System (QGIS). Our workflows automatically matched 253,277 affiliations to geographical coordinates for the first authors of 379,728 papers on tropical diseases in a single execution. The bibliometric analyses show how research output in tropical diseases follow major historical shifts in the twentieth century and renewed interest in and funding for tropical disease research in the twenty-first century. They show the effects of disease outbreaks, WHO eradication programs, vaccine developments, wars, refugee migrations, and peace treaties. Literature search and geoparsing web services can be combined in scientific workflows performing a complete spatiotemporal bibliometric analyses of research in tropical medicine. The workflows and datasets are freely available and can be used to reproduce or refine the analyses and test specific hypotheses or look into particular diseases or geographic regions. This work exceeds all previously published bibliometric analyses on tropical diseases in both scale and spatiotemporal range.
Mozharovskiy, V V; Tsyganov, A A; Mozharovskiy, K V; Tarasov, A A
To assess an effectiveness of surgical treatment of gastroesophageal reflux disease (GERD) combined with hiatal hernia (HH). The trial included 96 patients with GERD and HH who were divided into 2 groups. The principal difference between groups was the use of surgery in the main group and therapeutic treatment in the comparison group. The effectiveness of surgical treatment is superior to therapeutic treatment of GERD by more than 2.5 times. HH combined with GERD is an indication for surgical treatment. Fundoplication cuff should not lead to angular and rotational esophageal deformation. Nissen procedure in Donahue modification (Short Floppy Nissen) simulates optimally the geometry of esophago-gastric junction and His angle.
Budi, Ismed Setya; Mariana, Mariana
The use of combination of specific endophytic in tidal swamps to control stem root disease as biological control agents has not been done. It is expected that this combination is able to continuously protect plants from pathogen interference. The research was carried out in type C tidal swamp in Banjar regency of South Kalimantan, from March to November 2011, temperature 29-32oC, and pH 4.0-5.5. The method used was Split Plot design. Biocontrol preparation for both types of endophytic was ap...
Freitag, J.; Schmidt, H.; Otto, H.J.; Punrich, R.; Gunkel, H.; Mann, D.; Freitag, G.; Waigand, J.; Eger, H.; Zentralklinik fuer Herz- u. Lungenkrankheiten, Bad Berka; Akademie der Wissenschaften der DDR, Berlin-Buch. Zentralinstitut fuer Herz-Kreislaufforschung)
Cardiac computer tomography, echocardiography and radionuclide heart diagnosis are growing more and more important in cardiologic diagnostics. The value of the procedures was tested in 74 patients by combined application. Concordant morphologic findings could be obtained with echocardiography and cardiac computer tomography in the cases of chronic ischemic heart disease, cardiomyopathy and valvular heart diseases. Localized kinetic disturbances could be registered echocardiographically and by scintiscanning. The passableness of an aortocoronary bypass can be controlled first of all non-invasively by cardiac computer tomography. (author)
Schmidt, H.A.E.; Birk, W.; Michele, E.
Investigations on 106 patients with coronary artery disease were performed to improve the diagnosis of myocardial ischemia by combining myocardial scintigraphy and gated blood pool studies. The results show that it is possible to enhance the detection of coronary artery and to classify haemodynamic efficiency. In addition we found that in investigations performed on patients with arrhytmia and under stress conditions the 'hybrid-technique' is superior to the framemode acquisition method. (orig.) [de
Brodrick, H.T.; Thomas, A.C.; Van Tonder, A.J.; Terblanche, J.C.
The spoilage of strawberries under local market conditions was investigated. It was confirmed that the major losses are due to 'leak' disease caused by Rhizopus stolonifer (Ehr. ex Fr.) Lind. It was also established that further fruit losses in summer are due to anthracnose caused by the fungus Colletotrichum acutatum Simmonds. This is the first time that the latter pathogen has been isolated and identified and recognised as a problem on strawberries in South Africa. Studies with R. stolonifer in culture showed that 46 degrees Celsius for 20 min (the previous international standard heat treatment for fruit) was disappointing, while a treatment at 50 degrees Celsius for 10 min effectively inhibited spore germination. Irradiation studies with cultures of R. stolonifer and C. acutatum showed that a dose of 200 and 100 krad, respectively, resulted in excellent inhibition of spore germination. However, irradiating in nitrogen gas resulted in a tenfold reduction in the effectiveness of the irradiation treatments. The use of nitrogen during irradiation, therefore, cannot be considered, especially where an effective control of the fungal pathogens is desired. Investigations with different cultivars clearly demonstrated the synergistic effect on disease control obtained when combining heat and irradiation treatments. The combination treatment (moist heat at 50-52 degrees Celsius for 10 min plus 200 krad), besides effectively controlling both diseases in strawberries, did not adversely affect berry quality. In simulated transport tests it was shown that a minimal amount of berry softening did occur with this treatment, but this adverse effect was negligible compared with the beneficial effect obtained from disease control. In semi-commercial experiments it was shown that the combination heat and irradiation treatment effectively controlled spoilage diseases for a period of several days from picking, thus allowing sufficient time to market the fruit under local market
Civallero, Monica; Cosenza, Maria; Pozzi, Samantha; Sacchi, Stefano
JAK-2 dysregulation plays an important role as an oncogenic driver, and is thus a promising therapeutic target in hematological malignancies. Ruxolitinib is a pyrrolo[2.3-d]pyrimidine derivative with inhibitory activity against JAK1 and JAK2, moderate activity against TYK2, and minor activity against JAK3. Vorinostat is an HDAC inhibitor that reduces JAK-2 expression, thus affecting JAK-2 mRNA expression and increasing JAK-2 proteasomal deterioration. Here we hypothesized that the combination of ruxolitinib and vorinostat could have synergistic effects against hematological disease. We tested combinations of low doses of ruxolitinib and vorinostat in 12 cell lines, and observed highly synergistic cytotoxic action in six cell lines, which was maintained for up to 120 h in the presence of stromal cells. The sensitivity of the six cell lines may be explained by the broad effects of the drug combination, which can affect various targets. Treatment with the combination of ruxolitinib and vorinostat appeared to induce a possible reversal of the Warburg effect, with associated ROS production, apoptotic events, and growth inhibition. Decreased glucose metabolism may have markedly sensitized the six more susceptible cell lines to combined treatment. Therapeutic inhibition of the JAK/STAT pathway seems to offer substantial anti-tumor benefit, and combined therapy with ruxolitinib and vorinostat may represent a promising novel therapeutic modality for hematological neoplasms.
Lola C Hudson
Full Text Available Lola C Hudson1, Brenda A Colby1, Rick B Meeker21Department of Molecular Biosciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 2Department of Neurology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: Earlier studies suggested that the combination of alcohol use and immunodeficiency virus infection resulted in more severe neurologic disease than either condition individually. These deleterious interactions could be due to increased immune cell and virus trafficking or may result from interactions between ethanol and human immunodeficiency virus (HIV-associated toxicity within the brain. To determine the extent to which increased trafficking played a role, we examined the effect of ethanol on the migration of different peripheral blood mononuclear cell (PBMCs subsets across a brain endothelial cell monolayer. We utilized combinations of feline brain endothelial cells with astrocytes, and/or microglia with either acute exposure to 0.08 g/dL ethanol, a combination of ethanol and feline immunodeficiency virus (FIV, or FIV alone. Adherence of PBMCs to endothelium was increased in all combinations of cells with the addition of ethanol. Despite increased PBMC adhesion with ethanol treatment, transmigration of B cells, monocytes, CD4 T cells and CD8 T cells was not increased and was actually decreased in the presence of astrocytes. Expression of three common adhesion molecules, intercellular adhesion molecule-1 (ICAM1, ICAM2, and vascular cell adhesion molecule, was unchanged or slightly decreased by ethanol. This indicated that although adherence is increased by ethanol it is not due to an increased expression of adhesion molecules. RANTES, MIP1α, MIP1β, and MCP-1 mRNA expression was also studied in brain endothelial cells, astrocytes and microglia by reverse transcriptase-polymerase chain reaction. Ethanol treatment of astrocytes resulted in modest changes of
Mohanty, Madhu Chhanda; Madkaikar, Manisha Rajan; Desai, Mukesh; Taur, Prasad; Nalavade, Uma Prajwal; Sharma, Deepa Kailash; Gupta, Maya; Dalvi, Aparna; Shabrish, Snehal; Kulkarni, Manasi; Aluri, Jahnavi; Deshpande, Jagadish Mohanrao
Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.
Farmand, S; Baumann, U; von Bernuth, H; Borte, M; Foerster-Waldl, E; Franke, K; Habermehl, P; Kapaun, P; Klock, G; Liese, J; Marks, R; Müller, R; Nebe, T; Niehues, T; Schuster, V; Warnatz, K; Witte, T; Ehl, S; Schulze, I
Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI). The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011. The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined. © Georg Thieme Verlag KG Stuttgart · New York.
Shrot, Shai; Soudack, Michalle [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Tel Aviv University, Sackler School of Medicine, Tel Aviv (Israel); Barkai, Galia [Sheba Medical Center, Pediatric Infectious Diseases Unit, Safra Children' s Hospital, Tel-Hashomer (Israel); Ben-Shlush, Aviva [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel)
When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)
Thomas J. Anastasio
Full Text Available Like other neurodegenerative diseases, Alzheimer Disease (AD has a prominent inflammatory component mediated by brain microglia. Reducing microglial inflammation could potentially halt or at least slow the neurodegenerative process. A major challenge in the development of treatments targeting brain inflammation is the sheer complexity of the molecular mechanisms that determine whether microglia become inflammatory or take on a more neuroprotective phenotype. The process is highly multifactorial, raising the possibility that a multi-target/multi-drug strategy could be more effective than conventional monotherapy. This study takes a computational approach in finding combinations of approved drugs that are potentially more effective than single drugs in reducing microglial inflammation in AD. This novel approach exploits the distinct advantages of two different computer programming languages, one imperative and the other declarative. Existing programs written in both languages implement the same model of microglial behavior, and the input/output relationships of both programs agree with each other and with data on microglia over an extensive test battery. Here the imperative program is used efficiently to screen the model for the most efficacious combinations of 10 drugs, while the declarative program is used to analyze in detail the mechanisms of action of the most efficacious combinations. Of the 1024 possible drug combinations, the simulated screen identifies only 7 that are able to move simulated microglia at least 50% of the way from a neurotoxic to a neuroprotective phenotype. Subsequent analysis shows that of the 7 most efficacious combinations, 2 stand out as superior both in strength and reliability. The model offers many experimentally testable and therapeutically relevant predictions concerning effective drug combinations and their mechanisms of action.
Anastasio, Thomas J
Like other neurodegenerative diseases, Alzheimer Disease (AD) has a prominent inflammatory component mediated by brain microglia. Reducing microglial inflammation could potentially halt or at least slow the neurodegenerative process. A major challenge in the development of treatments targeting brain inflammation is the sheer complexity of the molecular mechanisms that determine whether microglia become inflammatory or take on a more neuroprotective phenotype. The process is highly multifactorial, raising the possibility that a multi-target/multi-drug strategy could be more effective than conventional monotherapy. This study takes a computational approach in finding combinations of approved drugs that are potentially more effective than single drugs in reducing microglial inflammation in AD. This novel approach exploits the distinct advantages of two different computer programming languages, one imperative and the other declarative. Existing programs written in both languages implement the same model of microglial behavior, and the input/output relationships of both programs agree with each other and with data on microglia over an extensive test battery. Here the imperative program is used efficiently to screen the model for the most efficacious combinations of 10 drugs, while the declarative program is used to analyze in detail the mechanisms of action of the most efficacious combinations. Of the 1024 possible drug combinations, the simulated screen identifies only 7 that are able to move simulated microglia at least 50% of the way from a neurotoxic to a neuroprotective phenotype. Subsequent analysis shows that of the 7 most efficacious combinations, 2 stand out as superior both in strength and reliability. The model offers many experimentally testable and therapeutically relevant predictions concerning effective drug combinations and their mechanisms of action.
Bouzas, R.; Migueles, Y.; Gomez, S.; Mallo, R.; Garcia-Tejedor, J. L.; Diaz Vega, M. J.
Combined CT Venography and Pulmonary Angiography was described in 1998 as a tool for diagnostic Thromboembolic Disease. The purpose is to relate our own experience with this technique in a population with suspected pulmonary embolism. 46 consecutive patients with suspected pulmonary embolism underwent combined CT Venography after Pulmonary CT Angiography to depict Deep Venous Thrombosis (DVT). CT Venography where obtained with a 3 minutes delay from injection, without additional intravenous contrast, from upper abdomen to fibular head. A prospective study from emergency reports where used. The reports where aimed by nine different radiologist at diary emergency room (images where not retrospective review). We report if a pulmonary embolus or deep venous thrombus or another alternative diagnostic where done. An endo luminal thrombus in any pulmonary arteries was assessed as a positive study for PE. A Thrombus in the leg veins or in an abdominal vein without diminished size of vein was assessed as an acute DVT. In those patients with a CT negative to Thromboembolic Disease was the clinician who decide if more proves where needed. Those patients without evidence in CT of Thromboembolic Disease where asked for symptoms related to the episode in a 3 months period after initial CT. Patients free of symptoms for 3 months without anticoagulation therapy where considered true negative for CT. CT shows Thromboembolic Disease in 23 of 46 patients. 21PE, 14 DVT 2 of 14 patients with DVT don't show PE, CT excluded thromboembolic disease in 23 patients and in 15 of those patients an alternative diagnostic was shown. In 22 of those 23 patients CT excluded correctly Thromboembolic Disease. One patient result in a false negative CT, Pulmonary Angiography of that patient shows us a subsegmentary embolus. (Author) 9 refs
Yew Ann Leong
Full Text Available Human immunodeficiency virus (HIV infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV. Identifying and eliminating the HIV reservoir will prevent viral rebound and cure HIV infection. In this review, we focus on a recently discovered HIV reservoir in a subset of CD4+ T cells called the follicular helper T (TFH cells. We describe the potential mechanisms for the emergence of reservoir in TFH cells, and the strategies to target and eliminate this viral reservoir.
Krejsgaard, Thorbjørn Frej; Ødum, Niels; Geisler, Carsten
Cutaneous T-cell lymphoma (CTCL) is the term for diseases characterized by primary accumulation of malignant T cells in the skin. Patients with the two predominant clinical forms of CTCL called mycosis fungoides (MF) and Sézary syndrome (SS) characteristically develop severe immunodeficiency duri...... in MF and SS and discuss the potential mechanisms driving the immunodeficiency.Leukemia advance online publication, 9 September 2011; doi:10.1038/leu.2011.237....
Coutinho, Thais; Goel, Kashish; Corrêa de Sá, Daniel
This study sought to assess the mortality risk of patients with coronary artery disease (CAD) based ona combination of body mass index (BMI) with measures of central obesity.......This study sought to assess the mortality risk of patients with coronary artery disease (CAD) based ona combination of body mass index (BMI) with measures of central obesity....
Siciliano, Antonio Alexandre de Oliveira; Melo, Alessandro Severo Alves de; Marchiori, Edson
The authors report two cases of bronchogenic carcinoma in patients with acquired immunodeficiency syndrome. The first patient, a ee-year-old male, developed a left hilar adenocarcinoma, with spleen and bilateral adrenal metastases. The disease progressed unfavourably, resulting in the patient's death in less than a month. The second patient, a 47-year-old male, developed a large mass in the left upper lobe, with invasion of the thoracic wall and destruction of adjacent ribs. The histopathologic study revealed a non-oat-cell carcinoma. Both patients received palliative treatment since diagnosis was established late in the course of the disease. Recent studies suggest an association between bronchogenic carcinoma and human immunodeficiency virus infection. However, an actual increase in the prevalence of bronchogenic carcinoma in HIV-positive patients remains controversial. (author)
Full Text Available Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi’s granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency.
Esther van de Vosse
To facilitate the analysis of variations identified by researchers around the world, databases have been set up that contain all reported MSMD patients and mutations (see for instance: www.lovd.nl/IL12RB1. Thus far, just over 400 patients have been reported worldwide with MSMD and this is probably only the tip of the iceberg. Also, other genes are still expected to be found to cause MSMD; no genes have been reported so far in which mutations specifically lead to susceptibility to tuberculosis.
Yang, X Y; Guo, C Y; Zhang, X; Zhong, Y Q; Tian, C
Objective: To investigate the curative effect of Deanxit combined with Shuganjieyu capsule on the treatment of refractory gastroesophageal reflux disease. Methods: A total of 125 patients with refractory gastroesophageal reflux disease who had failed in standard lansolazole capsule treatment in the Department of Gastroenterology, First People's Hospital of Neijiang were selected. According to the symptom scores and mood scores of gastroesophageal reflux disease, patients were randomly and double-blindly divided into five groups. Group A(Lansoprazole Capsules + Mosapride Citrate + Deanxit), B(Lansoprazole Capsules + Mosapride Citrate + Shuganjieyu capsule), C(Lansoprazole Capsules + Mosapride Citrate+ Deanxit + Shuganjieyu capsule) and D(Deanxit) groups are study groups, the other was control group (Lansoprazole Capsules + Mosapride Citrate). The scores of symptoms and mood were compared after 4 weeks and 8 weeks of treatment. Results: The clinical symptoms score, HAMA and HAMD scores were significantly lower in the all study groups in comparison to the control group after 4 weeks and 8 weeks therapy. The clinical symptoms score, HAMA and HAMD scores in group C were significantly lower than those in group A and B ( P 0.05). The HAMA and HAMD scores of group D were significantly higher than those of group A, B, C and control group, and the differences were statistically significant ( P gastroesophageal reflux disease, which can effectively improve the total treatment efficiency, reduce the symptom scores and mood scores of gastroesophageal reflux disease patients.
Liu, Bin; Jin, Min; Zeng, Pan
The identification of gene-phenotype relationships is very important for the treatment of human diseases. Studies have shown that genes causing the same or similar phenotypes tend to interact with each other in a protein-protein interaction (PPI) network. Thus, many identification methods based on the PPI network model have achieved good results. However, in the PPI network, some interactions between the proteins encoded by candidate gene and the proteins encoded by known disease genes are very weak. Therefore, some studies have combined the PPI network with other genomic information and reported good predictive performances. However, we believe that the results could be further improved. In this paper, we propose a new method that uses the semantic similarity between the candidate gene and known disease genes to set the initial probability vector of a random walk with a restart algorithm in a human PPI network. The effectiveness of our method was demonstrated by leave-one-out cross-validation, and the experimental results indicated that our method outperformed other methods. Additionally, our method can predict new causative genes of multifactor diseases, including Parkinson's disease, breast cancer and obesity. The top predictions were good and consistent with the findings in the literature, which further illustrates the effectiveness of our method. Copyright © 2015 Elsevier Inc. All rights reserved.
Chida, Yoichi; Vedhara, Kavita
There is a growing epidemiological literature focusing on the association between psychosocial stress and human immunodeficiency virus (HIV) disease progression or acquired immunodeficiency syndrome (AIDS), but inconsistent findings have been published. We aimed to quantify the association between adverse psychosocial factors and HIV disease progression. We searched Medline; PsycINFO; Web of Science; PubMed up to 19 January 2009, and included population studies with a prospective design that investigated associations between adverse psychosocial factors and HIV disease progression or AIDS. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examined 36 articles including 100 psychosocial and disease related relationships. It exhibited a small, but robust positive association between adverse psychosocial factors and HIV progression (correlation coefficient as combined size effect 0.059, 95% confidence interval 0.043-0.074, p<0.001). Notably, sensitivity analyses showed that personality types or coping styles and psychological distress were more strongly associated with greater HIV disease progression than stress stimuli per se, and that all of the immunological and clinical outcome indicators (acquired immunodeficiency syndrome stage, CD4+ T-cell decline, acquired immunodeficiency syndrome diagnosis, acquired immunodeficiency syndrome mortality, and human immunodeficiency virus disease or acquired immunodeficiency syndrome symptoms) except for viral load exhibited detrimental effects by adverse psychosocial factors. In conclusion, the current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.
Full Text Available Malakoplakia is a rare chronic inflammatory disease often confused with neoplasia. In this paper we report two cases of pulmonary Malakoplakia, both with typical clinical diagnosis of tuberculosis and lung cancer. A patient with human T-lymphotropic virus type I (HTLV-1 and diagnosis of adult T-cell leukemia/lymphoma, and another patient with human immunodeficiency virus (HIV, which was treated for tuberculosis, but, after pulmonary lobectomy, was evidenced Rodococosis equi, progressed to death.
Ju, Fang-He; Xu, Ting-Zhen; Hong, Hui-Hua; Mao, He; Wang, Meng; Wang, Zhen
Behcet disease(BD) and Sjogren syndrome(SS) are separate conditions that rarely concomitantly affect an individual. In theory,mild symptoms of patients with BD or SS are easy to igore and,thus,remain undiagnosed. There,it is reasonable to believe there may be some clinical cases of combined diseases that go undiscovered and which needs to be taken seriously. In addition,it has been suggested that herpes simplex virus(HSV) types 1 and 2 are associated with BD,but have not been shown to be correlated to the direct pathogenesis of BD. The role of HSV in BD needs more research and attention. Here,we report a young woman who had both BD and SS. The first symptom of the disease was fever. However,the HSV type 1 IgG and HSV type 2 IgM antibody results were positive in our case and,which rendered this case unique. BD and SS concomitantly affect the individual,and BD was the acute type. IV methylprednisolone was used for 9 days and then oral glucocorticoids was used to instead,and the treatment works very well. BD and SS can concomitantly affect an individual,and we believe that HSV-2 may be directly related to the pathogenesis of BD. The nature of BD as an auto-inflammatory disorder, autoimmune disorder, or both, is controversial. If we can find more patients who combined affected these two disease, it might helpful for us to understand the nature of BD. For patients with clinical diagnosis of BD or SS,we need to be alert that it may combinded the other disease. Long term follow up and detailed inspection are important means to avoid undiscovered.
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... an opportunity for public comment on human immunodeficiency virus (HIV) Patient-Focused Drug...
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug...
Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya
An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease. Copyright © 2014 the American Physiological Society.
Full Text Available AIM: To analyze clinical observation and the efficiency of intravitreal conbercept combined with 532-laser on Coats disease in adulthood. METHODS: This was an retrospective analysis. Six eyes from 6 patients(5 males and 1 femalewith coats disease diagnosed by fundus fluorescein angiography(FFAand optical coherence tomography(OCTwere enrolled. Before the injection, best-corrected visual acuity(BCVAof early treatment of diabetic retinopathy study(ETDRS, non-contact tonometer, ophthalmoscope, fundus photography, FFA, and OCT were examined. The initial average visual acuity(ETDRS letterswere 51.17±15.15. The initial average central retina thickness(CRTwas 303.30±107.87μm. All affected eyes were treated with intravitreal conbercept 0.05mL(10mg/mLcombined with 532-laser. Patients were followed up for 6 to 12mo, with a mean duration of 7.33±1.26mo. Post-treatment BCVA were compared with baseline using repeat analysis. RESULTS: The mean BCVA showed significant improvement during 1 wk, 1, 3mo post-treatment and the latest follow up(PCONCLUSION: Coats disease in adulthood more likely to have lower symptom and have a better response on treatment. Intravitreal conbercept combined with 532-laser significantly improve visual acuity and absorb the subretina fluid.
Stratmann, H.G.; Mark, A.L.; Walter, K.E.; Fletcher, J.W.; Williams, G.A.
To evaluate the presence of coronary artery disease (CAD), atrial pacing and thallium 201 scintigraphy were performed in 36 patients with stable angina pectoris who were unable to perform an adequate exercise stress test. All patients underwent cardiac catheterization. Nine patients had previously undergone coronary artery bypass surgery. Significant CAD (one or more lesions greater than or equal to 50%) was present in 33 patients. Atrial pacing produced ischemic ST segment depression (greater than or equal to 1 mm) in 18 (55%) patients with CAD, and angina in 20 patients (61%). As the number of vessels with CAD increased, there was no significant change in the sensitivities of pacing-induced angina or ST segment depression for detecting CAD. In the 3 patients without CAD, ST segment depression occurred in 1 patient and angina in none. Thallium 201 scintigraphy demonstrated perfusion defects in 27 (82%) patients with CAD, with fixed defects seen in 13 studies (39%) and reversible defects in 15 (45%). In the 3 patients without CAD, no perfusion defects were seen. The thallium 201 scan successfully predicted the presence of CAD in patients with single-vessel disease but usually underestimated the number of vessels involved in patients with multivessel disease. Combined sensitivity of pacing-induced ST segment depression and an abnormal thallium 201 scan finding for detecting CAD was 91%. The authors conclude that combined atrial pacing and thallium 201 scintigraphy is a useful test for detecting CAD in patients unable to perform an adequate exercise stress test
Hosie, Margaret J; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C
Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the 'gold standard' laboratory test for FIV serology. PCR-based assays vary in performance. Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats
... Health Topics Arthritis and Rheumatic Diseases Arthritis and Rheumatic Diseases Arthritis is often used to refer to any ... primary immunodeficiency syndrome March 11, 2013 Arthritis and Rheumatic Disease News Research Brief | January 9, 2017 Tofacitinib Shows ...
Full Text Available Feline immunodeficiency virus (FIV is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV. Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1 inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2 inhibition of fusion of the virus membrane with the cell membrane; (3 blockade of reverse transcription of viral genomic RNA; (4 interruption of nuclear translocation and viral DNA integration into host genomes; (5 prevention of viral transcript processing and nuclear export; and (6 inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.
la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Malvagia, Sabrina; Funghini, Silvia; Moriondo, Maria; Valleriani, Claudia; Lippi, Francesca; Ombrone, Daniela; Della Bona, Maria Luisa; Speckmann, Carsten; Borte, Stephan; Brodszki, Nicholas; Gennery, Andrew R; Weinacht, Katja; Celmeli, Fatih; Pagel, Julia; de Martino, Maurizio; Guerrini, Renzo; Wittkowski, Helmut; Santisteban, Ines; Bali, Pawan; Ikinciogullari, Aydan; Hershfield, Michael; Notarangelo, Luigi D; Resti, Massimo; Azzari, Chiara
Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program. This study evaluate whether mass spectrometry can identify metabolite abnormalities in dried blood spots (DBSs) from affected patients, with the final goal of individuating the disease at birth during routine newborn screening. DBS samples from 9 patients with genetically confirmed PNP-combined immunodeficiency, 10,000 DBS samples from healthy newborns, and 240 DBSs from healthy donors of different age ranges were examined. Inosine, dIno, guanosine, and dGuo were tested by using tandem mass spectrometry (TMS). T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) levels were evaluated by using quantitative RT-PCR only for the 2 patients (patients 8 and 9) whose neonatal DBSs were available. Mean levels of guanosine, inosine, dGuo, and dIno were 4.4, 133.3, 3.6, and 3.8 μmol/L, respectively, in affected patients. No indeterminate or false-positive results were found. In patient 8 TREC levels were borderline and KREC levels were abnormal; in patient 9 TRECs were undetectable, whereas KREC levels were normal. TMS is a valid method for diagnosis of PNP deficiency on DBSs of affected patients at a negligible cost. TMS identifies newborns with PNP deficiency, whereas TREC or KREC measurement alone can fail. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Tokuchi, Ryo; Hishikawa, Nozomi; Matsuzono, Kosuke; Takao, Yoshiki; Wakutani, Yosuke; Sato, Kota; Kono, Syoichiro; Ohta, Yasuyuki; Deguchi, Kentaro; Yamashita, Toru; Abe, Koji
The aim of the present study was to compare the effects of a galantamine only therapy and a combination therapy with galantamine plus ambulatory cognitive rehabilitation for Alzheimer's disease patients. For this retrospective cohort study, we enrolled 86 patients with Alzheimer's disease, dividing them into two groups - a galantamine only group (group G, n = 45) and a combination with galantamine plus ambulatory rehabilitation group (group G + R, n = 41). The present cognitive rehabilitation included a set of physical therapy, occupational therapy and speech therapy for 1-2 h once or twice a week. We compared the Mini-Mental State Examination and Frontal Assessment Battery for cognitive assessment, and Geriatric Depression Scale, Apathy Scale, and Abe's Behavioral and Psychological Symptoms of Dementia score for affective assessment in two groups over 6 months. The baseline Mini-Mental State Examination score was 20.2 and 18.7 in groups G and G + R, respectively. Other baseline data (Frontal Assessment Battery, Geriatric Depression Scale, Apathy Scale, and Abe's Behavioral and Psychological Symptoms of Dementia) were not different between the two groups. Although group G kept all the scores stable until 6 months of the treatment, the Apathy Scale score showed a significant improvement in group G + R as early as 3 months, followed by the Mini-Mental State Examination and Frontal Assessment Battery improvements at 6 months (*P = 0.04 and *P = 0.02, respectively). The Geriatric Depression Scale and Abe's Behavioral and Psychological Symptoms of Dementia did not show any changes. The combination therapy of galantamine plus ambulatory cognitive rehabilitation showed a superior benefit both on cognitive and affective functions than galantamine only therapy in Alzheimer's disease patients. © 2015 Japan Geriatrics Society.
Roshini Sarah Abraham
Full Text Available Common variable immunodeficiency (CVID is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%(Chapel et al., 2008;Cunningham-Rundles, 2008, autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004;Chapel et al., 2008 of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia and neutropenia. While it may seem paradoxical prima facie that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.
Monique E. Francois
Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.
Francois, Monique E; Gillen, Jenna B; Little, Jonathan P
Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.
objective;To search for an effective therapy for trealing motor disorder due to Parkinson's disease(PD).Methods;Fifty cases in a treatrnent group were treated by acupuncture combined with madopar,and 30 cases in a control group treated by madopar only.Results;A total effective rate of 92%was achieved with obvious alleviation of motor disorder in the treatment group,which was significantly higher than that in the control group(P＜0.05).Conclusion;Acupuncture can enhance therapeutic effects of western medicine and lessen the dose of the medicine needed.
Full Text Available Allergen specific immunotherapy (ASIT is a very effective technique in treatment of many allergic diseases. It greatly improves the quality of life. There's a risk of adverse system reactions at the time of ASIT. Treatment with anti Ige antibodies (omalizumab, xolair allows decreasing the circulating Ige level and lessening an expression of high affinity fc_r1 receptors on the surface of basophiles and mast cells, inhibition of early and late phase of allergic inflammatory response. Combination of antibige therapy and ASIT can lead to decrease of risk of adverse system reactions.Key words: omalizumab, anti Ige antibodies, allergen specific immunotherapy.
Campbell, W B; Baird, R N; Cole, S E; Evans, J M; Skidmore, R; Woodcock, J P
A new method is presented for assessing the femorodistal segment in multisegmental arterial disease, using the Laplace transform technique of Doppler waveform analysis. Blood velocity/time waveforms were obtained at femoral and ankle levels in three groups of limbs--50 without arterial disease, 12 with isolated aortoiliac stenoses, and 32 with femoropopliteal occlusions, with and without proximal disease. The waveforms were analysed for Laplace transform and pulsatility index values. The omega 0 coefficients of the Laplace transform analysis at femoral and ankle levels were compared in each subject, as the omega 0 gradient (femoral/ankle omega 0): and pulsatility index damping factor (femoral/ankle P1) was also calculated. The omega 0 gradient was shown to detect femoropopliteal occlusion in the presence of multisegmental arterial disease and to give some indication of its haemodynamic significance. The diagnostic accuracy of the omega 0 gradient was superior to that of pulsatility index damping factor. When combined with its existing ability to detect aortoiliac stenosis, this new application of the Laplace transform method offers the possibility both of a system for complete localisation of significant arterial lesions, and potential for follow-up of vascular surgical procedures in the lower limb, from two simple Doppler recordings.
Ramadan, Wijdan H; Kabbara, Wissam K; El Khoury, Ghada M; Al Assir, Sarah A
Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD. PMID:26586940
Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively
Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik
to hypogammaglobulinaemia, and increased risk of both infections as well as cancer. We employed whole exome sequencing (WES) to identify mutations associated with primary immunodeficiency in severely affected children. We present WES data on 2 patients with severe immunodeficiency. WES was performed using TruSeq exome kit...... and severe infections including sepsis. Second, we identified compound heterozygote stopgain mutations in RAD52 and a heterozygote mutation in LRRC8A in a 7 year-old girl with T-cell deficiency, reduced T-cell mediated B-cell activity, hypogammaglobulinaemia, prolonged splenomegali and benign adenopathy. RAD......52 has not previously been linked to immunodeficiency and we are currently investigating the functional consequences. Knowledge of the mechanisms underlying immunodeficiencies is a prerequisite for understanding disease pathogenesis. WES allows the demonstration of immune defects that may result from...
Park, Myoung Su; Park, Ki Hwan; Bahk, Gyung Jin
Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (Pclimatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate. Copyright © 2017 Elsevier B.V. All rights reserved.
Zou, Honghong; Zhou, Baoqin; Xu, Gaosi
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)
This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The
Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung
This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The
Mansueto Gomes Neto
Full Text Available INTRODUCTION: In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE: To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS: We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT: The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION: Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk
Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S
Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.
Wong, Emily M; Walby, William F; Wilson, Dennis W; Tablin, Fern; Schelegle, Edward S
Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive (SH) Wistar-Kyoto rats. Conscious, mature adult male normal Wistar-Kyoto (NW) and SH rats were exposed to one of the following atmospheres: filtered air (FA); UFPM (∼ 250 μg/m3); O3 (1.0 ppm); or UFPM + O3 (∼ 250 μg/m3 + 1.0 ppm) combined for 6 h, followed by an 8 h FA recovery period. Lung sections were evaluated for lesions in the large airways, terminal bronchiolar/alveolar duct regions, alveolar parenchyma, and vasculature. NW and SH rats were similarly affected by the combined-pollutant exposure, displaying severe injury in both large and small airways. SH rats were particularly susceptible to O3 exposure, exhibiting increased injury scores in terminal bronchioles and epithelial degeneration in large airways. UFPM-exposure groups had minimal histologic changes. The chemical composition of UFPM was altered by the addition of O3, indicating that ozonolysis promoted compound degradation. O3 increased the biologic potency of UFPM, resulting in greater lung injury following exposure. Pathologic manifestations of CVD may confer susceptibility to air pollution by impairing normal lung defenses and responses to exposure.
Rusu, Mirabela; Madabhushi, Anant, E-mail: email@example.com [Case Western Reserve University, Cleveland, Ohio 44106 (United States); Bloch, B. Nicolas; Jaffe, Carl C. [Boston University School of Medicine, Boston, Massachusetts 02118 (United States); Genega, Elizabeth M. [Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215 (United States); Lenkinski, Robert E.; Rofsky, Neil M. [UT Southwestern Medical Center, Dallas, Texas 75235 (United States); Feleppa, Ernest [Riverside Research Institute, New York, New York 10038 (United States)
Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework
Rusu, Mirabela; Madabhushi, Anant; Bloch, B. Nicolas; Jaffe, Carl C.; Genega, Elizabeth M.; Lenkinski, Robert E.; Rofsky, Neil M.; Feleppa, Ernest
Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework
Korkmaz, Fatma Nur; Ozen, Gulsen; Ünal, Ali Uğur; Kahraman Koytak, Pınar; Tuncer, Nese; Direskeneli, Haner
Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although
López Hernández, N; García Escrivá, A; Shalabi Benavent, M
Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
Mookkan, Jeyamurugan; De, Soumita; Shetty, Pranesha; Kulkarni, Nagaraj M; Devisingh, Vijayaraj; Jaji, Mallikarjun S; Lakshmi, Vinitha P; Chaudhary, Shilpee; Kulathingal, Jayanarayan; Rajesh, Navin B; Narayanan, Shridhar
To evaluate the effect of vildagliptin alone and in combination with metformin or rosiglitazone on murine hepatic steatosis in diet-induced nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were fed with high fat diet (60 Kcal %) and fructose (40%) in drinking water for 60 days to induce NAFLD. After the induction period, animals were divided into different groups and treated with vildagliptin (10 mg/kg), metformin (350 mg/kg), rosiglitazone (10 mg/kg), vildagliptin (10 mg/kg) + metformin (350 mg/kg), or vildagliptin (10 mg/kg) + rosiglitazone (10 mg/kg) orally for 28 days. Following parameters were measured: body weight, food intake, plasma glucose, triglyceride (TG), total cholesterol, liver function tests, and liver TG. Liver histopathology was also examined. Oral administration of vildagliptin and rosiglitazone in combination showed a significant reduction in fasting plasma glucose, hepatic steatosis, and liver TGs. While other treatments showed less or no improvement in the measured parameters. These preliminary results demonstrate that administration of vildagliptin in combination with rosiglitazone could be a promising therapeutic strategy for the treatment of NAFLD.
Powers, Karen M; Kay, Denise M; Factor, Stewart A; Zabetian, Cyrus P; Higgins, Donald S; Samii, Ali; Nutt, John G; Griffith, Alida; Leis, Berta; Roberts, John W; Martinez, Erica D; Montimurro, Jennifer S; Checkoway, Harvey; Payami, Haydeh
Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking, coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated. 2007 Movement Disorder Society
Razavi, A R; Taeb, M; Afshari, F; Khavari, S; Abbaspoor, M
Ten wheat lines were studied to determine gene effects and combining ability in some bread wheat genotypes to yellow rust disease. Ten parental lines and F1 were evaluated in a randomized complete block design with three replications in Agricultural and Natural Resources Research Center, Mashhad, Iran. Two races (134E134A+ and 4E0A+) were used for this study. Latent Period (LP) and Infection Type (IT) were measured in the field and greenhouse. Results showed significant differences between races in their pathogenicity and between genotypes in their resistance to the pathogen. Diallel cross carried out between the parents and progenies and thereafter were analyzed by the method of Griffing and Haymans. The General Combining Ability (GCA) and Special Combining Ability (SCA) for all traits were significant and showed additive variance was more important. Test for validity of diallel hypothesis proved epistasis effect for all traits. P1, P2 and F1 showed significant difference between all traits in generations mean analysis. Average degree of dominance ranged from partial to over dominance for resistance or susceptibility. Dominance, additive and epistatic types of gene action were responsible for the genetic control of the traits. However, except for additive-additive component, non-additive effect of genes could not be fixed by self-fertilization.
Bertinchamp, Rémi; Gérard, Laurence; Boutboul, David; Malphettes, Marion; Fieschi, Claire; Oksenhendler, Eric
In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients. The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia. Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia. Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID). The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Smith, Will; McMahon, David; Nymark, Maria
Context • Approximately 25% of the US population suffers from dry eyes or some abnormality of the exposed ocular surface. Investigation of effective modalities for their management is needed. Objective • The study intended to examine the efficacy of a proprietary, daily, Dry Eye Protocol consisting of daily use of a moist, heated, ocular compress and intake of an omega-3 dietary supplement in treatment of ocular surface disease. Design • The research team designed a 4-wk, clinically based, open-label, multicenter cohort study. Setting • The study took place at 6 private eye care practices throughout the United States: Beverly Hills, CA, USA; San Diego, CA, USA; Sunnyvale, CA, USA; Park City, UT, USA; Tarpon Spring, FL, USA; and Kennewick, WA, USA. Participants • Participants were adults between 18 and 75 y of age who had established ocular surface disease based on clinical findings and the results of testing using the ocular surface disease index (OSDI). Intervention • For period of 30 d, participants used a combined daily protocol that included (1) application of a moist, heated, eye compress and (2) a nutritional therapy via an omega-3 supplement in an oral triglyceride form. Outcome Measures • Measures included the OSDI and a test of tear break-up time (TBUT). Results • Of the original 35 participants, 33 completed the 4-wk protocol. The participants using the proprietary Dry Eye Protocol showed significant improvements from baseline, demonstrated by a 49% decrease in OSDI scores (P = .0015); and 46% of participants reported becoming asymptomatic of dry eye symptoms. A significant improvement was also observed in TBUT, increasing from 3.0 to 5.4 s. Conclusions • Daily use of the proprietary Dry Eye Protocol that included a high dosage of triglyceride omega-3 and use of a moist, heated, compress daily showed significant improvement for participants in OSDI and TBUT and should be considered to be a first-line therapy for patients with dry eye
Full Text Available Traditional Chinese medicine (TCM was formed two thousand years ago, and developed in the following centuries. TCM has a unique way of looking at health and illness. Zheng (syndrome is the basic unit and key term in TCM theory. Zheng is the pathological generalization of a certain stage in the development of disease. Treatment based on syndrome differentiation and disease differentiation of TCM is the basic principle to know and treat diseases,and a kind of special method to study diseases in TCM. In Han Dynasty (200 AD, doctor Zhang Zhongjing proposed Liujing Bianzheng (the differential diagnosis in accordance with the theory of six channels to diagnose and treat diseases in Treatise on Febrile and Miscellaneous Diseases. In other words, he divided diseases into six channels diseases based on patient’s Zhengs. Six channels diseases almost include all of the disease according to his classification standards. In addition, there are development rules in the progress of six channels diseases.Therefore, we hypothesized that combination of six channels disease and Zheng on the basic of differentiation of six channels is a new pattern of diagnosis and treatment diseases in TCM, which is beneficial to the understanding of a certain disease and makes disease treatment more convenient, fast and effective.
Full Text Available Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS and a weighted (wGRS approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7 versus 12.09 (SD 1.8, p = 4.577×10(-40. The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57, p = 2.010×10(-65. To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC. The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p = 2.13×10(-8. Additionally, the AUC for HLA-C alone (rs10484554 was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p = 0.18, highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p = 4.91×10(-6 and family history (p = 0.020. Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.
Zhang, Chaoxian; Guo, Like; Guo, Xiaofeng; Guo, Xiaohe; Li, Guangyan
To study the clinical curative effect, safety and mechanism of action of electroacupuncture combined with Zhizhukuanzhong capsules (ZZKZC) in treating gastroesophageal reflux disease (GERD). A total of 480 patients with confirmed GERD were randomly divided into four groups: the electroacupuncture group, the ZZKZC group, the combined therapy group, and the control group, with 120 cases in each group. Each case in the electroacupuncture group was treated with electroacupuncture on Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6),Taichong (LR 3) and Gongsun (SP 4) once daily for 6 weeks. Each case in the ZZKZC group was treated with oral administration of 1.29 g ZZKZC three times daily. The combined therapy group had electroacupuncture and ZZKZC. The control group was given oral administration of 5 mg mosapride three times and 20 mg pantoprazole twice daily. The 24-hour intraesophageal total number of reflux episodes with pH or = 0.14), the number of long-term (> or = 5 min) reflux episodes, the percentage of upright time, the percentage of supine time, the percentage of total time of pH or = 0.14), endoscopic grading score, symptom score, quality of life score, and adverse reactions were observed before treatment, at the end of treatment and 54 weeks after treatment in the four groups. The 24-hour intraesophageal pH and bile reflux, endoscopic grading score and symptom score were all significantly decreased at the end of treatment in every group, while the scores of 8 dimensions of quality of life were all increased compared with those before treatment (Pelectroacupuncture group 54 weeks after treatment compared with the end of treatment (P>0.05); however, these indices all significantly deteriorated in the ZZKZC and control groups (P>0.05). The short and long-term total efficacy rates in the combined therapy group showed significant superiority to those in the other groups (PElectroacupuncture and ZZKZC play an important role in inhibiting intraesophageal acid and
Cohen, W.A.; Maravilla, K.R.; Gerlach, R.; Claypool, K.; Coombs, R.; Collier, A.
This paper presents an evaluation of the progression of neurologic and neuropsy chological dysfunction in human immunodeficiency virus (HIV) positive homosexual men in order to define the natural history of this disease. Markers predictive of disease progression are discussed. Experimental methods and materials are included and results are assessed
E. A. Latysheva
Full Text Available The problems of primary immunodeficiency in Russia and the ways of solving of them are discussed in the article. Primary immunodeficiency is a group of rare diseases, so awareness of this pathology in the medical community and among patients is very low. This leads to late diagnosis and inadequate treatment of patients with such conditions. The result of the late beginning of treatment is early development of disability, and the high mortality rate of patients, as well as the high costs of the treatment of complications of primary immunodeficiency and sick-leave certificates for the government. Today in time and adequate therapy allows patients not only to reach adulthood without signs of disability, and to lead an active way of life, but to have healthy children. Given the high cost of therapy in many countries, the issue of providing patients with life-saving drugs remains unresolved. The global practice is to involve social organizations and funds. One of the foundations supporting educational programs, development of laboratories and research in the field of primary immunodeficiency is the Foundation of the Jeffrey Modell. A network of centres for primary immunodeficiency supported by the Jeffrey Modell Foundation (JMF-centers has started its functioning over the territory of the Russian Federation since 2011 in order to improve diagnostics and treatment of patients with primary immunodeficiency. A brief description of activity of these centers is presented in the article.
Full Text Available Abstract Reverse transcription-polymerase chain reaction (RT-PCR has limited sensitivity when treating complicated samples, such as feces, waste-water in farms, and nucleic acids, protein rich tissue samples, all the factors may interfere with the sensitivity of PCR test or generate false results. In this study, we developed a sensitive RT-PCR, combination of red blood cell adsorption, for detecting Newcastle disease virus (NDV. One pair of primers which was highly homologous to three NDV pathotypes was designed according to the consensus nucleocapsid protein (NP gene sequence. To eliminate the interfere of microbes and toxic substances, we concentrated and purified NDV from varied samples utilizing the ability of NDV binding red blood cells (RBCs. The RT-PCR coupled with red blood cell adsorption was much more sensitive in comparison with regular RT-PCR. The approach could also be used to detect other viruses with the property of hemagglutination, such as influenza viruses.
Nuti, R; Turchetti, V; Righi, G; Vattimo, A
The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.
Masaryk, T.J.; Modic, M.T.; Ross, J.S.; Ruggieri, P.; Laub, G.; Haacke, E.M.
This study tested the accuracy and clinical utility of a three-dimensional MR angiographic technique of the cervical carotids in combination with a routine spin-echo examination of the brain as a screening examination for cerebrovascular disease in 23 patients. The technique used a fast low-angle shot sequence with a reduced echo time and voxel size, gradient refocusing, and time of flight effects to minimize signal loss secondary to phase dispersion and maximize vessel contrast. Subsequent multiplanar three-dimensional reconstructions were obtained at 5 0 increments about the z-axis via ray-tracing linear thresholding algorithms. Examinations were compared with IV/IA-digital subtraction angiography or Doppler US as the objective of accuracy. Results of this ongoing study indicate that an MR angiographic screening examination can be coupled with routine brain MR imaging with only a 10-14 minute extension of examination time, providing both a vascular and a parenchymal evaluation
Lindegaard Pedersen, Brian; Bækgaard, Niels; Quistorff, Bjørn
BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests...... were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function...... group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P
Tokareva, E.A.; Sergienko, V.B.; Sidorenko, B.A.
The paper presents the results from examination of 67 patients with coronary heart disease verified by a bicycle ergometric tests, 48 underwent 201 Tl myocardial scintigraphy along with a dipyridamole test, 19, the scintigraphy in combination with an isoproterenol test. The feasibilities of employing the procedures in the diagnosis of coronary heart disease were compared by statistic analysis
María Eugenia Vargas-Camaño
Full Text Available The secondary immunodeficiency’s, previously presented in immunocompetent individuals. The lack of primary or secondary response to the presence of a foreign antigen, in the case of infections is a sentinel data in the diagnosis of immunodeficiency (can be primary or secondary, in the case of a self antigen may generate the presence of Cancer. Cancer has shown an increase in the prevalence and incidence globally. Most current medical treatments in cancer are focused primarily on immunomodulatory actions (immunosuppression / immune stimulation or both. Knowledge of key concepts from the perspective of innate and acquired immunity lead to cancer development, engaging immune surveillance and escape mechanisms of this that contribute to better understand the origin, behavior and treatment of neoplasm’s. These treatments can cause immunological disorders such as allergy, anaphylaxis, lack of response immunogenicity care fields specialist in Allergy and Clinical Immunology.
Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M
To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M
Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.
Lacher, M.J.; Toner, K.
The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record
Changbo Ou, Ningning Shi1, Qing Pan, Deyu Tian, Wenshu Zeng and Cheng He*
Full Text Available Currently, infectious bursal disease (IBD is a highly contagious disease leading to huge economic losses in poultry industry. Our objective was to investigate potential therapeutic effects of the combined extracts of Rhizoma Dryopteridis crassirhizomatis and Fructus mume (RDCFM against IBDV infection. Seventy-two 4-week-old SPF chickens were randomly divided into six groups and inoculated intranasally with 0.2 ml of 102.5 EID50 of IBDV strain CJ801. Twenty-four hours post infection, the birds were orally administered with 400, 200 and 100 mg/kg BW of RDCFM, respectively, 125 mg/kg Astragalus polysaccharide (ASP and saline water, respectively for 5 days and then monitored daily for 10 days. Finally, the remaining birds were euthanized to collect the sera for detecting antibodies and immune organs for determining the immune organs index as well as virus loads. The herbal extracts improved survival rate and relative body gain rate. Virus loads in bursa of Fabricius in herbal treated groups decreased significantly while higher antibody levels were detected in the three RDCFM groups as compared to those of ASP and infection group. These results implied that chickens administered with 100-200 mg/kg of RDCFM for 5 days could improve protection against IBDV infection and RDCFM may be a promising alternative to ASP and egg yolk antibody.
Csontos, Ágnes Anna; Molnár, Andrea; Piri, Zsolt; Pálfi, Erzsébet; Miheller, Pál
The purpose of malnutrition screening is to predict the probability of a worse outcome due to nutritional factors. The Malnutrition Universal Screening Tool (MUST) can be used for screening in inflammatory bowel disease (IBD); however, it does not provide details about body composition. Our aim was to assess the body composition and combine this with the MUST method to screen risk of malnutrition and sarcopenia. A total of 173 IBD outpatients were enrolled in this cross-sectional study. The MUST scale indicated 21.4% of IBD patients to be at risk of malnutrition. A risk of sarcopenia was detected in 27.7%. However, one third of these patients were not considered to be at risk by their MUST score. Furthermore, Crohn's disease (CD) patients had a strongly unfavorable fat-free mass index (FFMI) value compared to ulcerative colitis (UC) patients, and these differences were significant among men (FFMI: 18.62 ± 2.16 vs 19.85 ± 2.22, p = 0.02, in CD and UC males, respectively). As sarcopenia is a relevant prognostic factor, the MUST method should be expanded to include body composition analysis to detect more IBD patients at risk of malnutrition and sarcopenia in order to start their nutritional therapy immediately.
Kadri, Sameer S; Rhee, Chanu; Fortna, Gregory S; O'Grady, Naomi P
The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H
Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.
Palikova, Miroslava; Navratil, Stanislav; Papezikova, Ivana; Ambroz, Petr; Vesely, Tomas; Pokorova, Dagmar; Mares, Jan; Adamovsky, Ondrej; Navratil, Lukas; Kopp, Radovan
Under environmental conditions, fish can be exposed to multiple stressors including natural toxins and infectious agents at the same time. This study brings new knowledge on the effects of controlled exposure to multiple stressors in fish. The aim of this study was to test the hypothesis that influence of cyanobacterial biomass and an infection agent represented by the white spot disease can combine to enhance the effects on fish. Common carps were divided into four groups, each with 40 specimens for 20 days: control group, cyanobacterial biomass exposed group, Ichthyophthirius multifiliis-infected fish (Ich) and cyanobacterial biomass-exposed fish + Ichthyophthirius multifiliis-infected fish. During the experiment we evaluated the clinical signs, mortality, selected haematological parameters, immune parameters and toxin accumulation. There was no mortality in control fish and cyanobacterial biomass-exposed fish. One specimen died in Ichthyophthirius multifiliis-infected fish and the combined exposure resulted in the death of 13 specimens. The whole leukocyte counts (WBC) of the control group did not show any significant differences. Cyanobacteria alone caused a significant increase of the WBC on day 13 (p≤0.05) and on day 20 (p≤0.01). Also, I. multifiliis caused a significant elevation of WBC (p≤0.01) on day 20. Co-exposition resulted in WBC increased on day 13 and decrease on day 20, but the changes were not significant. It is evident from the differential leukocyte counts that while the increase of WBC in the group exposed to cyanobacteria was caused by elevation of lymphocytes, the increase in the group infected by I. multifiliis was due to the increase of myeloid cells. It well corresponds with the integral of chemiluminescence in the group infected by I. multifiliis, which is significantly elevated on day 20 in comparison with all other groups. We can confirm additive action of different agents on the immune system of fish. While single agents seemed to
Cao, Zhiyong; Zhang, Ping; He, Zhiqing; Yang, Jing; Liang, Chun; Ren, Yusheng; Wu, Zonggui
Current study was designed to investigate the effects of obstructive sleep apnea (OSA) combined dyslipidemia on the prevalence of atherosclerotic cardiovascular diseases (ASCVD). This was a cross-sectional study and subjects with documented dyslipidemia and without previous diagnosis of OSA were enrolled. Polysomnography was applied to evaluate apnea-hypopnea index (AHI). Based on AHI value, subjects were classified into four groups: without OSA, mild, moderate and severe OSA groups. Clinical characteristics and laboratory examination data were recorded. Relationship between AHI event and lipid profiles was analyzed, and logistic regression analysis was used to evaluate the effects of OSA combined dyslipidemia on ASCVD prevalence. Totally 248 subjects with dyslipidemia were enrolled. Compared to the other 3 groups, subjects with severe OSA were older, male predominant and had higher smoking rate. In addition, subjects with severe OSA had higher body mass index, waist-hip ratio, blood pressure, and higher rates of overweight and obesity. Serum levels of fasting plasma glucose, glycated hemoglobin, LDL-C and CRP were all significantly higher. ASCVD prevalence was considerably higher in subjects with severe OSA. AHI event in the severe OSA group was up to 35.4 ± 5.1 events per hour which was significantly higher than the other groups (P dyslipidemia plus no-OSA group (reference group), OSA enhanced ASCVD risk in subjects with dyslipidemia, regardless of OSA severity. After extensively adjusted for confounding variables, the odds of dyslipidemia plus mild-OSA was reduced to insignificance. While the effects of moderate- and severe-OSA on promoting ASCVD risk in subjects with dyslipidemia remained significant, with severe-OSA most prominent (odds ratio: 1.52, 95% confidence interval: 1.13-2.02). OSA combined dyslipidemia conferred additive adverse effects on cardiovascular system, with severe-OSA most prominent.
Vicenzi, Elisa; Liò, Pietro; Poli, Guido
The human immunodeficiency virus type-1 (HIV-1) is the etiological agent of the acquired immunodeficiency syndrome (AIDS), a disease highly lethal in the absence of combination antiretroviral therapy. HIV infects CD4(+) cells of the immune system (T cells, monocyte-macrophages and dendritic cells) via interaction with a universal primary receptor, the CD4 molecule, followed by a mandatory interaction with a second receptor (co-receptor) belonging to the chemokine receptor family. Apart from some rare cases, two chemokine receptors have been evolutionarily selected to accomplish this need for HIV-1: CCR5 and CXCR4. Yet, usage of these two receptors appears to be neither casual nor simply explained by their levels of cell surface expression. While CCR5 use is the universal rule at the start of every infection regardless of the transmission route (blood-related, sexual or mother to child), CXCR4 utilization emerges later in disease coinciding with the immunological deficient phase of infection. Moreover, in most instances CXCR4 use as viral entry co-receptor is associated with maintenance of CCR5 use. Since antiviral agents preventing CCR5 utilization by the virus are already in use, while others targeting either CCR5 or CXCR4 (or both) are under investigation, understanding the biological correlates of this "asymmetrical" utilization of HIV entry co-receptors bears relevance for the clinical choice of which therapeutics should be administered to infected individuals. We will here summarize the basic knowledge and the hypotheses underlying the puzzling and yet unequivocal role of CXCR4 in HIV-1 infection.
H. IJspeert (Hanna); M. Wentink (Marjolein); D. van Zessen (David); G.J.A. Driessen (Gertjan); V.A.S.H. Dalm (Virgil); M.P. van Hagen (Martin); I. Pico-Knijnenburg (Ingrid); E.J. Simons (Erik J.); J.J.M. van Dongen (Jacques); A. Stubbs (Andrew); M. van der Burg (Mirjam)
textabstractThe antigen receptor repertoires of B- and T-cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen
Marchiori, Edson; Melo, Alessandro Severo Alves de; Ossa, Alfonso Jaramillo [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia
In this article are reviewed the principal radiologic manifestations of inflammatory and tumoral diseases the compromise the lungs of patients with acquired immunodeficiency syndrome. In the group of inflammatory diseases the radiologic aspects of pneumocystosis, cytomegalovirus disease, cryptococcosis, tuberculosis and bacterial pneumonias are emphasized. In the neoplasic diseases' group the aspects of lymphoma and Kaposi's sarcoma are specially presented. (author)
Nuno Ribeiro Ferreira
Full Text Available Kaposi's sarcoma (KS is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV. The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8. The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.
Full Text Available Human immunodeficiency virus infection is the first major pandemic of the 20th century. At present, almost 10 million people are known to be infected with this virus, and it is estimated that by the year 2000, approximately 40 million people will be infected. Transmission of this deadly infection is predominantly by sexual contact. Individuals infected with this virus pass through several predictable stages with progressive decrease in circulating CD4+ T cells. During the advanced stage, these patients develop various opportunistic infections or malignancies, or both. It is this advanced stage that was first recognized as AIDS, which has a 100% mortality rate. The opportunistic organisms that can involve the eye in patients with AIDS include cytomegalovirus, herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, Candida, and others. Intraocular lesions from these agents often represent disseminated infections. Visual morbidity occurs secondary to retinitis due to cytomegalovirus, herpes zoster, or Toxoplasma gondii. Anti-viral agents such as ganciclovir or foscarnet are effective against cytomegalovirus infection. The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important. Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations. In the AIDS patient, the ophthalmologist thus has an opportunity to make not only a slight-saving, but also life-saving diagnosis of disseminated opportunistic infections.
Oct 2, 2006 ... This mini-review takes a look at the evaluations of South African medicinal plants to determine ... Key words: Human immunodeficiency virus, Medicinal plants, South Africa. ... The greatest degree of antiviral activity against.
... with antiretroviral therapy (ART). Starting ART early—before symptoms appear—greatly reduces the risk of developing acquired immunodeficiency syndrome (AIDS, the final stage of HIV infection), having AIDS-related complications, or dying of ...
Human immunodeficiency virus (HIV) infection in tuberculosis patients in Addis ... METHODS: A cross-sectional survey whereby blood sample was collected ... of co-infection appeared to have increased compared to previous studies, 6.6%, ...
Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013).
In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is 500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage 55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Full Text Available Primary immunodeficiencies are rare, inborn errors that result in impaired, disordered or uncontrolled immune responses. Whilst symptomatic and prophylactic treatment is available, hematopoietic stem cell transplantation is an option for many diseases, leading to cure of the immunodeficiency and establishing normal physical and psychological health. Newborn screening for some diseases, whilst improving outcomes, is focusing research on safer and less toxic treatment strategies, which result in durable and sustainable immune function without adverse effects. New conditioning regimens have reduced the risk of hematopoietic stem cell transplantation, and new methods of manipulating stem cell sources should guarantee a donor for almost all patients. Whilst incremental enhancements in transplantation technique have gradually improved survival outcomes over time, some of these new applications are likely to radically alter our approach to treating primary immunodeficiencies.
Khanna, Reena; Bressler, Brian; Levesque, Barrett G; Zou, Guangyong; Stitt, Larry W; Greenberg, Gordon R; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J; Donner, Allan; Vandervoort, Margaret K; Morris, Joan C; Feagan, Brian G
Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤ 4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95
Bravo, Àlex; Li, Tong Shu; Su, Andrew I; Good, Benjamin M; Furlong, Laura I
Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects.Database URL: https://zenodo.org/record/29887?ln¼en#.VsL3yDLWR_V. © The Author(s) 2016. Published by Oxford University Press.
Barban, Francesco; Annicchiarico, Roberta; Pantelopoulos, Stelios; Federici, Alessia; Perri, Roberta; Fadda, Lucia; Carlesimo, Giovanni Augusto; Ricci, Claudia; Giuli, Simone; Scalici, Francesco; Turchetta, Chiara Stella; Adriano, Fulvia; Lombardi, Maria Giovanna; Zaccarelli, Chiara; Cirillo, Giulio; Passuti, Simone; Mattarelli, Paolo; Lymperopoulou, Olga; Sakka, Paraskevi; Ntanasi, Eva; Moliner, Reyes; Garcia-Palacios, Azucena; Caltagirone, Carlo
The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants. Copyright © 2015 John Wiley & Sons, Ltd.
Rowland, Nathan C; Starr, Philip A; Larson, Paul S; Ostrem, Jill L; Marks, William J; Lim, Daniel A
Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain. © 2014 International Parkinson and Movement Disorder Society.
Hoshino, Taro; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Mori, Honami; Yoshida, Izumi; Tabei, Kaoru
Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.
Full Text Available Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs have been isolated from primary immunodeficiency (PID patients exposed to oral poliovirus vaccine (OPV. Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2% excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8% were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2. Non-polio enteroviruses were detected in 30 patients (4.7%. Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.
Lakhotia, Manoj; Pahadia, Hans Raj; Kumar, Harish; Singh, Jagdish; Tak, Sandeep
Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon.
Schulak, J.A.; Sharp, W.J.
A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence
Cui, J-J; Peng, B; Lin, W
The aim of this study is to analyze the effects of combining cone beam computed tomography (CBCT) technology with visual root canal recurrence in the treatment of elderly patients with dental pulp disease. 56 cases of elderly patients with dental pulp disease were contiguously selected, and randomly divided into the control group (70 teeth from 27 patients) and the observation group (77 teeth from the rest 29 patients). We adopted CBCT technology combined with conventional root canal therapy in control group and CBCT technology combined with visual root canal recurrence in observation group to compare the clinical effects. It was found that there was no statistical difference in duration of operation between the two groups (p>0.05). The operation times and the VAS during and after operation of the observation group were significantly less than that of the control group (ppulp disease.
Song, Peipei; He, Jiangjiang; Li, Fen; Jin, Chunlin
China is facing the great challenge of treating the world's largest rare disease population, an estimated 16 million patients with rare diseases. One effort offering promise has been a pilot national project that was launched in 2013 and that focused on 20 representative rare diseases. Another government-supported special research program on rare diseases - the "Rare Diseases Clinical Cohort Study" - was launched in December 2016. According to the plan for this research project, the unified National Rare Diseases Registry System of China will be established as of 2020, and a large-scale cohort study will be conducted from 2016 to 2020. The project plans to develop 109 technical standards, to establish and improve 2 national databases of rare diseases - a multi-center clinical database and a biological sample library, and to conduct studies on more than 50,000 registered cases of 50 different rare diseases. More importantly, this study will be combined with the concept of precision medicine. Chinese population-specific basic information on rare diseases, clinical information, and genomic information will be integrated to create a comprehensive predictive model with a follow-up database system and a model to evaluate prognosis. This will provide the evidence for accurate classification, diagnosis, treatment, and estimation of prognosis for rare diseases in China. Numerous challenges including data standardization, protecting patient privacy, big data processing, and interpretation of genetic information still need to be overcome, but research prospects offer great promise.
Miulescu Rucsandra Dănciulescu
Full Text Available Acquired immunodeficiency syndrome (AIDS is a human immune system disease characterized by increased susceptibility to opportunistic infections, certain cancers and neurological disorders. The syndrome is caused by the human immunodeficiency virus (HIV that is transmitted through blood or blood products, sexual contact or contaminated hypodermic needles. Antiretroviral treatment reduces the mortality and the morbidity of HIV infection but is increasingly reported to be associated with increasing reports of metabolic abnormalities. The prevalence and incidence of diabetes mellitus in patients on antiretroviral therapy is high. Recently, a joint panel of American Diabetes Association (ADA and European Association for the Study of Diabetes (EASD experts updated the treatment recommendations for type 2 diabetes (T2DM in a consensus statement which provides guidance to health care providers. The ADA and EASD consensus statement concur that intervention in T2DM should be early, intensive, and uncompromisingly focused on maintaining glycemic levels as close as possible to the nondiabetic range. Intensive glucose management has been shown to reduce microvascular complications of diabetes but no significant benefits on cardiovascular diseases. Patients with diabetes have a high risk for cardiovascular disease and the treatment of diabetes should emphasize reduction of the cardiovascular factors risk. The treatment of diabetes mellitus in AIDS patients often involves polypharmacy, which increases the risk of suboptimal adherence
Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries. Copyright © 2011 Elsevier B.V. All rights reserved.
Full Text Available The article describes a case of combined osteoporosis and osteomalacia in a patient with Parkinson’s disease and vertebral pain syndrome. Osteomalacia caused by deficiency and metabolic disorders of vitamin D leads to osteoid mineralization impairment that greatly limits the possibilities of osteoporosis treatment. The treatment of Parkinson’s disease and osteotropic drugs contributed to decreasing intensity of the pain syndrome.
Sabin, C A; d'Arminio Monforte, A; Friis-Moller, N; Weber, R; El-Sadr, W M; Reiss, P; Kirk, O; Mercie, P; Law, M G; De Wit, S; Pradier, C; Phillips, A N; Lundgren, J D; Schölvinck, Elisabeth H.
BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors
Full Text Available Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1 1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China *These authors contributed equally to this work Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD in hypertensive adults. Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1 rapid decline in renal function and 2 annual rate of eGFR decline. Results: The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57. However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95 was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL levels. More importantly, there was an interaction
Harris, Joshua D; Hussey, Kristen; Wilson, Hillary; Pilz, Kyle; Gupta, Anil K; Gomoll, Andreas; Cole, Brian J
The aim of this study was to analyze patient-reported outcomes in those undergoing the triad of simultaneous osteotomy, meniscal transplantation, and articular cartilage repair. Patients undergoing simultaneous meniscal transplantation, distal femoral or proximal tibial osteotomy, and articular cartilage surgery by a single surgeon (B.J.C.) were analyzed. Meniscal transplantation was performed using bone-in-slot techniques. Distal femoral and high tibial osteotomies were performed for valgus and varus malalignment, respectively. Microfracture, autologous chondrocyte implantation, and osteochondral autograft or allograft were performed for articular cartilage disease. Validated patient-reported and surgeon-measured outcomes were collected. Preoperative and postoperative outcomes and medial versus lateral disease were compared using Student t tests. Eighteen participants (mean age, 34 ± 7.8 years; symptomatic patients, 7.4 ± 5.6 years; 2.4 ± 1.0 surgical procedures before study enrollment; mean follow-up, 6.5 ± 3.2 years) were analyzed. Two thirds of participants had medial compartment pathologic conditions and one third had lateral compartment pathologic processes. At final follow-up, there were statistically significant clinically meaningful improvements in International Knee Documentation Committee (IKDC) subjective classification, Lysholm score, and 4 Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores. Postoperative 12-item short form (SF-12) physical and mental component scores were not significantly different from preoperative scores. The Kellgren-Lawrence classification grade was 1.5 ± 1.1 at 2.5 ± 3.0 years after surgery. There was a significantly higher preoperative SF-12 physical composite score (PCS) in participants with lateral compartment pathologic conditions (v medial compartment conditions) (P = .011). Although there were 13 reoperations in 10 patients (55.5% reoperation rate), only one patient was converted to knee arthroplasty (5
Full Text Available The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS epidemic is of unprecedented gravity and is spreading rapidly, notably in the most disadvantaged regions of the world. The search for a preventive vaccine is thus an absolute priority. For over 10 years the French National Agency for AIDS research (ANRS has been committed to an original program combining basic science and clinical research. The HIV preventive vaccine research program run by the ANRS covers upstream research for the definition of immunogens, animal models, and clinical research to evaluate candidate vaccines. Most researchers in 2004 believe that it should be possible to obtain partial vaccine protection through the induction of a strong and multiepitopic cellular response. Since 1992, the ANRS has set up 15 phases I and II clinical trials in order to evaluate the safety and the capacity of the candidate vaccines for inducing cellular immune responses. The tested candidate vaccines were increasingly complex recombinant canarypox viruses (Alvac containing sequences coding for certain viral proteins, utilized alone or combined with other immunogens (whole or truncated envelope proteins. ANRS has also been developing an original strategy based on the utilization of lipopeptides. These comprise synthetic fragments of viral proteins associated with lipids that facilitate the induction of a cellular immune response. These approaches promptly allowed the assessment of a prime-boost strategy combining a viral vector and lipopeptides.
Bajic, Vladimir B.; Essack, Magbubah
The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer's Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent
Full Text Available Common variable immunodeficiency (CVID has only scarcely been associated with ocular symptoms and rarely with retinal disease. In this case we describe a patient with distinct morphological and functional alterations in the retina. The patient presents with characteristic changes in retinal pigment epithelium, autofluorescence, and electrophysiology.
Verhagen, L.M.; Warris, A.; Soolingen, D. van; Groot, R. de; Hermans, P.W.M.
The burden of childhood tuberculosis (TB) is influenced by the human immunodeficiency virus (HIV) epidemic and this dangerous synergy affects various aspects of both diseases; from pathogenesis and the epidemiologic profile to clinical presentation, diagnosis, treatment, and prevention. HIV-infected
Full Text Available The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.
Jiang, Hanqiang; Ni, Wei; Xu, Bin; Lei, Yu; Tian, Yanlong; Xu, Feng; Gu, Yuxiang; Mao, Ying
The outcome of patients with hemorrhagic moyamoya disease (MMD) after cerebral revascularization is uncertain. The purpose of this study was to delineate the efficacy of this surgical method in the treatment of hemorrhagic MMD. Between January 2007 and August 2011, a consecutive cohort of 113 patients with hemorrhagic MMD was enrolled into this prospective single-center cohort study. The surgical method was combined direct and indirect bypass. The cumulative probability of the primary end point (all stroke and deaths from surgery through 30 days after surgery and ipsilateral recurrent hemorrhage afterward) was analyzed. The angiographic outcome was measured by the following parameters: bypass patency, reduction of basal MMD vessels, improved degree of dilation, and branch extension of the anterior choroidal and posterior communicating arteries (AChA-PCoA). Of the 113 enrolled cases, CT scans revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases (31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was extremely dilated with extensive branches beyond the choroidal fissure. A total of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5 patients, 4 of whom died of the rebleeding event. The cumulative probability of the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105 unoperated hemispheres (35.2%). Revascularization may provide a benefit over conservative therapy for hemorrhagic MMD patients. The improvement of dilation and branch extension of AChA-PCoA might be correlated with the low rebleeding rate.
Shamir, Reuben R; Dolber, Trygve; Noecker, Angela M; Walter, Benjamin L; McIntyre, Cameron C
Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naïve Bayes, and random forest. Measures of medication dosages, time factors, and symptom-specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P < 0.05) and their effect on outcomes was of similar magnitude to that of DBS. Using those results, the combined machine learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. Copyright © 2015 Elsevier Inc. All rights reserved.
Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen
The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.
Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set
Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun; Lee, Jae Hong; Roh, Jee Hoon
To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease
Full Text Available Warfarin is used as anticoagulant and Compound Danshen prescription (CDP is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs with atrial fibrillation (AF. Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP on the pharmacokinetics (PK and pharmacodynamics (PD profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment. The population PK (PPK and PPK-PD models were established to assess patient demographics, genetic polymorphisms and CDDP as covariates. And the Seattle Angina Questionnaire was used to evaluate clinical efficacy, and the bleeding risk of combination was analyzed. The results indicated that CDDP had little influence on PK and PD profiles of warfarin in most patients and the combination of CCDP and warfarin would be a promising alternative regime for CHD with AF patients. The study was registered on China Clinical Trial Registry with number ChiCTR-ONRC-13003523.
Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto
Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient's symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients.
Ospanov, Oral B.; Orekeshova, Akzhunis M.; Fursov, Roman A.; Yelemesov, Aset A.
Obesity and gastroesophageal reflux disease (GERD) are serious medical, social, and economic problems of modern society. A pilot randomized two-arm controlled clinical study was conducted to compare laparoscopic plication of the greater gastric curvature combined with Nissen fundoplication (LFN+LGP) versus only Nissen fundoplication (LFN). The…
Behrens, Frank; Meier, Lothar; Prinz, Jörg C; Jobst, Jürgen; Lippe, Ralph; Löschmann, Peter-Andreas; Lorenz, Hanns-Martin
To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.
Full Text Available Invasive fungal infections usually affect patients with immunodeficiencies and very rarely patients with no known or identifiable risk factors. Diagnosis could be delayed in patients without previously known immunodeficiencies due to a low index of suspicion, leading to a delay in treatment and a potential poor outcome. We report a case of a postpartum woman with no history of immuno-compromised disease who developed left hemiparesis with evidence of invasive aspergollosis affecting the nervous system, and leading to fatal outcome. The patient had a mass-like lesion in the neuroimaging with soft tissue shadowing in the chest x-ray leading to initial diagnosis of tuberculosis. The brain biopsy showed changes consistent with a diagnosis of aspergillosis. The source of the aspergillus infection was not clear. Aspergillus infection should be considered in patients with no identifiable immunodeficiencies who have abnormal brain imaging and chest x-ray, as early treatment may alter the outcome.
Emily M. Mace
Full Text Available Human natural killer (NK cells play a critical role in the control of viral infections and malignancy. Their importance in human health and disease is illustrated by severe viral infections in patients with primary immunodeficiencies that affect NK cell function and/or development. The recent identification of patients with phosphoinositide-3-kinase (PI3K-signaling pathway mutations that can cause primary immunodeficiency provides valuable insight into the role that PI3K signaling plays in human NK cell maturation and lytic function. There is a rich literature that demonstrates a requirement for PI3K in multiple key aspects of NK cell biology, including development/maturation, homing, priming, and function. Here, I briefly review these previous studies and place them in context with recent findings from the study of primary immunodeficiency patients, particularly those with hyperactivating mutations in PI3Kδ signaling.
Researches on the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine are becoming a hot spot in andrology, but many recent studies of this kind have failed to explain the connotation of integrated traditional Chinese and Western medicine in andrology. Related existing problems include repeated researches into the same indexes of action mechanisms of different therapeutic principles of traditional Chinese medicine (TCM), Chinese herbal compound and special prescriptions, studies focusing on individual diseases but ignoring symptoms, immature syndrome models for studies of mechanisms, and too much attention to uncertain or immature target mechanisms. The stress should be placed on the action mechanisms of Chinese herbal compound and special prescriptions on male diseases and, what is more important, on the clarification of the essential principles of differentiation and treatment of TCM syndromes. In the recent years, proteomics, genomics, transcriptomics and metabolomics have shed some light upon researches into the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine in andrology. An insight into the TCM syndrome, a macroscopic inductive analysis, and a comprehension of such microcosmic aspects as the gene, protein, metabolism and metagenome may contribute to some breakthroughs and new ideas in the studies of disease-syndrome combination in integrated traditional Chinese and Western medicine in andrology.
Amato, Dominick; Patterson, Mary Anne
Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy
Funda Erol Çipe
Full Text Available Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1 was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.
Barbiero, Sandra Mari; D?Azevedo Sica, Caroline; Schuh, Daniela Schneid; Cesa, Claudia Ciceri; de Oliveira Petkowicz, Rosemary; Pellanda, Lucia Campos
Background Children who have unhealthy lifestyles are predisposed to develop hypertension, dyslipidemia and other complications. The epidemic of obesity is also affecting children with congenital heart disease. The aim of this study is to estimate the prevalence of obesity and describe associated risk factors, including family history in children with congenital heart disease. Methods A cross-sectional study with 316 children and adolescents with congenital heart disease seen in an outpatient...
Cole, Donald C; Govender , Nelesh P.; Chakrabarti, Arunaloke; Sacarlal , Jahit; Denning, David
More than 1·6 million people are estimated to die of fungal diseases each year, and about a billion people have cutaneous fungal infections. Fungal disease diagnosis requires a high level of clinical suspicion and specialised laboratory testing, in addition to culture, histopathology, and imaging expertise. Physicians with varied specialist training might see patients with fungal disease, yet it might remain unrecognised. Antifungal treatment is more complex than treatment for bacterial or mo...
Full Text Available During the last two decades, 15 different genes have been reported to be responsible for the monogenic form of Parkinson’s disease (PD, representing a worldwide frequency of 5–10%. Among them, 10 genes have been associated with autosomal recessive PD, with PRKN and PINK1 being the most frequent. In a cohort of 145 unrelated Moroccan PD patients enrolled since 2013, 19 patients were born from a consanguineous marriage, of which 15 were isolated cases and 4 familial. One patient was homozygous for the common LRRK2 G2019S mutation and the 18 others who did not carry this mutation were screened for exon rearrangements in the PRKN gene using Affymetrix Cytoscan HD microarray. Two patients were determined homozygous for PRKN exon-deletions, while another patient presented with compound heterozygous inheritance (3/18, 17%. Two other patients showed a region of homozygosity covering the 1p36.12 locus and were sequenced for the candidate PINK1 gene, which revealed two homozygous point mutations: the known Q456X mutation in exon 7 and a novel L539F variation in exon 8. The 13 remaining patients were subjected to next-generation sequencing (NGS that targeted a panel of 22 PD-causing genes and overlapping phenotypes. NGS data showed that two unrelated consanguineous patients with juvenile-onset PD (12 and 13 years carried the same homozygous stop mutation W258X in the ATP13A2 gene, possibly resulting from a founder effect; and one patient with late onset (76 years carried a novel heterozygous frameshift mutation in SYNJ1. Clinical analysis showed that patients with the ATP13A2 mutation developed juvenile-onset PD with a severe phenotype, whereas patients having either PRKN or PINK1 mutations displayed early-onset PD with a relatively mild phenotype. By identifying pathogenic mutations in 45% (8/18 of our consanguineous Moroccan PD series, we demonstrate that the combination of chromosomal microarray analysis and NGS is a powerful approach to
Shepard, Donald S; Zeng, Wu; Amico, Peter; Rwiyereka, Angelique K; Avila-Figueroa, Carlos
Because human inmmunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) receives more donor funding globally than that for all other diseases combined, some critics allege this support undermines general health care. This empirical study evaluates the impact of HIV/AIDS funding on the primary health care system in Rwanda. Using a quasi-experimental design, we randomly selected 25 rural health centers (HCs) that started comprehensive HIV/AIDS services from 2002 through 2006 as the intervention group. Matched HCs with no HIV/AIDS services formed the control group. The analysis compared growth in inputs and services between intervention and control HCs with a difference-in-difference analysis in a random-effects model. Intervention HCs performed better than control HCs in most services (seven of nine), although only one of these improvements (Bacille Calmette-Guérin vaccination) reached or approached statistical significance. In conclusion, this six-year controlled study found no adverse effects of the expansion of HIV/AIDS services on non-HIV services among rural health centers in Rwanda.
Full Text Available Chagas disease is a zoonotic parasitic disease well-documented throughout the Americas and transmitted primarily by triatomine 'kissing bug' vectors. In acknowledgment of the successful history of vector control programs based on community participation across Latin America, we used a citizen science approach to gain novel insight into the geographic distribution, seasonal activity, and Trypanosoma cruzi infection prevalence of kissing bugs in Texas while empowering the public with information about Chagas disease.We accepted submissions of kissing bugs encountered by the public in Texas and other states from 2013-2014 while providing educational literature about Chagas disease. In the laboratory, kissing bugs were identified to species, dissected, and tested for T. cruzi infection. A total of 1,980 triatomines were submitted to the program comprised of at least seven species, of which T. gerstaeckeri and T. sanguisuga were the most abundant (85.7% of submissions. Triatomines were most commonly collected from dog kennels and outdoor patios; Overall, 10.5% of triatomines were collected from inside the home. Triatomines were submitted from across Texas, including many counties which were not previously known to harbor kissing bugs. Kissing bugs were captured primarily throughout April-October, and peak activity occurred in June-July. Emails to our dedicated account regarding kissing bugs were more frequent in the summer months (June-August than the rest of the year. We detected T. cruzi in 63.3% of tested bugs.Citizen science is an efficient approach for generating data on the distribution, phenology, and infection prevalence of kissing bugs-vectors of the Chagas disease parasite-while educating the public and medical community.
... gene is also involved in the activation of helper T cells (CD4+ T cells). These cells direct ... genetic testing? How can I find a genetics professional in my area? Other Names for This Condition ...
Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng
To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, pclosure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, ppatent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications.
Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew
We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1 rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.
Ayrapetova, N.S.; Tkachenko, A.F.
An attempt was made to optimize the therapy of chronic nonspecific pulmonary diseases using a combination of decimeter range waves (DRW) and broncholytic electroaerosols. The electroaerosols penetrate rapidly deep into the lungs up to the aveoli, combining the action of an electric charge with the pharmaceutical effect. In all, 232 patients were studied (94.8% with chronic bronchitis, 5.2% with chronic pneumonia) manifesting an active inflammatory process, disturbance of the immune status and diminished glucocorticoid activity. After 15 procedures of combined therapy, 88.5% of the patients showed improvement in their clinical status; 65.4% of the control group (receiving only the electroaerosol) also showed improvement. In this combined therapy, the antiinflammatory and immunosuppressive effect were achieved due to the action of DRW; the electroaerosols had a positive effect on the function state of the cardiorespiratory system. 11 references.
Wijburg, F. A.; Rosenblatt, D. S.; Vos, G. D.; Oorthuys, J. W.; van't Hek, L. G.; Poorthuis, B. J.; Sanders, M. K.; Schutgens, R. B.
Metabolic studies are described in a patient who presented at 3 weeks of age with severe anaemia, hyperbilirubinaemia and hypotonicity. Clinically, glycogen storage disease type II (Pompe disease) was suspected because of a massively enlarged heart and hepatosplenomegaly. This was confirmed
Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen
The emergence of network medicine has provided great insight into the identification of disease-related molecules, which could help with the development of personalized medicine. However, the state-of-the-art methods could neither simultaneously consider target information and the known miRNA-disease associations nor effectively explore novel gene-disease associations as a by-product during the process of inferring disease-related miRNAs. Computational methods incorporating multiple sources of information offer more opportunities to infer disease-related molecules, including miRNAs and genes in heterogeneous networks at a system level. In this study, we developed a novel algorithm, named inference of Disease-related MiRNAs based on Heterogeneous Manifold (DMHM), to accurately and efficiently identify miRNA-disease associations by integrating multi-omics data. Graph-based regularization was utilized to obtain a smooth function on the data manifold, which constitutes the main principle of DMHM. The novelty of this framework lies in the relatedness between diseases and miRNAs, which are measured via heterogeneous manifolds on heterogeneous networks integrating target information. To demonstrate the effectiveness of DMHM, we conducted comprehensive experiments based on HMDD datasets and compared DMHM with six state-of-the-art methods. Experimental results indicated that DMHM significantly outperformed the other six methods under fivefold cross validation and de novo prediction tests. Case studies have further confirmed the practical usefulness of DMHM. Copyright © 2018 Elsevier Inc. All rights reserved.
Tijn M. Schouten
Full Text Available Magnetic resonance imaging (MRI is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD, and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N=77 from the prospective registry on dementia study and controls (N=173 from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC of 0.760 (full correlations between functional networks to 0.909 (grey matter density. When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.
Albarillo, Fritzie; O'Keefe, Paul
Infections of the central nervous system (CNS) in individuals with human immunodeficiency virus (HIV) remain a substantial cause of morbidity and mortality despite the introduction of highly active antiretroviral therapy (HAART) especially in the resource-limited regions of the world. Diagnosis of these infections may be challenging because findings on cerebrospinal fluid (CSF) analysis and brain imaging are nonspecific. While brain biopsy provides a definitive diagnosis, it is an invasive procedure associated with a relatively low mortality rate, thus less invasive modalities have been studied in recent years. Diagnosis, therefore, can be established based on a combination of a compatible clinical syndrome, radiologic and CSF findings, and understanding of the role of HIV in these infections. The most common CNS opportunistic infections are AIDS-defining conditions; thus, treatment of these infections in combination with HAART has greatly improved survival.
Full Text Available Genome-wide association studies (GWASs identify single nucleotide polymorphisms (SNPs that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.
Soboleva, L A; Shul'dyakov, A A; Bulkina, N V
In order to study the clinical-pathogenetic efficacy of using cycloferon liniment in the combined therapy of patients with gingivitis on the background of chronic infectious diseases (HIV infection, hepatitis C, brucellosis), medical examination and treatment of 42 patients with this diagnosis has been carried out. It is established, that the use of cycloferon liniment in the combined therapy decreases the infection load in periodontal recess and manifestation of local inflammation, normalizes the immunity indices, and reduces the level of endogenous intoxication. All these factors provide acceleration of the recuperation processes and decrease the frequency of recidivating.
Post, M.J.D.; Berger, J.R.; Quencer, R.M.
As part of a prospective longitudinal study of individuals who are human immunodeficiency virus (HIV) positive, cranial MR imaging was performed on 89 HIV-seropositive patients and correlated with clinical data. MR results were asymptomatics: MR images normal-58, abnormal-16; myelopathics: normal-seven, abnormal-four; encephalopathics: normal-three, abnormal-two. In asymptomatics, neurologic examination was positive in all with positive MR results but positive in only some with negative MR results. The authors concluded that MR imaging can show indirect evidence of HIV infection early in the disease, but abnormalities will be minor and seen only in the minority (21%) of symptomatics; these minor abnormalities may antedate clinical symptoms but not signs; an increase in severity of clinical disease correlates with increasingly severe atrophy and demyelination; and in some seropositives, whether asymptomatic or symptomatic, MR results remain normal
Lepilin, A V; Erokina, N L; Rogatina, T V; Khlusov, I Iu
The objective of this study was to compare results of dynamic magnetotherapy (DMT), transdermal electroneurostimulation (TDENS), and traditional ultrahigh frequency (UHF) therapy in 473 patients with mandibular fractures and concomitant inflammatory diseases of paradontium. The parameters measured in the study included hygienic and paradontal indices, microcirculation patterns (using laser Doppler flowmetry), and the degree of mandibular fragment consolidation. It was shown that combined treatment with DMT and TDENS using an AMO-ATOS-E apparatus permits to eliminate clinical symptoms of paradontal inflammatory diseases twice as fast as traditional ultrahigh frequency therapy and ensures a two-fold reduction in the frequency of complications.
Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi
Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...
Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.
The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...
This study sought to determine the seroprevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg) among blood donors at Bolga-tanga Regional Hospital, Ghana by blood group type, sex and age and also determining the asso-ciation, if any, in the occurrence of the ...
Background: This study assessed the seroprevalence of Helicobacter pylori antibodies among Iranian patients with human immunodeficiency virus (HIV) infection. It also examines whether anti H. pylori seroprevalence was associated with the severity of the HIV infection or the antiretroviral treatment. Material and Methods: ...
Martín-Mateos, María Anunciación; Piquer Gibert, Mónica
In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.
A seroprevalence study of Human immunodeficiency virus (HIV) infection in new patients attending the eye clinic of LAUTECH Teaching Hospital in Osogbo, Osun State, Nigeria showed that twenty-nine patients 2.7%) were positive to HIV1. No patient was positive to HIV 2. There were 21 males (72.4%) and 8 females ...
Objective: To determine the level of awareness, knowledge and practice of human immunodeficiency virus post exposure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnairebased survey conducted among paediatrcians that attended the Paediatric ...
Nov 23, 2015 ... Abstract: Objective: To deter- mine the level of awareness, knowledge and practice of human immunodeficiency virus post ex- posure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnaire- based survey conducted among paediatrcians that ...
Human immunodeficiency virus (HIV) infection and the pharmacological treatment thereof have both been shown to affect mitochondrial function in a number of tissues, and each may cause specific organ pathology through specific mitochondrial pathways. HIV has been shown to kill various tissue cells by activation of ...
Background: There are diverse reports on the prevalence and severity of chronic periodontitis in human immunodeficiency virus (HIV) positive persons. Few studies have been carried out in developing countries in Sub.Saharan Africa. This study was aimed at comparing the prevalence and severity of chronic periodontitis of ...
A 63-year old man was admitted to our Hospital with urethral catheter in situ and having failed medical therapy, he opted for transurethral prostatectomy (TURP) which was done without any post-operative complication. He was known to be afflicted with human immunodeficiency virus and on treatment for 3 years. He also ...
Background: The rehabilitative dental care is important for maintaining adequate nutrition, guarding against wasting syndrome and malnutrition among human immunodeficiency virus (HIV)‑infected individuals. Aim: The aim of this study is to determine the Nigerian dental technology students' knowledge and ...
Kotler, Donald P
The aim of this article is to review the basic biology of infection with HIV-1 and the development of the acquired immunodeficiency syndrome. The discussion will include epidemiology, general description of the retroviruses, pathogenesis of the immune deficiency, clinical consequences, treatment, and treatment outcomes. Aspects of the infection that affect protein and energy balance will be identified.
Full Text Available Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome is a rare monogenic primary immunodeficiency (PID due to mutations of FOXP3, a key transcription factor for naturally occurring (n regulatory T (Treg cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type 1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia, can develop in patients who survive the initial acute phase.The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is haematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease.This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.
Chen, Ruey; Chan, Pi-Tuan; Chu, Hsin; Lin, Yu-Cih; Chang, Pi-Chen; Chen, Chien-Yu; Chou, Kuei-Ru
This is the first meta-analysis to compare the treatment effects and safety of administering donepezil alone versus a combination of memantine and donepezil to treat patients with moderate to severe Alzheimer Disease, particularly regarding cognitive functions, behavioral and psychological symptoms in dementia (BPSD), and global functions. PubMed, Medline, Embase, PsycINFO, and Cochrane databases were used to search for English and non-English articles for inclusion in the meta-analysis to evaluate the effect size and incidence of adverse drug reactions of different treatments. Compared with patients who received donepezil alone, those who received donepezil in combination with memantine exhibited limited improvements in cognitive functions (g = 0.378, p Alzheimer Disease.
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
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.
Mahroum, Naim; Bragazzi, Nicola Luigi; Brigo, Francesco; Waknin, Roy; Sharif, Kassem; Mahagna, Hussein; Amital, Howard; Watad, Abdulla
Human immunodeficiency virus vaccination and pre-exposure prophylaxis represent two different emerging preventive tools. Google Trends was used to assess the public interest toward these tools in terms of digital activities. Worldwide web searches concerning the human immunodeficiency virus vaccine represented 0.34 percent, 0.03 percent, and 46.97 percent of human immunodeficiency virus, acquired immune deficiency syndrome, and human immunodeficiency virus/acquired immune deficiency syndrome treatment-related Google Trends queries, respectively. Concerning temporal trends, digital activities were shown to increase from 0 percent as of 1 January 2004 percent to 46 percent as of 8 October 2017 with two spikes observed in May and July 2012, coinciding with the US Food and Drug Administration approval. Bursts in search number and volume were recorded as human immunodeficiency virus vaccine trials emerged. This search topic has decreased in the past decade in parallel to the increase in Truvada-related topics. Concentrated searches were noticed among African countries with high human immunodeficiency virus/acquired immune deficiency syndrome prevalence. Stakeholders should take advantage of public interest especially in preventive medicine in high disease burden countries.
Rong, Weining; Chen, Xuejuan; Li, Huiping; Liu, Yani; Sheng, Xunlun
To detect the disease-causing genes of 10 retinitis pigmentosa pedigrees by using exon combined target region capture sequencing chip. Pedigree investigation study. From October 2010 to December 2013, 10 RP pedigrees were recruited for this study in Ningxia Eye Hospital. All the patients and family members received complete ophthalmic examinations. DNA was abstracted from patients, family members and controls. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Polymerase chain reaction (PCR) and direct sequencing were used to confirm the disease-causing mutations. Seventy patients and 23 normal family members were recruited from 10 pedigrees. Among 10 RP pedigrees, 1 was autosomal dominant pedigrees and 9 were autosomal recessive pedigrees. 7 mutations related to 5 genes of 5 pedigrees were detected. A frameshift mutation on BBS7 gene was detected in No.2 pedigree, the patients of this pedigree combined with central obesity, polydactyly and mental handicap. No.2 pedigree was diagnosed as Bardet-Biedl syndrome finally. A missense mutation was detected in No.7 and No.10 pedigrees respectively. Because the patients suffered deafness meanwhile, the final diagnosis was Usher syndrome. A missense mutation on C3 gene related to age-related macular degeneration was also detected in No. 7 pedigrees. A nonsense mutation and a missense mutation on CRB1 gene were detected in No. 1 pedigree and a splicesite mutation on PROM1 gene was detected in No. 5 pedigree. Retinitis pigmentosa is a kind of genetic eye disease with diversity clinical phenotypes. Rapid and effective genetic diagnosis technology combined with clinical characteristics analysis is helpful to improve the level of clinical diagnosis of RP.
Asproni, Pietro; Abramo, Francesca; Millanta, Francesca; Lorenzi, Davide; Poli, Alessandro
Tissues from 34 naturally feline immunodeficiency virus (FIV)-infected cats, 13 asymptomatic cats and 21 cats with signs of feline acquired immunodeficiency syndrome (F-AIDS), and 35 FIV-seronegative subjects were examined to determine the presence of amyloid deposits. Twenty experimentally FIV-infected cats and five specific pathogen-free (SPF) control cats were also included in the study. Paraffin-embedded sections from kidney and other organs were submitted to histological and histochemical analysis. Amyloid deposits were identified by a modified Congo red stain and confirmed by electron microscopy to demonstrate the presence of amyloid fibrils in amyloid positive glomeruli. In all positive cases, secondary amyloidosis was identified with potassium permanganate pretreatment and amyloid type was further characterised by immunohistochemistry using primary antibodies against human AA and feline AL amyloids. Amyloid deposits were present in different tissues of 12/34 (35%) naturally FIV-infected cats (seven presenting F-AIDS and five in asymptomatic phase) and in 1/30 FIV-seronegative cats. All the experimentally FIV-infected and SPF subjects showed no amyloid deposits. Amyloidosis has been reported in human lentiviral infections, and the data reported here demonstrate the need, in naturally FIV-infected cats, to consider the presence of amyloidosis in differential diagnosis of hepatic and renal disorders to better assess the prognosis of the disease.
Full Text Available Background: Common variable immunodeficiency (CVID is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment. Methods: Clinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively. Results: The median age at onset was 11-year-old (range 4-51 years. The median age at diagnosis was 14.5-year-old (range 5-66 years. The average time of delay in diagnosis was 5.3 years (range 1-41 years. The most common main complaint was fever due to infections (35 cases, 87.5%. Pneumonia (28 cases, 70% was the most common type of infections. Bronchiectasis was present in 6 patients (15%. Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3− /CD19 + B-cells were 1%-3.14%. Conclusions: Infection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended.
Full Text Available The frequency of acute respiratory infections remains high in childhood. It is impossible to identify etiology most accurately in each particular case. However, according to multiple studies, viruses, their associations with each other and bacteria prevail as causative agents. In addition, it is quite often that a respiratory infection, especially in minor children, is combined with a condition of the gastrointestinal tract. Apart from symptomatic and antiviral therapies in these cases, as the authors of this article demonstrated, it is advisable to use enterosorbents. This tactics results in a decreased level of intoxication, lower intensity and duration of diarrheal syndrome, i.e. more speedy recovery.Key words: acute respiratory infections, condition of gastro tract, intoxication, diarrheal syndrome, treatment, enterosorbents, children. (Pediatric Pharmacology. – 2010; 7(3:88-90
Full Text Available The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN and combined subthalamic nucleus and substantia nigra (STN+SNr high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: 61.3±7.3 years; disease duration: 12.3±5.4 years; Hoehn and Yahr stage: 2.2±0.39 were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS, Modified Fatigue Impact Scale (MFIS, Becks Depression Inventory (BDI-I, Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS, and Parkinson’s Disease Questionnaire (PDQ-39. Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.
Full Text Available Objective: To analyze the effect of atorvastatin combined with Tongxinluo on hemorheology and inflammatory factors in patients with coronary heart disease. Methods: A total of 42 patients with coronary heart disease treated in our hospital between December 2012 and December 2015 were selected and randomly divided into observation group and control group (n=21, control group received routine therapy, observation group received routine therapy + atorvastatin combined with Tongxinluo therapy, and then cardiac function, blood viscosity as well as serum lipid metabolism indexes and inflammation indexes were compared between the two groups after treatment. Results: After 3 courses of treatment, EF value and E/A ratio of observation group were significantly higher than those of control group, and whole blood high shear viscosity, whole blood low shear viscosity and plasma viscosity were significantly lower than those of control group; serum TC, TG, LDL-C, Leptin, Resistin, Visfatin, IL-18, TNF-C, sTREM-1 and MMP-9 levels of observation group after treatment were significantly lower than those of control group, and IL-4, IL-10, IL-37 and MFG-E8 levels were significantly higher than those of control group. Conclusion: Atorvastatin combined with Tongxinluo can optimize the state of coronary heart disease, and it plays a positive role in optimizing hemorheology, inflammation and other aspects.
Full Text Available Objective: To explore the effect of combined application of trimetazidine and metoprolol on plasma BNP in coronary heart disease patients with heart failure and the clinical efficacy. Methods: A total of 140 cases of coronary heart disease patients with heart failure treated in Cardiology Department of our hospital from May 2012 to January 2015 were selected and divided into study group and control group by random number table method. The control group received digitalis, diuretics, ACEI (angiotensin-converting enzyme inhibitor and other conventional drugs for treatment, the study group received combined use of trimetazidine and metoprolol on the basis of routine treatment of the control group, and treatment duration was 12 weeks. Then plasma BNP, systolic blood pressure, heart rate, left ventricular end diastolic diameter (LVEDD, left ventricular end systolic end (LVESD and left ventricular ejection fraction (LVEF of two groups before and after treatment were statistically analyzed, and the overall effect was evaluated. Results: Before treatment, there were no significant differences in plasma BNP, blood pressure, heart rate, LVEDD, LVESD and LVEF between the two groups; after treatment, plasma BNP, blood pressure, heart rate, LVEDD and LVESD of both groups decreased and LVEF increased, but the changes in study group were better than those in control group. Conclusion: Trimetazidine combined with metoprolol has better application effect in plasma BNP decrease and heart function improvement in coronary heart disease patients with heart failure.
Langlais, David; Fodil, Nassima; Gros, Philippe
Genome technologies have defined a complex genetic architecture in major infectious, inflammatory, and autoimmune disorders. High density marker arrays and Immunochips have powered genome-wide association studies (GWAS) that have mapped nearly 450 genetic risk loci in 22 major inflammatory diseases, including a core of common genes that play a central role in pathological inflammation. Whole-exome and whole-genome sequencing have identified more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe inflammatory bowel disease. Combined analysis of inflammatory disease GWAS and primary immunodeficiencies point to shared proteins and pathways that are required for immune cell development and protection against infections and are also associated with pathological inflammation. Finally, sequencing of chromatin immunoprecipitates containing specific transcription factors, with parallel RNA sequencing, has charted epigenetic regulation of gene expression by proinflammatory transcription factors in immune cells, providing complementary information to characterize morbid genes at infectious and inflammatory disease loci.
Barbiero, Sandra Mari; D'Azevedo Sica, Caroline; Schuh, Daniela Schneid; Cesa, Claudia Ciceri; de Oliveira Petkowicz, Rosemary; Pellanda, Lucia Campos
Children who have unhealthy lifestyles are predisposed to develop hypertension, dyslipidemia and other complications. The epidemic of obesity is also affecting children with congenital heart disease. The aim of this study is to estimate the prevalence of obesity and describe associated risk factors, including family history in children with congenital heart disease. A cross-sectional study with 316 children and adolescents with congenital heart disease seen in an outpatient clinic of a reference hospital. Collected sociodemographic data included family history of chronic disease, dietary habits, laboratory tests (total cholesterol, HDL and LDL/cholesterol, triglycerides, fasting glucose, CRP, hematocrit and hemoglobin), and anthropometric assessment. Anthropometric data of the caregivers was self-reported. The prevalence of excess weight was 26.9%. Altered levels of total cholesterol were observed in 46.9%, of HDL in 32.7%, LDL in 23.6% and of triglycerides levels in 20.0%. A higher frequency of family history of obesity (42.6%; p = 0.001), dyslipidemia (48.1%; p = heart disease, it is particularly important to promote a healthy lifestyle in this group.
Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel
There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131
Full Text Available Purpose: To report a case of Coats’ disease managed with the dexamethasone intravitreal implant Ozurdex® (Allergan, Inc., Irvine, Calif., USA combined with retinal photocoagulation. Methods: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats’ disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. Results: The patient’s visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. Conclusions: Ozurdex may be an effective initial therapeutic approach for Coats’ disease with immediate anatomical response and visual improvement.
de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903
Pallavee, P; Samal, Sunita; Samal, Rupal
The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.
Heegaard, Peter M. H.; Stockmarr, Anders; Piñeiro, Matilde
The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect...... gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative...
Full Text Available About 5-10% of patients with myasthenia gravis concomitantly have other autoimmune diseases. However, the coexistence of myasthenia gravis and pernicious anemia is rare. Here, we report a 73-year-old Taiwanese woman who developed myasthenia gravis 5 months after the onset of pernicious anemia. Her myasthenic and pernicious anemia symptoms markedly improved after pyridostigmine, prednisolone and hydroxo-cobalamine treatment. It is important to recognize concurrence of myasthenia gravis and pernicious anemia in the same patient because the therapeutic results for both diseases are rewarding.
The Agricultural Research Service, United States Department of Agriculture and the University of California, Davis, announce the release of three F2:4 breeding populations of iceberg lettuce (Lactuca sativa L.). The breeding populations combine the cor and Verticillium resistance 1 (Vr1) loci to co...
Basant Kumar Bhuyan
Conclusions: The surgical treatment of LCPD with the best expected outcome is still a challenge. Advanced containment methods by one-stage combined osteotomy can be considered as an alternative treatment where femoral head subluxation or deformity which makes containment difficult or impossible by more conventional methods.
Smith, Kara M; Eyal, Eli; Weintraub, Daniel
Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2 mg/d) or placebo. We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on
Frimodt-Møller, Marie; Høj Nielsen, Arne; Strandgaard, Svend
BACKGROUND: Dual blockade of the renin-angiotensin system (RAS) has been claimed to have a specific renal protective effect in chronic kidney disease (CKD). The present short-term study reports on the feasibility of dual blockade in a consecutive group of patients with CKD stage 3-5. METHODS: Forty...
Full Text Available This paper describes the evolution of the pathogenic concepts associated with the infection by the human immunodeficiency virus (HIV, with emphasis to the pathology of the nervous system. Although the first description of damage to the nervous system in the acquired immunodeficiency syndrome (AIDS only appeared in 1982, the dramatic diffusion of the epidemic worldwide, as well as the invariably rapidly fatal outcome of the disease before the introduction of efficient treatment, generated from the beginning an enormous amount of research and re-thinking on a number of pathogenetic concepts. Less than 25 years after the first autopsy series on AIDS patients were published and the virus responsible for AIDS was identified, satisfactory definition and classification of a number of neuropathological complications of HIV infection have been established. This has led to the establishment of accurate clinical and biological diagnosis of the main neurological complications of the disease, which remain a major cause of disability and death in patients. Clinical and experimental studies have provided essential insight into the pathogenesis of CNS lesions and the natural history of the disorder. The relatively recent introduction of effective antiretroviral therapy in 1995-6 dramatically improved the course of prognosis of HIV disease. However, there remain a number of unsolved pathogenetic issues, the most puzzling of which remains the precise mechanism of neuronal damage underlying the specific HIV-related cognitive disorder (HIV-dementia. In addition, although antiretroviral therapy has changed the course of neurological complications, new issues have emerged, such as the lack of improvement or even paradoxical deterioration of the neurological status in treated patients. Interpretation of these complications remains largely speculative, partly because of the small number of neuropathological studies related to the beneficial consequence of this
Komiyama, Kota; Ashikaga, Takashi; Inagaki, Dai; Miyabe, Tomonori; Arai, Marina; Yoshida, Kiyotaka; Miyazawa, Satoshi; Nakada, Akihiro; Kawamura, Iwanari; Masuda, Shinichiro; Nagamine, Sho; Hojo, Rintaro; Aoyama, Yuya; Tsuchiyama, Takaaki; Fukamizu, Seiji; Shibui, Takashi; Sakurada, Harumizu
Sodium bicarbonate and ascorbic acid have been proposed to prevent contrast-induced nephropathy (CIN). The present study evaluated the effect of their combined use on CIN incidence.Methods and Results:We prospectively enrolled 429 patients with chronic kidney disease (CKD: baseline estimated glomerular filtration rate <60 mL/min/1.73 m 2 ) prior to elective coronary catheterization. CIN was defined as absolute (≥0.5 mg/dL) or relative (≥25%) increase in serum creatinine within 72 h. In the saline hydration (n=218) and combined sodium bicarbonate+ascorbic acid (n=211) groups, a total of 1,500-2,500 mL 0.9% saline was given before and after the procedure. In addition, the combination group received 20 mEq sodium bicarbonate and 3 g ascorbic acid i.v. before the procedure, followed by 2 g ascorbic acid after the procedure and a further 2 g after 12 h. There were no significant differences between the basic characteristics and contrast volume in the 2 groups. CIN occurred in 19 patients (8.7%) in the saline group, and in 6 patients (2.8%) in the combined treatment group (P=0.008). Combined sodium bicarbonate and ascorbic acid could prevent CIN following catheterization in CKD patients.
Full Text Available The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.
Full Text Available Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.
Wang, Hui; Ding, Wenyuan
Kummell disease is a clinical syndrome characterized by minor spinal trauma with a symptom-free period from months to years, followed by progressive painful kyphosis. Many surgical options for Kummell disease have been reported in the previous literature; however, no study has mentioned the surgical strategy for patients whose fractured vertebrae were severely compressed and only a slice of superior and inferior end plate was left. Here we report the case of a 69-year-old woman who suffered persistent severe back pain since she slipped and fell 1 year before medical consult. The patient presented with constrained body posture and pressure pain on the thoracolumbar region. Visual analog scale pain under weight bearing was 90/100, and her Oswestry Disability Index score was 74%. Kummell disease was diagnosed on the basis of clinical presentation, trauma history, radiograph, computed tomography, and magnetic resonance imaging. We performed the posterior vertebral column resection through the unilateral osteotomy approach for the patient, and the clinical outcome and radiologic restoration were recorded. One year after the surgery, outpatient follow-up review revealed that the visual analog scale reduced to 10/100 and Oswestry Disability Index reduced to 13%. The posteroanterior and lateral radiograph in the standing position showed bony fusion was achieved at the osteotomy site. No pseudarthrosis or instrumentation-related failure occurred. Posterior vertebral column resection through unilateral osteotomy approach is an effective method for patients with Kummell disease, especially when the fractured vertebrae compressed severely and only a slice of superior and inferior end plate was left. Copyright © 2017 Elsevier Inc. All rights reserved.
Narin, Burcu; Ajaj, Waleed; Goehde, Susanne; Lauenstein, Thomas C.; Langhorst, Jost; Gerken, Guido; Akgoez, Haldun; Ruehm, Stefan G.
MRI of the small bowel is a new method for the assessment of inflammatory bowel diseases. However, inflammatory bowel disease can affect both the small and large bowel. Therefore, our goal was to assess the feasibility of displaying the small bowel and colon simultaneously by MR imaging. Eighteen patients with inflammatory bowel disease were studied. For small bowel distension, patients ingested a solution containing mannitol and locust bean gum. Furthermore, the colon was rectally filled with water. MR examinations were performed on a 1.5-T system. Before and after intravenous gadolinium administration, a T1w data set was collected. All patients underwent conventional colonoscopy as a standard of reference. The oral ingestion and the rectal application of water allowed an assessment of the small bowel and colon in all patients. By means of MRI (endoscopy), 19 (13) inflamed bowel segments in the colon and terminal ileum were detected. Furthermore, eight additional inflammatory lesions in the jejunum and proximal ileum that had not been endoscopically accessible were found by MRI. The simultaneous display of the small and large bowel by MRI is feasible. Major advantages of the proposed MR concept are related to its non-invasive character as well as to the potential to visualize parts of the small bowel that cannot be reached by endoscopy. (orig.)
Steel, John; Burmakina, Svetlana V; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E; Palese, Peter
The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI) and Newcastle disease virus (NDV) can be achieved through vaccination, as part of a broader disease control strategy. We have previously generated a recombinant influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203-8). Here we show this virus is attenuated in primary normal human bronchial epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from lethal challenge with an H5 HA-containing influenza virus through immunisation with the recombinant virus. In addition, in-ovo vaccination of 18-day-old embryonated chicken eggs provided 90% and 80% protection against highly stringent lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus has potential as a safe in-ovo live, attenuated, bivalent avian influenza and Newcastle disease virus vaccine.
Dadparvar, S.; Woods, K.; Magno, R.M.; Sabatino, J. C.; Patil, S.; Dou, Y.
The clinical management of pulmonary embolism and deep venous thrombosis of the legs are similar and require prolonged anticoagulation therapy. The standard diagnostic approach in patients suspected of pulmonary embolism is ventilation-perfusion (V/Q) lung scan and compression ultrasonography to detect deep venous thrombosis. This retrospective study analyzed the role of V Q lung scan and compression ultrasonography in detection of thromboembolic disease. One hundred-twenty consecutive patients (65 female, 55 male) age range 18-95 (mean age 60.7) suspected for pulmonary embolism underwent concomitant V/Q lung scan and compression ultrasonography of the lower extremities. The clinical and radiographic correlation was performed. Of patients with non-diagnostic (low or intermediate probability ) lung scans, 15.4 % (14/91) received anticoagulation therapy for pulmonary embolism. This patients had either high pre-clinical suspicion for PE or underwent pulmonary arterio gram. However, there was an additional 7 % (7/91) increase in the number of patients who received anticoagulation therapy based on the results of ultrasound with confidence interval (3 %-16 %). We conclude that V/Q lung scan is a more sensitive examination for thromboembolic disease, and has a high negative predictive value. Ultrasonography of lower extremities demonstrated higher specificity and positive value. Among patients with non-diagnostic lung scan, the detection rate of thromboembolic disease is improved with addition of ultrasound
Koutouridou, Emmanouela; Planck, Tereza; Uddman, Erik; Lantz, Mikael
Subacute thyroiditis is a common inflammatory disorder of the thyroid gland, possibly of viral etiology, that typically presents with neck pain, fever and tenderness on palpation of the thyroid gland. Graves' disease is an autoimmune thyroid disorder caused by stimulation of the thyroid gland by thyrotropin receptor antibodies (TRAb). The development of Graves´ disease and subacute thyroiditis simultaneously is an uncommon condition and only a few cases have been reported. In this article we present a case of a 46-year old woman diagnosed with Graves´ disease who was started on thiamazole and weeks later developed high fever. Several differential diagnoses were considered such as infection, lymphoma and vasculitis due to thiamazole. Finally, the fine needle aspiration of the thyroid gland displayed histopathological features of subacute thyroiditis. Remarkably, our patient did not have neck pain or tenderness on palpation of the thyroid gland and overall the clinical presentation of subacute thyroiditis was atypical. Thus, subacute thyroiditis may be considered as a potential cause of fever of unknown origin.
Full Text Available Background: The role of obesity in clinical curse of rheumatoid arthritis (RA is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. Materials and Methods: Active RA patients with the disease activity score using 28 joint counts (DAS28 > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week plus hydroxychloroquine (200 to 400 mg/day and prednisolone (2.5 to 10 mg/day and were followed by DAS28 for up to 24 weeks. Results: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001 after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = -0.415, P = 0.005 and waist circumference (r = -0.296, P = 0.05 were correlated with baseline DAS28. Although BMI (r = -0.337, P = 0.025 and waist circumference (r = -0.315, P = 0.038 were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. Conclusion: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients.
Petritsch, B; Köstler, H; Weng, A M; Horn, M; Gassenmaier, T; Kunz, A S; Weidemann, F; Wanner, C; Bley, T A; Beer, M
Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1 H magnetic resonance spectroscopy (MRS) at 3 Tesla. Myocardial lipid content was quantified in vivo by 1 H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1 H-MRS with cardiac cine imaging and LGE MRI in a single examination. Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1 H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1 H-MRS; T 1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.
Tamanai-Shacoori, Zohreh; Chandad, Fatiha; Rébillard, Amélie; Cillard, Josiane; Bonnaure-Mallet, Martine
The purpose of this study was to evaluate various biological effects of silver-zeolite and a polyphenol-rich extract of A. nodosum (ASCOP) to prevent and/or treat biofilm-related oral diseases. Porphyromonas gingivalis and Streptococcus gordonii contribute to the biofilm formation associated with chronic periodontitis. In this study, we evaluated in vitro antibacterial and anti-biofilm effects of silver-zeolite (Ag-zeolite) combined to ASCOP on P. gingivalis and S. gordonii growth and biofilm formation capacity. We also studied the anti-inflammatory and antioxidant capacities of ASCOP in cell culture models. While Ag-zeolite combined with ASCOP was ineffective against the growth of S. gordonii, it showed a strong bactericidal effect on P. gingivalis growth. Ag-zeolite combined with ASCOP was able to completely inhibit S. gordonii monospecies biofilm formation as well as to reduce the formation of a bi-species S. gordonii/P. gingivalis biofilm. ASCOP alone was ineffective towards the growth and/or biofilm formation of S. gordonii and P. gingivalis while it significantly reduced the secretion of inflammatory cytokines (TNFα and IL-6) by LPS-stimulated human like-macrophages. It also exhibited antioxidant properties and decreased LPS induced lipid peroxidation in gingival epithelial cells. These findings support promising use of these products in future preventive or therapeutic strategies against periodontal diseases. PMID:25272151
Rashid, M. H.; Hossain, M. Ashraf; Kashem, M. A.; Kumar, Shiv; Rafii, M. Y.; Latif, M. A.
Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L.) and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur) in Bangladesh for three years (2008, 2009, and 2010). Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%)], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%), and Protaf 250EC, propiconazole (0.05%)], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%); Secure 600 WG, phenomadone + mancozeb (0.2%); and Companion, mancozeb 63% + carbendazim 12% (0.2%)]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale) and the highest increase (38%) of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance. PMID:24723819
Full Text Available The purpose of this study was to evaluate various biological effects of silver-zeolite and a polyphenol-rich extract of A. nodosum (ASCOP to prevent and/or treat biofilm-related oral diseases. Porphyromonas gingivalis and Streptococcus gordonii contribute to the biofilm formation associated with chronic periodontitis. In this study, we evaluated in vitro antibacterial and anti-biofilm effects of silver-zeolite (Ag-zeolite combined to ASCOP on P. gingivalis and S. gordonii growth and biofilm formation capacity. We also studied the anti-inflammatory and antioxidant capacities of ASCOP in cell culture models. While Ag-zeolite combined with ASCOP was ineffective against the growth of S. gordonii, it showed a strong bactericidal effect on P. gingivalis growth. Ag-zeolite combined with ASCOP was able to completely inhibit S. gordonii monospecies biofilm formation as well as to reduce the formation of a bi-species S. gordonii/P. gingivalis biofilm. ASCOP alone was ineffective towards the growth and/or biofilm formation of S. gordonii and P. gingivalis while it significantly reduced the secretion of inflammatory cytokines (TNFα and IL-6 by LPS-stimulated human like-macrophages. It also exhibited antioxidant properties and decreased LPS induced lipid peroxidation in gingival epithelial cells. These findings support promising use of these products in future preventive or therapeutic strategies against periodontal diseases.
M. H. Rashid
Full Text Available Botrytis gray mold (BGM caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L. and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur in Bangladesh for three years (2008, 2009, and 2010. Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%, and Protaf 250EC, propiconazole (0.05%], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%; Secure 600 WG, phenomadone + mancozeb (0.2%; and Companion, mancozeb 63% + carbendazim 12% (0.2%]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale and the highest increase (38% of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.
William F. Griffith
Full Text Available The objective of this report is to describe an urban county hospital human immunodeficiency virus (HIV infection prevention protocol offering prophylactic combination antiretroviral medications to female victims of sexual assault. A retrospective chart review was conducted from June, 2007 through June, 2008 of 151 women who were prescribed antiretroviral prophylaxis by protocol. All women receiving HIV prophylaxis initially screened HIV seronegative. Of the 58 women who reported taking any HIV prophylaxis, 36 (62% were HIV screened at 12 and/or 24 weeks and none had HIV seroconverted. Although the initiation of an HIV post exposure prophylaxis protocol for sexual assault in a county hospital population is feasible, patient follow-up for counseling and HIV serostatus evaluation is an identified barrier
Boujaoude, Ziad; Arya, Rohan; Rafferty, William; Dammert, Pedro
Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders. Pulmonary manifestations are characterised by recurrent rhinosinusitis, respiratory tract infections and bronchiectasis. Less commonly the lung may be affected by lymphoid disorders and sarcoid-like granulomas. Organising pneumonia (OP) is a rare pulmonary manifestation. We report the case of a 32-year-old woman with CVID who presented with fever, dyspnoea and persistent lung infiltrates despite antibiotic therapy. CT of the chest showed bilateral patchy alveolar infiltrates. Pulmonary function tests revealed moderate restriction and reduction in diffusion capacity. Initial bronchoscopy with transbronchial biopsies did not yield a diagnosis but surgical lung biopsies identified OP. Significant clinical, radiographic and physiological improvement was achieved after institution of corticosteroid therapy.
Laviopierre, A.M.; Lawler, G.A.
Toxoplasmosis now constitutes a relatively frequent central nervous system (CNS) complication of AIDS, primary CNS lymphoma being far less common. CT scanning using the double-dose delayed (D-D-D) scan technique has proved an effective way of helping in the diagnosis of these complications. 16 patients with CNS complications of the acquired immunodeficiency syndrome (AIDS) are described. All patients were male homosexuals. The most common demonstrable lesion in the parenchyma was toxoplasmosis, which produced an area of focal oedema, usually containing a central zone of nodular or ring-shaped enhancement. Cerebral atrophy was also a common finding. One patient had diffuse peri-ventricular lymphomatous infiltration, and a further two patients had both cerebral toxoplasmosis and lymphoma. A delayed double dose contrast examination appears to be the most accurate method of outlining the total extent of CNS disease in these patients. 11 refs., 7 figs., 2 tabs