Immunodeficiency disorders

MedlinePlus

... that affect T cells may cause repeated Candida (yeast) infections. Inherited combined immunodeficiency affects both T cells ... infections (including some forms of pneumonia or repeated yeast infections) Symptoms depend on the disorder. For example, ...

Partial central diabetes insipidus in patient with common variable immunodeficiency

PubMed Central

Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto

2012-01-01

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. PMID:22761233

Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry

PubMed Central

Guffey, Danielle; Minard, Charles G.; Orange, Jordan S.

2017-01-01

Introduction Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6–7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors. Methods We analyzed 2537 PID patients registered in USIDNET to determine responses to the field “fatigue” in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs). Results Fatigue was reported in 25.9%(95% CI 23.7–28.3) of PAD patients, compared to 6.4% (95% CI 4.9–8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p < 0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients. Conclusion Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered. PMID:28124237

A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

ERIC Educational Resources Information Center

Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

2007-01-01

Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

Systematic review of vestibular disorders related to human immunodeficiency virus and acquired immunodeficiency syndrome.

PubMed

Heinze, B; Swanepoel, D W; Hofmeyr, L M

2011-09-01

Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear. To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome. Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched. We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study. We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life.

Clinical correlates of HIV-associated neurocognitive disorders in South Africa.

PubMed

Joska, John A; Fincham, Dylan S; Stein, Dan J; Paul, Robert H; Seedat, Soraya

2010-04-01

Human immunodeficiency virus-associated neurocognitive disorders (HAND) occurs globally and across different genetic clades of the virus. However, few studies have examined HAND in South Africa, despite the prevalence of HIV in this region of the world, and the predominance of clade C. The present study examined the relationship between a number of demographic and clinical variables in a sample of 536 patients attending HIV clinics in South Africa. HAND was present in 23.5% of the sample and was associated with older age, a low educational level among those with post-traumatic stress disorder (PTSD) and alcohol abuse among those with many months since diagnosis. These results suggest that HAND is common among patients in South Africa, and is associated with clinical variables such as PTSD and alcohol abuse. This underlines the impact of HIV on the nervous system and the importance of screening for co morbid mental health conditions.

Primary antibody deficiencies at Queen Rania Children Hospital in Jordan: single center experience.

PubMed

Habahbeh, Zeyad M; Abu-Shukair, Mohammad E; Almutereen, Mohammad A; Alzyoud, Raed M; Wahadneh, Adel M

2014-03-01

Primary antibody deficiency, the most common primary immunodeficiency disorder, represents a heterogeneous spectrum of conditions caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. This retrospective study aimed at description and analysis of demographic, clinical, immunological features and complications of subjects diagnosed with primary antibody deficiency at a referral center in Jordan. The medical records of pediatric patients who were diagnosed as primary antibody deficiency (PAD) during the period from January 2006 to June 2013 were reviewed. Patients were diagnosed as PADs based on the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiency (ESID) diagnostic criteria. A total number of 53 patients with PAD were identified; 37(70%) males and 16(30%) females, 16(30%) patients with congenital agammaglobulinemia, 16(30%) patients with common variable immunodeficiency, 4(7.5%) patients with IgG subclass deficiency, 10(19%) cases with transient hypogammaglobulinemia of infancy and 7(13.5%) patients as undefined PAD. The most common infection among patients was pneumonia (62%); followed by suppurative otitis media in 49% of patients. Cytopenia was the most noted autoimmune association and was found at prevalence of 22 %, other autoimmune associations (17%) including inflammatory arthritis, discoid lupus, inflammatory bowel disease, vasculitis and celiac disease. The prevalence of long-term complications was 58%, the most frequent ones were; stunted growth in 13%, bronchiectasis and lymphoproliferation in 11% for each. Our results indicated that congenital agammaglobulinemia and common variable immunodeficiency are the most frequent primary antibody deficiency in our patients. The awareness of families, general population as well as primary health physicians is crucial in the establishment of early diagnosis and prompt commencement of appropriate therapy for PADs.

Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency

PubMed Central

AGARWAL, SHRADHA; MAYER, LLOYD

2013-01-01

Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency. PMID:23501398

Infectious complications of the primary immunodeficiencies.

PubMed

Stiehm, E R; Chin, T W; Haas, A; Peerless, A G

1986-07-01

The primary manifestation of the immunodeficiencies is undue susceptibility to infection. This means too many, too severe, too prolonged, too complicated and too unusual infections. Infections in immunodeficiency have a characteristic cause depending on the nature of the immune deficiency. Antibody deficiencies are associated with infections with gram-positive infections. Cellular immune deficiencies are associated with mycobacterial, protozoan, fungus, virus, and opportunistic bacterial infection. Phagocytic disorders are associated with staphylococcal, fungal, and gram-negative organisms. Complement disorders are associated by neisserial infections. Infections have also been implicated in the pathogenesis of some immunodeficiencies in some circumstances. These include human T lymphotropic virus type III (HTLV-III), rubella virus, cytomegalovirus, and Epstein-Barr virus. Several infectious syndromes in specific immunodeficiencies have been identified. Examples include enteric cytopathic human orphan (ECHO) virus encephalitis in agammaglobulinemia, and meningococcal meningitis in C6 deficiency. Infections can also be induced by live vaccines given in immunodeficiency (e.g., paralytic polio in agammaglobulinemia.) Unusual infectious syndromes will be illustrated including parainfluenza infection in severe combined and immunodeficiency, Legionella pneumonia in chronic granulomatous disease, and Cryptosporidium infection in hyper-IgM immunodeficiency.

Concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine: a dimorphic presentation of iatrogenic immunodeficiency-associated lymphoproliferative disorder with evidence suggestive of multiclonal transformability of B cells by Epstein-Barr virus.

PubMed

Foo, Wen-Chi; Huang, Qin; Sebastian, Siby; Hutchinson, Charles B; Burchette, Jim; Wang, Endi

2010-12-01

A small fraction of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma develop Epstein-Barr virus-positive B-cell lymphoproliferative disorders. These Epstein-Barr virus-B-cell lymphoproliferative disorders are thought to be related to immune suppression induced by fludarabine/other chemotherapeutic regimens. As in other immunodeficiency-associated lymphoproliferative disorders, these disorders demonstrate a heterogeneous histological spectrum that ranges from polymorphic to monomorphic to classical Hodgkin lymphoma-like lesions. We report a case of concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine. Both classical Hodgkin lymphoma and plasmablastic lymphoma were positive for Epstein-Barr virus-encoded RNA, whereas classical Hodgkin lymphoma was also positive for Epstein-Barr virus- latent membrane protein 1, suggesting a different viral latency. Immunoglobulin gene rearrangement studies demonstrated distinct clones in the plasmablastic lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. These findings suggest biclonal secondary lymphomas associated with iatrogenic immunodeficiency. Epstein-Barr virus-B-cell lymphoproliferative disorders in the setting of chronic lymphocytic leukemia/small lymphocytic lymphoma, in particular those arising after chemotherapy, should be separated from true Richter's transformation, and be categorized as (iatrogenic) immunodeficiency-associated lymphoproliferative disorder. Copyright © 2010 Elsevier Inc. All rights reserved.

Common variable immunodeficiency: experience in Puerto Rico.

PubMed

Santaella, María L; Font, Ivonne; Disdier, Orville

2005-03-01

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by hypogammaglobulinemia and an increased susceptibility to infections. The degree and the type of deficiency of serum immunoglobulins, as well as, the clinical course vary from patient to patient, hence the term "variable". The aim of this report is to describe the clinical characteristics and the response to gammaglobulin therapy of a group of patients with CVI followed at the University Hospital of the Puerto Rico Medical Center. To our knowledge, no data on primary immunodeficiencies in Puerto Rico has been reported in the literature. The study group exhibits specific characteristics as compared to other reported series.

Oral and dental health status in patients with primary antibody deficiencies.

PubMed

Meighani, Ghasem; Aghamohammadi, Asghar; Javanbakht, Honarmand; Abolhassani, Hassan; Nikayin, Sina; Jafari, Seyed Mehryar; Ghandehari Motlagh, Mehdi; Shamshiri, Ahmad Reza; Rezaei, Nima

2011-12-01

Primary antibody deficiencies (PAD) are a group of immune system disorders, associated with decreased levels of secretory and protective immunoglobulins. Because of the important role of immunoglobulins in the protection of oral cavity, patients with PADs are more susceptible to dental caries or oral manifestations. This study was performed to investigate the oral and dental manifestations of PADs patients. In this study, 33 patients with PADs (21 common variable immunodeficiency, 8 X-linked agammaglobulinemia and 4 hyper IgM syndrome) and 66 controls were examined; the number of decayed, missed and filled teeth (DMFT) were investigated. Aphthous was the most frequent manifestation in PADs patients (38.7%), which was significantly 16.7% higher than the controls (p=0.03). The patients with PADs showed significantly higher presentation of other oral and dental manifestations, including herpes sores, candidiasis tonsillitis, gingivitis, calculus, enamel hypoplasia and other ulcerations. The mean DMFT scores were 6.15±3.6 and 1.93±0.4 in PADs patients and controls, respectively (p<0.001). Although the patients with common variable immunodeficiency had higher means of DMFT in comparison with other groups of PADs, this difference was not statistically significant. This study showed significantly higher frequency of oral and dental manifestations in the patients with PADs compared to controls. Therefore, regular examination of oral cavity could be suggested in this group of immunodeficient patients.

Management of common variable immunodeficiency by subcutaneous IgG self-administration during pregnancy - a case report.

PubMed

Marasco, Carolina; Venturelli, Alberta; Rao, Luigia; Vacca, Angelo; Carratù, Maria Rosaria

2017-08-01

Patients with common variable immunodeficiency are prone to infections, and this poses a particular challenge during pregnancy, when the requirement for immunoglobulin (Ig) replacement therapy is even more demanding so as to achieve an effective protection also of the fetus. This case report highlights the benefits observed with subcutaneous IgG self-administration in the management of common variable immunodeficiency (CVID) during pregnancy, in terms of efficacy and safety.

Skin signs of primary immunodeficiencies: how to find the genes to check.

PubMed

Ettinger, M; Schreml, J; Wirsching, K; Berneburg, M; Schreml, S

2018-02-01

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.

Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.

PubMed

Albuquerque, Andreia

2014-11-16

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.

Primary Immunodeficiency Diseases in Highly Consanguineous Populations from Middle East and North Africa: Epidemiology, Diagnosis, and Care

PubMed Central

Al-Mousa, Hamoud; Al-Saud, Bandar

2017-01-01

Middle East and North Africa region (MENA)1 populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance. Studies of PIDs in the region had contributed into the discovery and the understanding of several novel immunodeficiency disorders. Few MENA countries have established national registries that helped in estimating the prevalence and defining common PID phenotypes. Available reports from those registries suggest a predominance of combined immunodeficiency disorders in comparison to antibody deficiencies seen in other populations. Access to a comprehensive clinical immunology management services is limited in most MENA countries. Few countries had established advanced clinical immunology service, capable to provide extensive genetic testing and stem cell transplantation for various immunodeficiency disorders. Newborn screening for PIDs is an essential need in this population considering the high incidence of illness and can be implemented and incorporated into existing newborn screening programs in some MENA countries. Increased awareness, subspecialty training in clinical immunology, and establishing collaborating research centers are necessary to improve patient care. In this review, we highlight some of the available epidemiological data, challenges in establishing diagnosis, and available therapy for PID patients in the region. PMID:28694805

Cystic fibrosis, common variable immunodeficiency and Aspergers syndrome: an immunological and behavioural challenge.

PubMed

Chotirmall, S H; Low, T B; Hassan, T; Branagan, P; Kernekamp, C; Flynn, M G; Gunaratnam, C; McElvaney, N G

2011-06-01

Cystic fibrosis (CF) is of particular importance in Ireland as the Irish population has both the highest incidence (2.98/10,000) and the highest carrier rate (1 in 19) in the world. Primary immunodeficiency has not been previously reported as co-existing with CF. We report a unique case of CF associated with a primary immunodeficiency syndrome--common variable immunodeficiency (CVID). Our patient has CF, CVID and the additional comorbidity of Aspergers syndrome. The challenges inherent in diagnosing and treating such a case are outlined herein and the successful management of this case is evidenced by the well-preserved lung function of our patient.

Multicentric Castleman's disease in human immunodeficiency virus infection: two case reports.

PubMed

Caroline Ribeiro Sales, Amanda; Romão de Souza Junior, Valter; Iglis de Oliveira, Marta; Azevedo Braga Albuquerque, Claudia; de Barros Campelo Júnior, Evônio; Sérgio Ramos de Araújo, Paulo

2018-05-05

Castleman's Disease is a rare B-cell lymphoproliferative disease. It is mostly benign and is characterized by non-neoplastic lymph node hypertrophy, associated with infection by human herpesvirus-8 in people with the human immunodeficiency virus/acquired immunodeficiency syndrome. Although the unicentric or localized form presents as benign, the multifocal form can manifest severe systemic symptoms. We report two unusual cases of men presenting cervical enlarged lymph nodes that were believed to be infectious. The first case is a 41-year-old feoderm man who presented to the Department of Infectious Diseases of the Hospital das Clínicas in May 2015, with irregular fever history (38-39 °C), dyspnea, weight loss (8 kg/1 year), and asthenia with increased cervical lymph nodes of 1-year duration. His immunohistochemical diagnosis presented Castleman's disease in plasmacytic/diffuse form. In the second case, a 35-year-old feoderm man presented at the same hospital with multiple cervical enlarged lymph nodes and histopathological evidence of Castleman's disease associated with human herpesvirus-8. Considering the importance of differential diagnosis of lymphoid disorders, Castleman's disease is a challenging diagnosis in people living with human immunodeficiency virus/acquired immunodeficiency syndrome and can be easily misdiagnosed when lymphoid disorders are present in the human immunodeficiency virus/acquired immunodeficiency syndrome population due to nonspecific symptoms and signs.

Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus

PubMed Central

Ameratunga, Rohan; Koopmans, Wikke; Woon, See-Tarn; Leung, Euphemia; Lehnert, Klaus; Slade, Charlotte A; Tempany, Jessica C; Enders, Anselm; Steele, Richard; Browett, Peter; Hodgkin, Philip D; Bryant, Vanessa L

2017-01-01

Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID. The proband is heterozygous for the TNFRSF13B/TACI C104R mutation and meets the Ameratunga et al. diagnostic criteria for CVID and the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Her son has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency, but has not inherited the TNFRSF13B/TACI mutation. Her brother, homozygous for the TNFRSF13B/TACI mutation, is in good health despite profound hypogammaglobulinemia and mild cytopenias. We hypothesised that a second unidentified mutation contributed to the symptomatic phenotype of the proband and her son. Whole-exome sequencing of the family revealed a de novo nonsense mutation (T168fsX191) in the Transcription Factor 3 (TCF3) gene encoding the E2A transcription factors, present only in the proband and her son. We demonstrate mutations of TNFRSF13B/TACI impair immunoglobulin isotype switching and antibody production predominantly via T-cell-independent signalling, while mutations of TCF3 impair both T-cell-dependent and -independent pathways of B-cell activation and differentiation. We conclude that epistatic interactions between mutations of the TNFRSF13B/TACI and TCF3 signalling networks lead to the severe CVID-like disorder and SLE in the proband. PMID:29114388

Expression of Essential B Cell Development Genes in Horses with Common Variable Immunodeficiency

PubMed Central

Tallmadge, R.L.; Such, K.A.; Miller, K.C.; Matychak, M.B.; Felippe, M.J.B.

2012-01-01

Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell differentiation or function with inadequate antibody production. Our laboratory studies a natural form of CVID in horses characterized by late-onset B cell lymphopenia due to impaired B cell production in the bone marrow. This study was undertaken to assess the status of B cell differentiation in the bone marrow of CVID-affected horses by measuring the expression of genes essential for early B cell commitment and development. Standard RT-PCR revealed that most of the transcription factors and key signaling molecules that directly regulate B cell differentiation in the bone marrow and precede PAX5 are expressed in the affected horses. Yet, the expression of PAX5 and relevant target genes was variable. Quantitative RT-PCR analysis confirmed that the mRNA expression of E2A, PAX5, CD19, and IGHD was significantly reduced in equine CVID patients when compared to healthy horses (p < 0.05). In addition, the PAX5/EBF1 and PAX5/B220 ratios were significantly reduced in CVID patients (p < 0.01). Immunohistochemical analysis confirmed the absence of PAX5-BSAP expression in the bone marrow of affected horses. Our data suggest that B cell development seems to be impaired at the transition between pre-pro-B cells and pro-B cells in equine CVID patients. PMID:22464097

Newborn screening tests

MedlinePlus

... adrenal hyperplasia Congenital hypothyroidism Cystic fibrosis Fatty acid metabolism disorders Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Human immunodeficiency disease (HIV) Organic acid metabolism disorders Phenylketonuria ( ...

History of Primary Immunodeficiency Diseases in Iran

PubMed Central

Aghamohammadi, Asghar; Moin, Mostafa; Rezaei, Nima

2010-01-01

Pediatric immunology came into sight in the second half of 20th century, when pediatricians and basic immunologists began to give attention to diagnosis and treatment of children with primary immunodeficiency diseases (PIDs). Understanding the genetic and mechanistic basis of PIDs provides unique insight into the functioning of the immune system. By progress in basic and clinical immunology, many infrastructural organizations and academic centers have been established in many countries worldwide to focus on training and research on the immune system and related disorders. Along with progress in basic and clinical immunology in the world, pediatric immunology had a good progress in Iran during the last 33-year period. Now, patients with PIDs can benefit from multidisciplinary comprehensive care, which is provided by clinical immunologists in collaboration with other specialists. Patients with history of recurrent and/or chronic infections suggestive of PIDs are evaluated by standard and research-based testing and receive appropriate treatment. The progress in PIDs can be described in three periods. Development of training program for clinical fellowship in allergy and immunology, multidisciplinary and international collaborative projects, primary immunodeficiency diseases textbooks, meetings on immunodeficiency disorders, improvement in diagnosis and treatment, and construction of Iranian primary immunodeficiency association, Students' research group for immunodeficiencies, Iranian primary immunodeficiency registry, and the immunological societies and centers were the main activities on PIDs during these years. In this article, we review the growth of modern pediatric immunology and PIDs status in Iran. PMID:23056678

Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

ClinicalTrials.gov

2009-10-14

Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

Loss of Retinal Function and Pigment Epithelium Changes in a Patient with Common Variable Immunodeficiency

PubMed Central

Halborg, Jakob; Sørensen, Torben L.

2012-01-01

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. PMID:23056974

Recent incarceration and buprenorphine maintenance treatment outcomes among human immunodeficiency virus-positive patients.

PubMed

Riggins, Daniel P; Cunningham, Chinazo O; Ning, Yuming; Fox, Aaron D

2017-01-01

Opioid use disorder is a common cause of morbidity and mortality among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Buprenorphine maintenance treatment (BMT) is an effective means of therapy, but patients with recent criminal justice involvement may need more support during BMT than other patients. The authors hypothesized that recently incarcerated BMT patients who initiated treatment in primary care would have poorer treatment outcomes than those who were not recently incarcerated. Investigators analyzed data from a multisite cohort study of BMT integrated into HIV care. Patients were stratified by self-reported incarceration in the 30 days before initiation of BMT. The outcomes of interest were 6- and 12-month treatment retention and self-reported opioid use. Investigators used multivariable logistic regression and hierarchical linear model, respectively, to evaluate the association between recent incarceration and these outcomes while adjusting for potential confounding variables. Among 305 BMT patients living with HIV/AIDS, 39 (13%) reported recent incarceration. Patients with recent incarceration (vs. without) were more likely to be homeless, unemployed, and previously diagnosed with mental illness. Recent incarceration was not significantly associated with differences in 6-month (odds ratio [OR] = 0.95; 95% confidence interval [CI] = 0.46-1.98) and 12-month (OR = 0.57; 95% CI = 0.27-1.18) treatment retention or in self-reported opioid use (OR = 0.99; 95% CI = 0.51-1.92) after adjustment for potential confounding variables. Those with incarceration in the 30 days prior to BMT initiation were more likely to be homeless, unemployed, and previously diagnosed with mental illness than those without recent incarceration. However, no significant difference in self-reported opioid use or 6-month or 12-month retention in treatment was detected between those with and without recent incarceration. Future studies should confirm these findings with larger sample sizes. Encouraging formerly incarcerated individuals with opioid use disorder to initiate evidence-based treatments, including BMT, should be part of efforts to confront the opioid addiction epidemic in the United States.

Attentiveness of pediatricians to primary immunodeficiency disorders

PubMed Central

2012-01-01

Background Primary immunodeficiency (PID) is a cluster of serious disorders that requires special alertness on the part of the medical staff for prompt diagnosis and management of the patient. This study explored PID knowledge and experience among pediatricians of wide educational backgrounds, practicing in the United Arab Emirates (UAE). Method A self-administered questionnaire was used to determine the competency of pediatricians in their knowledge of PID disorders. This study questionnaire included questions on PID signs and symptoms, syndromes associated with immunodeficiency, screening tests, interpreting laboratory tests and case management. The participants were 263 pediatricians of diverse education working in the 27 governmental hospitals in all regions of UAE. Results The overall performance of the pediatricians did not differ based on their age, gender, origin of certification, rank, or years of experience. Of the 50 questions, 20% of pediatricians answered correctly <60% of the questions, 76% answered correctly 60 to 79% of the questions, and 4% answered correctly ≥80% of the questions. Seventeen of the 19 PID signs and symptoms were identified by 55 to 97%. Four of 5 syndromes associated with immunodeficiency were identified by 50 to 90%. Appropriate screening tests were chosen by 64 to 96%. Attention to the laboratory reference range values as function of patient age was notably limited. Conclusions There was a noteworthy deficiency in PID work-up. Therefore, implementing effective educational strategies is needed to improve the competency of pediatricians to diagnose and manage PID disorders. PMID:22846098

Psychiatric diagnosis and antiretroviral adherence among adolescent Medicaid beneficiaries diagnosed with human immunodeficiency virus/acquired immunodeficiency syndrome.

PubMed

Walkup, James; Akincigil, Ayse; Bilder, Scott; Rosato, Nancy Scotto; Crystal, Stephen

2009-05-01

Research on adults with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has suggested that psychiatric and substance abuse comorbidities are prevalent in this population, and that these may sometimes be associated with use of antiretroviral therapy (ART) and adherence. For adolescents with HIV/AIDS, much less is known about patterns of mental health comorbidity, and even fewer data are available that compare them to socioeconomically comparable youth without HIV/AIDS. Using medical and pharmacy data from 1999 to 2000 Medicaid claims (Medicaid Analytic Extract) from 4 states for beneficiaries aged 12 to 17 years, we identified 833 youth under care for HIV/AIDS meeting study criteria within the HIV/AIDS group, receipt of ART was less likely for youth who had diagnoses of substance abuse, conduct disorders, or emotional disorders than for others. Once ART was initiated, adherence did not significantly differ between adolescents living with a psychiatric condition, and those who were not, with the exception of an association between conduct disorder and lower adherence. Among those with HIV/AIDS, ART use and adherence were more common among youth with higher rates of service use, regardless of psychiatric status. Associations between race and adherence varied by gender: compared with their white counterparts, minority girls had lower, and minority boys had higher adherence.

Current Perspectives on Primary Immunodeficiency Diseases

PubMed Central

Kumar, Arvind; Teuber, Suzanne S.; Gershwin, M. Eric

2006-01-01

Since the original description of X-linked agammaglobulinemia in 1952, the number of independent primary immunodeficiency diseases (PIDs) has expanded to more than 100 entities. By definition, a PID is a genetically determined disorder resulting in enhanced susceptibility to infectious disease. Despite the heritable nature of these diseases, some PIDs are clinically manifested only after prerequisite environmental exposures but they often have associated malignant, allergic, or autoimmune manifestations. PIDs must be distinguished from secondary or acquired immunodeficiencies, which are far more common. In this review, we will place these immunodeficiencies in the context of both clinical and laboratory presentations as well as highlight the known genetic basis. PMID:17162365

Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

PubMed Central

Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Fischer, Alain; Franco, Jose Luis; Geha, Raif S.; Hammarström, Lennart; Nonoyama, Shigeaki; Notarangelo, Luigi Daniele; Ochs, Hans Dieter; Puck, Jennifer M.; Roifman, Chaim M.; Seger, Reinhard; Tang, Mimi L. K.

2011-01-01

We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases. PMID:22566844

Expression of activation-induced cytidine deaminase gene in B lymphocytes of patients with common variable immunodeficiency.

PubMed

Abolhassani, Hassan; Farrokhi, Amir Salek; Pourhamdi, Shabnam; Mohammadinejad, Payam; Sadeghi, Bamdad; Moazzeni, Seyed-Mohammad; Aghamohammadi, Asghar

2013-08-01

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination (CSR) as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase (AID) protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells (PBMC) of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients (230.95±103.04 ng/ml) rather than controls (210.00±44.72 ng/ml; P=0.5). CVID cases with lower level of AID had decreased total level of IgE (P=0.04) and stimulated IgE production (P=0.02); while cases with increased level of AID presented higher level of IgA (P=0.04) and numbers of B cells (P=0.02) and autoimmune disease (P=0.02). Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients.

Nonhuman primate models of neuro AIDS

PubMed Central

Williams, Rachel; Bokhari, Sirosh; Silverstein, Peter; Pinson, David; Kumar, Anil; Buch, Shilpa

2009-01-01

Human Immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), also manifests neurological complications. HIV-associated dementia (HAD) is the most severe form of HIV-induced neurocognitive disorders. HIV encephalitis (HIVE), the pathological correlate of HAD, is characterized by the formation of multinucleated giant cells and microglial nodules, astrocytosis, and neuronal damage and loss. Pathological evaluation of HAD disease progression in humans is not possible, with the only data collected being from individuals who have succumbed to the disorder, a snap shot of end-stage disease at best. Therefore, pertinent animal models have been developed to alleviate this gap of knowledge in the field of neurovirology and neuroinflammation. In general, the most widely used animal models are the simian immunodeficiency virus (SIV) and the chimeric simian/human immunodeficiency virus (SHIV) macaque model systems. Although both SIV and SHIV model systems are able to potentiate neuroinvasion and the concomitant neuropathology similar to that seen in the human syndromes, the innate differences between the two in disease pathogenesis and progression make for two separate, yet effective, systems for the study of HIV-associated neuropathology. PMID:18780230

Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

PubMed

Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

2014-02-01

Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

[Spectrum of primary immunodeficiencies in a tertiary hospital over a period of 10 years].

PubMed

Martín-Nalda, A; Soler-Palacín, P; Español Borén, T; Caragol Urgelles, I; Díaz de Heredia Rubio, C; Figueras Nadal, C

2011-02-01

More than 200 primary immunodeficiencies (PID) have been described and about 60% present during childhood. Early diagnosis and treatment have been shown to improve patient outcome. Analysis of patients with a PID diagnosed in a paediatric tertiary care hospital-referral centre over a period of 10 years. Medical records of all paediatric patients followed up in our unit were retrospectively reviewed. Clinical and epidemiological features, laboratory tests, therapy and outcome were analysed. One hundred and eighty nine patients were followed up in this period of time. Antibody disorders were the most common diagnosis. In our series, clinical presentation at diagnosis were: recurrent respiratory infections in selective IgA deficiency and common variable immunodeficiency (CVID) patients, failure to thrive and opportunistic infections (mainly viral infections) in patients with severe combined immunodeficiency (SCID), skin abscesses (Staphylococcus aureus, Serratia spp.) and complicated pneumonia (Aspergillus spp., Rhodococcus equi) in chronic granulomatous disease, congenital heart disease and consistent phenotype in 22q11 deletion syndrome, skin abscesses and ecthyma gangrenosum in severe congenital neutropenia and opportunistic infections and sepsis (Pseudomonas aeruginosa) in children with X-linked agammaglobulinaemia (XLA). Lymphoproliferative disorders were common in CVID. No malignancies were observed during this period. One patient with XLA developed chronic encephalitis. All patients with CVID and XLA were receiving immunoglobulin replacement therapy (8 intravenous and 14 (since 2006) subcutaneous route) and in all but two SCID patients, stem cell transplantation was performed. Outcome was good in most of them except 8 SCID (2 prior and 6 after transplantation), 3 Wiskott-Aldrich syndrome, 1 complete DiGeorge, 1 chronic granulomatous disease and 1 ataxia-telangiectasia patients who died during follow-up. The vast majority of patients included in this series presented with typical clinical features; therefore, basic knowledge of these entities in primary care and collaboration with hospital referral centres should allow a large number of PID in children to be diagnosed at an early stage, leading to proper treatment and monitoring, and therefore improvement of patient prognosis. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Genetics Home Reference: Omenn syndrome

MedlinePlus

... cells attack the body's own cells and tissues, accounting for the autoimmune features of Omenn syndrome . Learn ... Immune Response Encyclopedia: Immunodeficiency Disorders Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center ( ...

Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care Hospital.

PubMed

Al-Tamemi, Salem; Naseem, Shafiq Ur Rehman; Al-Siyabi, Nabila; El-Nour, Ibtisam; Al-Rawas, Abdulhakim; Dennison, David

2016-11-01

Primary immunodeficiency (PID) diseases are rare, complex medical disorders that often are overlooked in clinical settings. There are emerging reports of PID from Middle Eastern populations. This study describes the features of PID patients in a tertiary care setting in Oman and compares them with regional and worldwide reports. Sultan Qaboos University Hospital (SQUH) is an academic tertiary care-level hospital for specialized healthcare, including PID patients. At the time of diagnosis, patients' sociodemographics, clinical features, laboratory investigations, and management were entered in electronic form. This study included patients seen between August 2005 and July 2015. One hundred forty patients were registered with a minimum estimated population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median age of onset of symptoms was 8 months, and diagnosis was 21 months with a delay of 13 months. Family history was positive in 44 %, consanguinity was present in 76 %, death of a previous sibling was present in 36 %, and there was an overall mortality in 18 %, with an 85 % probability of survival 10 years following diagnosis. The most common type of immunodeficiency was phagocytic disorders (35.0 %), followed by predominantly antibody disorders (20.7 %), combined immunodeficiency (17.8 %), other well-defined PID syndromes (15.0 %), immune dysregulation syndromes (3.5 %), complement deficiencies (3.5 %), and unclassified immunodeficiency (4.2 %). The commonest presenting infection was pneumonia (47.1 %). PID is not a rare condition in Oman. The prevalence is in concordance with reports from the region but higher than in Western populations. The findings of the current study would help to improve the awareness and management of, and policy making for PID.

Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

ClinicalTrials.gov

2018-02-06

Severe Combined Immunodeficiency (SCID); Immunodeficiency With Predominant T-cell Defect, Unspecified; Severe Chronic Neutropenia; Chronic Granulomatous Disease (CGD); Hyper IgE Syndromes; Hyper IgM Deficiencies; Wiskott-Aldrich Syndrome; Mendelian Susceptibility to Mycobacterial Disease; Common Variable Immune Deficiency (CVID)

Predictive Utility of Brief Alcohol Use Disorders Identification Test (AUDIT) for human immunodeficiency virus antiretroviral medication nonadherence.

PubMed

Broyles, Lauren Matukaitis; Gordon, Adam J; Sereika, Susan M; Ryan, Christopher M; Erlen, Judith A

2011-10-01

Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of 2 cognitive-behavioral ART adherence interventions, the authors sought to determine if results on 2 common alcohol screening tests (Alcohol Use Disorders Identification Test--Consumption [AUDIT-C] and its binge-related question [AUDIT-3]) predict ART nonadherence. Twenty-seven percent of the sample (n = 308) were positive on the AUDIT-C and 34% were positive on the AUDIT-3. In multivariate analyses, AUDIT-C-positive status predicted ART nonadherence after controlling for race, age, conscientiousness, and self-efficacy (P = .036). Although AUDIT-3-positive status was associated with ART nonadherence in unadjusted analyses, this relationship was not maintained in the final multivariate model. The AUDIT-C shows potential as an indirect screening tool for both at-risk drinking and ART nonadherence, underscoring the relationship between alcohol and chronic disease management.

Hemichorea-hemiballismus as an initial manifestation in a Moroccan patient with acquired immunodeficiency syndrome and toxoplasma infection: a case report and review of the literature.

PubMed

Rabhi, Samira; Amrani, Kawthar; Maaroufi, Mustapha; Khammar, Zineb; Khibri, Hajar; Ouazzani, Maha; Berrady, Rhizlane; Tizniti, Siham; Messouak, Ouafae; Belahsen, Faouzy; Bono, Wafaa

2011-01-01

Neurologic signs and symptoms may represent the initial presentation of AIDS in 10-30% of patients. Movement disorders may be the result of direct central nervous system infection by human immunodeficiency virus (HIV) or the result of opportunistic infections. We report the case of a 59 years old woman who had hemichorea-hemiballismus subsequently found to be secondary to a cerebral toxoplasmosis infection revealing HIV infection. Movement disorders, headache and nausea were resolved after two weeks of antitoxoplasmic treatment. Brain MRI control showed a marked resolution of cerebral lesion. Occurrence of hemichorea-ballismus in patient without familial history of movement disorders suggests a diagnosis of AIDS and in particular the diagnosis of secondary cerebral toxoplasmosis. Early recognition is important since it is a treatable entity.

Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

ClinicalTrials.gov

2018-06-20

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

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

PubMed

Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

2016-06-01

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.

Primary immunodeficiency diseases in children treated in the Children's Memorial Hospital, Poland.

PubMed

Bernatowska, E; Madalinski, K; Michalkiewicz, J; Gregorek, H

1988-04-01

One hundred and three cases of primary immunodeficiency diseases were diagnosed among children suffering mainly from chronic and severe infections in the period 1980-1987. Predominantly antibody defects were recognized in 48 patients (46.6%), combined immunodeficiencies in 36 patients (35%), phagocytic disorders in 12 patients (11.6%), complement defects in 6 patients (5.8%), and cell-mediated disease (Di George syndrome) in 1 patient. Allergic complications were observed in 25 patients (24.2%) and malignancy-in 3 patients (2.9%). More detailed immunological studies were performed in children with X-linked agammaglobulinemia in the course of intravenous immunoglobulin therapy and in children with ataxia telangiectasia.

Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.

PubMed

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

2017-10-01

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.

Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India

PubMed Central

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

2017-01-01

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. PMID:28930011

Anxiety symptoms and disorders among adults living with HIV and AIDS: A critical review and integrative synthesis of the empirical literature

PubMed Central

Brandt, Charles; Zvolensky, Michael J.; Woods, Steven P.; Gonzalez, Adam; Safren, Steven A.; O’Cleirigh, Conall M.

2016-01-01

There are over 35 million people worldwide infected with the Human Immunodeficiency Virus (HIV) and its progression to Acquired Immunodeficiency Syndrome (AIDS; WHO, 2014). With the advent of combined antiretroviral therapy (i.e., cART) in 1996, persons living with HIV/AIDS (PLWHA) now have much longer life expectancies. However, living with HIV remains challenging, as it is associated with a number of significant and recurrent (chronic) stressors including physical pain, side effects of cART, social stigma, and discrimination, among other social stressors. Presumably, as a result of these types of stressors, a disproportionately high number of PLWHA struggle with clinically-significant psychiatric symptoms and disorders. Although much scientific and clinical attention has focused on depressed mood and psychopathology among PLWHA, there has been comparably less focus on anxiety and its disorders. The paucity of work in this area is concerning from a public health perspective, as anxiety symptoms and disorders are the most common class of psychiatric disorders and often maintain a large negative impact on life functioning. PMID:27939443

Anxiety symptoms and disorders among adults living with HIV and AIDS: A critical review and integrative synthesis of the empirical literature.

PubMed

Brandt, Charles; Zvolensky, Michael J; Woods, Steven P; Gonzalez, Adam; Safren, Steven A; O'Cleirigh, Conall M

2017-02-01

There are over 35 million people worldwide infected with the Human Immunodeficiency Virus (HIV) and its progression to Acquired Immunodeficiency Syndrome (AIDS; WHO, 2014). With the advent of combined antiretroviral therapy (i.e., cART) in 1996, persons living with HIV/AIDS (PLWHA) now have much longer life expectancies. However, living with HIV remains challenging, as it is associated with a number of significant and recurrent (chronic) stressors including physical pain, side effects of cART, social stigma, and discrimination, among other social stressors. Presumably, as a result of these types of stressors, a disproportionately high number of PLWHA struggle with clinically-significant psychiatric symptoms and disorders. Although much scientific and clinical attention has focused on depressed mood and psychopathology among PLWHA, there has been comparably less focus on anxiety and its disorders. The paucity of work in this area is concerning from a public health perspective, as anxiety symptoms and disorders are the most common class of psychiatric disorders and often maintain a large negative impact on life functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

PubMed

García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

2015-05-01

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Blood disorders typically associated with renal transplantation

PubMed Central

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

Hemichorea-hemiballismus as an initial manifestation in a Moroccan patient with acquired immunodeficiency syndrome and toxoplasma infection: a case report and review of the literature

PubMed Central

Rabhi, Samira; Amrani, Kawthar; Maaroufi, Mustapha; Khammar, Zineb; Khibri, Hajar; Ouazzani, Maha; Berrady, Rhizlane; Tizniti, Siham; Messouak, Ouafae; Belahsen, Faouzy; Bono, Wafaa

2011-01-01

Neurologic signs and symptoms may represent the initial presentation of AIDS in 10-30% of patients. Movement disorders may be the result of direct central nervous system infection by human immunodeficiency virus (HIV) or the result of opportunistic infections. We report the case of a 59 years old woman who had hemichorea-hemiballismus subsequently found to be secondary to a cerebral toxoplasmosis infection revealing HIV infection. Movement disorders, headache and nausea were resolved after two weeks of antitoxoplasmic treatment. Brain MRI control showed a marked resolution of cerebral lesion. Occurrence of hemichorea-ballismus in patient without familial history of movement disorders suggests a diagnosis of AIDS and in particular the diagnosis of secondary cerebral toxoplasmosis. Early recognition is important since it is a treatable entity. PMID:22187591

Bone disorders associated with the human immunodeficiency virus: pathogenesis and management.

PubMed

Qaqish, Roula B; Sims, Keri A

2004-10-01

Bone disorders such as osteopenia, osteoporosis, and osteonecrosis have been reported in patients infected with the human immunodeficiency virus (HIV), but the etiology and mechanism of these disorders are unknown. The prevalence estimates vary widely among studies and may be influenced by the presence or absence of antiretroviral therapy and lipodystrophy, severity of HIV disease, and overlapping bone loss risk factors. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in patients with HIV who have risks for bone disease are important strategies in preventing osteopenia and osteoporosis in HIV-infected patients. Management of osteopenia and osteoporosis is still being evaluated. Administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be reasonable in treating osteoporosis; however, surgical intervention is the only method for treating symptomatic osteonecrosis.

[Chonic diarrhea and malabsorption due to common variable immunodeficiency, gastrectomy and giardiasis infection: a difficult nutritional management].

PubMed

Domínguez-López, M E; González-molero, I; Ramírez-Plaza, C P; Soriguer, F; Olveira, G

2011-01-01

Gastric cancer is a frequent cause of cancer-related mortality in the world. Surgery is the only potentially curative therapy, although the adverse effects of surgery are common and considerable. Common variable immunodeficiency is in many cases cause of gastrointestinal system problems such as chronic diarrhea caused by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of villi leading frequently to malapsortion and malnutrition. Nutritional deficiencies due to malapsorption (postgastrectomy and secondary to loss of villi, giardiasis and common variable inmunodeficiency) are common. We present the case of a patient with gastric cancer who underwent a gastrectomy with common variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with serious diarrhea resistant to treatment and malabsorption.

Changes in B cell immunophenotype in common variable immunodeficiency: cause or effect – is bronchiectasis indicative of undiagnosed immunodeficiency?

PubMed Central

Bright, P; Grigoriadou, S; Kamperidis, P; Buckland, M; Hickey, A; Longhurst, H J

2013-01-01

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

Cognitive Deficits in Psychiatric Patients: Constraints on HIV Prevention.

ERIC Educational Resources Information Center

Tunnell, Gil

Some mental health experts have suggested that particular subgroups of the chronic mentally ill may be especially vulnerable to human immunodeficiency virus (HIV) infection. Patients with mood disorders (manic type), schizophrenia, and dual diagnosis of either disorder with substance abuse are considered at high risk for HIV infection, as are…

Advances in human genetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, H.; Hirschhorn, K.

1993-01-01

This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention,more » to its organ system involvement and molecular biology.« less

Effect of interferon-alpha therapy in a patient with common variable immunodeficiency and chronic Epstein-Barr virus infection.

PubMed

Toraldo, R; D'Avanzo, M; Tolone, C; Canino, G; Iafusco, F; Notarangelo, L D; Ugazio, A; Cirillo, C

1995-01-01

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was detected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-alpha (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-alpha is a valid alternative in therapy of immunodeficient EB virus-infected patients.

Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

PubMed

Kishimoto, Kenji; Kobayashi, Ryoji; Sano, Hirozumi; Suzuki, Daisuke; Maruoka, Hayato; Yasuda, Kazue; Chida, Natsuko; Yamada, Masafumi; Kobayashi, Kunihiko

2014-07-01

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Advances in clinical immunology in 2015.

PubMed

Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

2016-12-01

Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Glycosylation Disorders with Immunodeficiency

MedlinePlus

... Award Negotiation & Initial Award After Award Foreign Grants Management Getting Your Initial International Award Actions You Can Take as the Project Leader on a Foreign Grant Subawards for Foreign ...

Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and monocytopenia.

PubMed

Dotta, Laura; Badolato, Raffaele

2014-10-01

Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey.

PubMed

Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül

2017-12-01

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.

Hematopoietic Stem Cell Therapy as a Counter-Measure for Human Exploration of Deep Space

NASA Technical Reports Server (NTRS)

Ohi, S.; Roach, A.-N.; Ramsahai, S.; Kim, B. C.; Fitzgerald, W.; Riley, D. A.; Gonda, S. R.

2004-01-01

Human exploration of deep space depends, in part, on our ability to counter severe/invasive disorders that astronauts experience in space environments. The known symptoms include hematological/cardiac abnormalities,bone and muscle losses, immunodeficiency, neurological disorders, and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, we have advanced a hypothesis that ome of the space-caused disorders maybe amenable to hematopoietis stem cell therapy(HSCT) so as to maintain promote human exploration of deep space. Using mouse models of human anemia beta-thaiassemia) as well as spaceflight (hindlimb unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, in the case of HSCT for muscle loss, the beta-galactosidese marked HSCs were detected in the hindlimbs of unloaded mouse following transplantation by -X-gal wholemaunt staining procedure. Histochemicaland physical analyses indicated structural contribution of HSCs to the muscle. HSCT for immunodeficiency was investigated ising beta-galactosidese gene-tagged Escherichia coli as the infectious agent. Results of the X-gal staining procedure indicated the rapeutic role of the HSCT. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Neutropenia in primary immunodeficiency

PubMed Central

Sokolic, Robert

2016-01-01

Purpose of review Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely. Recent findings The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option. Summary The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs. PMID:23196894

Prevalence and variables associated with an abnormal ankle-brachial index among patients with human immunodeficiency virus/acquired immunodeficiency syndrome.

PubMed

Hinojosa, Carlos A; Nunez-Salgado, Ana E; Anaya-Ayala, Javier E; Laparra-Escareno, Hugo; Ortiz-Lopez, Laura J; Herrera-Caceres, Jaime O; Crabtree-Ramirez, Brenda E; Sierra-Madero, Juan G

2018-01-01

Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case-control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient's mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome. ClinicalTrials.gov NCT02264509.

Pediatric patients with common variable immunodeficiency: long-term follow-up.

PubMed

Mohammadinejad, P; Aghamohammadi, A; Abolhassani, H; Sadaghiani, M S; Abdollahzade, S; Sadeghi, B; Soheili, H; Tavassoli, M; Fathi, S M; Tavakol, M; Behniafard, N; Darabi, B; Pourhamdi, S; Rezaei, N

2012-01-01

Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. The study population comprised 69 individuals with CVID diagnosed during childhood. The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.

A Cerebellar Tremor in a Patient with Human Immunodeficiency Virus-1 Associated with Progressive Multifocal Leukoencephalopathy

PubMed Central

Kim, Hee-Jin; Lee, Jae-Jung; Lee, Phil Hyu

2009-01-01

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus infection in oligodendrocytes, especially in patients with acquired immunodeficiency syndrome (AIDS). Movement disorders associated with PML are very rare. Here, we report a case of PML in an AIDS patient who presented with a cerebellar tremor, caused by lesions in the cerebellar outflow tract. A cerebellar tremor can be a rare clinical manifestation in patients with PML. PMID:24868366

Medical immunology: two-way bridge connecting bench and bedside.

PubMed

Rijkers, Ger T; Damoiseaux, Jan G M C; Hooijkaas, Herbert

2014-12-01

Medical immunology in The Netherlands is a laboratory specialism dealing with immunological analyses as well as pre- and post-analytical consultation to clinicians (clinical immunologists and other specialists) involved in patients with immune mediated diseases. The scope of medical immunology includes immunodeficiencies, autoimmune diseases, allergy, transfusion and transplantation immunology, and lymphoproliferative disorders plus the monitoring of these patients. The training, professional criteria, quality control of procedures and laboratories is well organized. As examples of the bridge function of medical immunology between laboratory (bench) and patient (bedside) the contribution of medical immunologists to diagnosis and treatment of primary immunodeficiency diseases (in particular: humoral immunodeficiencies) as well as autoantibodies (anti-citrullinated proteins in rheumatoid arthritis) are given. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders.

PubMed

Capello, Daniela; Cerri, Michaela; Muti, Giuliana; Lucioni, Marco; Oreste, Pierluigi; Gloghini, Annunziata; Berra, Eva; Deambrogi, Clara; Franceschetti, Silvia; Rossi, Davide; Alabiso, Oscar; Morra, Enrica; Rambaldi, Alessandro; Carbone, Antonino; Paulli, Marco; Gaidano, Gianluca

2006-12-01

Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n=10; diffuse large B-cell lymphoma, n=35; and Burkitt/Burkitt-like lymphoma, n=5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations.

Advances in Understanding the Pathogenesis of Epstein-Barr Virus-Associated Lymphoproliferative Disorders.

PubMed

Yang, Xi; Nishida, Naonori; Zhao, Xiaodong; Kanegane, Hirokazu

2015-10-01

Epstein-Barr virus (EBV) was discovered 50 years ago from an african Burkitt lymphoma cell line. EBV-associated lymphoproliferative disorders (LPDs) are life- threatening diseases, especially in children. In this article, we review EBV-associated LPDs, especially in the area of primary immunodeficiency disease (PID). We searched PubMed for publications with key words including EBV infection, lymphoma, LPDs and PID, and selected the manuscripts written in English that we judged to be relevant to the topic of this review.On the basis of the data in the literature, we grouped the EBV-associated LPDs into four categories: nonmalignant disease, malignant disease, acquired immunodeficiency disease and PID. Each category has its own risk factor for LPD development. EBV-associated LPD is a complex disease, creating new challenges for diagnosis and treatment.

Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults.

PubMed

Slade, Charlotte A; Bosco, Julian J; Binh Giang, Tran; Kruse, Elizabeth; Stirling, Robert G; Cameron, Paul U; Hore-Lacy, Fiona; Sutherland, Michael F; Barnes, Sara L; Holdsworth, Stephen; Ojaimi, Samar; Unglik, Gary A; De Luca, Joseph; Patel, Mittal; McComish, Jeremy; Spriggs, Kymble; Tran, Yang; Auyeung, Priscilla; Nicholls, Katherine; O'Hehir, Robyn E; Hodgkin, Philip D; Douglass, Jo A; Bryant, Vanessa L; van Zelm, Menno C

2018-01-01

Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency.

PubMed

Kotlarz, Daniel; Ziętara, Natalia; Milner, Joshua D; Klein, Christoph

2014-12-01

This review highlights the recent identification of human interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) deficiencies as novel entities of primary immunodeficiency. We recently described the first patients with IL-21R deficiency who had cryptosporidial infections associated with chronic cholangitis and liver disease. All IL-21R-deficient patients suffered from recurrent respiratory tract infections. Immunological work-up revealed impaired B cell proliferation and immunoglobulin class-switch, reduced T cell effector functions, and variable natural killer cell dysfunctions. Recently, these findings have been extended by the discovery of one patient with a mutation in the IL21 gene. This patient predominantly manifested with very early onset inflammatory bowel disease and recurrent respiratory infections. Laboratory examination showed reduced circulating B cells and impaired B cell class-switch. Human IL-21 and IL-21R deficiencies cause severe, primary immunodeficiency reminiscent of common variable immunodeficiency. Early diagnosis is critical to prevent life-threatening complications, such as secondary liver failure. In view of the critical role of IL-21 in controlling immune homeostasis, early hematopoietic stem cell transplantation might be considered as therapeutic intervention in affected children.

HIV/Sexually Transmitted Infection Risk Behaviors in Delinquent Youth with Psychiatric Disorders: A Longitudinal Study

ERIC Educational Resources Information Center

Elkington, Katherine; Teplin, Linda A.; Mericle, Amy A.; Welty, Leah J.; Romero, Erin G.; Abram, Karen M.

2008-01-01

The effect of psychiatric disorders on human immunodeficiency virus/sexually transmitted infection (HIV/STI) risk behaviors in juvenile justice youths is examined. Prevalence, persistence and prediction are addressed among four mutually exclusive diagnostic groups and results show a high prevalence rate of many HIV/STI sexual risk behaviors that…

Rates and Types of Psychiatric Disorders in Perinatally Human Immunodeficiency Virus-Infected Youth and Seroreverters

ERIC Educational Resources Information Center

Mellins, Claude Ann; Brackis-Cott, Elizabeth; Leu, Cheng-Shiun; Elkington, Katherine S.; Dolezal, Curtis; Wiznia, Andrew; McKay, Mary; Bamji, Mahrukh; Abrams, Elaine J.

2009-01-01

Background: The purpose of this study was to examine 1) the prevalence of psychiatric and substance use disorders in perinatally HIV-infected (HIV+) adolescents and 2) the association between HIV infection and these mental health outcomes by comparing HIV+ youths to HIV exposed but uninfected youths (HIV-) from similar communities. Methods: Data…

Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism

PubMed Central

2013-01-01

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN. Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic neutropenia is a feature of HPS2 and MAPBPIP-deficiency syndrome, whereas it is usually transient in CHS and GS2. In every patient, an accurate diagnosis is required for prompt and appropriate treatment, particularly in patients who develop HLH or in whom bone marrow transplant is required. This review describes the molecular and pathogenetic mechanisms of these diseases, focusing on clinical and biochemical aspects that allow early differential diagnosis. PMID:24134793

B and T cell screen

MedlinePlus

... Cancer of white blood cell called a lymphoblast ( acute lymphoblastic leukemia ) Cancer of white blood cells called ... cell count may be due to: HIV/AIDS Acute lymphoblastic leukemia Immunodeficiency disorders Risks Veins and arteries ...

A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8.

PubMed

Eidenschenk, Celine; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth

2006-04-01

We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus-driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans.

A Novel Primary Immunodeficiency with Specific Natural-Killer Cell Deficiency Maps to the Centromeric Region of Chromosome 8

PubMed Central

Eidenschenk, Céline; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth

2006-01-01

We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus–driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans. PMID:16532402

[Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders].

PubMed

Podzamczer Palter, Daniel; Muñoz-Moreno, José A; Alcolea Rodríguez, Daniel; Alonso Villaverde, Carlos; Antela López, Antonio; Blanch Andreu, Jordi; Casado Osorio, José Luis; Galindo Puerto, M José; Garolera i Freixa, Maite; Locutura Rupérez, Jaime; Lleó Bisa, Albert; Prats París, Anna; Pérez-Valero, Ignacio; Portilla Sogorb, Joaquín; Rovira Cañellas, Alex; Téllez Molina, M Jesús; Tiraboschi, Juan Manuel; Vergara Moragues, Esperanza; Arribas López, José Ramón; Goenaga Sánchez, Miguel Ángel; de León-Naranjo, Fernando Lozano; Martínez Chamorro, Esteban; Polo Rodríguez, Rosa; Muñoz-Moreno, José A; Podzamczer, Daniel

2014-01-01

To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Prevalence and clinical correlates of metabolic syndrome in Nigerians living with human immunodeficiency virus/acquired immunodeficiency syndrome.

PubMed

Ayodele, Olugbenga Edward; Akinboro, Adeolu Oludayo; Akinyemi, Suliat Omolola; Adepeju, Akinlawon Adetiloye; Akinremi, Oluwaseun Akinsanmi; Alao, Christiana Adeola; Popoola, Adetoun Adedayo

2012-10-01

Sub-Saharan Africa bears an inordinate burden of human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS). Reports have shown increased prevalence of clustering of cardiovascular risk factors referred to as metabolic syndrome in treatment-naïve patients and patients on highly active antiretroviral therapy (HAART). In view of the fact that metabolic syndrome is a heterogeneous disorder with substantial variability in the prevalence and component traits within and across populations and the dearth of publications on the prevalence and clinical correlates of metabolic syndrome in people living with HIV/AIDS (PLWHA) in Nigeria, this study was carried out to determine the prevalence and clinical correlates of metabolic syndrome among an HIV-infected outpatient population using the National Cholesterol Education Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS) definitions. We also sought to determine if HAART use and CD4 count level were associated with metabolic syndrome. This cross-sectional study involved 291 (95 men, 196 women) consecutive PLWHA. Anthropometry, blood pressure, fasting plasma glucose, and lipid profile values were determined. The prevalence rates of metabolic syndrome according to the ATP III, IDF, and JIS criteria were 12.7%, 17.2%, and 21.0%, respectively. Metabolic syndrome was significantly associated with female gender (all definitions), body mass index (all definitions), increasing age, and CD4 count (IDF definition). There was no significant association between metabolic syndrome and HAART. The concordance [kappa coefficient (κ)] between the definitions of metabolic syndrome varied between 0.583 and 0.878. The prevalence of metabolic syndrome varied with the criteria used and metabolic syndrome correlates with traditional cardiovascular risk factors rather than HAART-related factors.

Perceptions of One's Neighborhood and Mammogram Use among a Sample of Low-Income Women at Risk for Human Immunodeficiency Virus and Sexually Transmitted Infections.

PubMed

Davey-Rothwell, Melissa A; Bowie, Janice; Murray, Laura; Latkin, Carl A

2016-01-01

Neighborhood disorder, signs of physical and social disorganization, has been related to a range of poor mental and physical health outcomes. Although individual factors have been widely associated with getting a mammogram, little is known about the impact of the neighborhood environment on a woman's decision to get a mammogram. In a sample of women at risk for human immunodeficiency virus and sexually transmitted infections, we explored the role of perceptions of one's neighborhood on getting a mammogram. The study included two samples: women 40 to 49 years (n = 233) and women 50 years and older (n = 83). Data were collected from May 2006 through June 2008. Women age 50 years and older who lived in a neighborhood with disorder were 72% less likely to get a mammogram compared with women who lived in neighborhoods without disorder. There was no relationship for women age 40 to 49 years. Interventions are needed to increase awareness and encourage women living in neighborhoods with disorder to get a mammogram. In addition to interventions to increase mammography, programs are needed to decrease neighborhood disorder. Increasing neighborhood cohesion, social control, and empowerment could integrate health promotion programs to both reduce disorder and increase health behaviors. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome.

PubMed

Levy, Y; Gupta, N; Le Deist, F; Garcia, C; Fischer, A; Weill, J C; Reynaud, C A

1998-10-27

Common Variable Immuno-Deficiency (CVID) is the most common symptomatic primary antibody-deficiency syndrome, but the basic immunologic defects underlying this syndrome are not well defined. We report here that among eight patients studied (six CVID and two hypogammaglobulinemic patients with recurrent infections), there is in two CVID patients a dramatic reduction in Ig V gene somatic hypermutation with 40-75% of IgG transcripts totally devoid of mutations in the circulating memory B cell compartment. Functional assays of the T cell compartment point to an intrinsic B cell defect in the process of antibody affinity maturation in these two cases.

22q11.2 deletion syndrome

PubMed Central

McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

2016-01-01

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita.

PubMed

Parchand, Swapnil; Barwad, Adarsh

2017-01-01

Cytomegalovirus (CMV) retinitis is an opportunistic infection commonly seen in disorders that affect the immune system of the body such as acquired immunodeficiency syndrome and hematological malignancies such as leukemia/lymphoma or organ transplantation. The occurrence of CMV retinitis in the absence of such condition should be thoroughly investigated, as it is a strong indicator of poor immune competence. We here report an interesting case of CMV retinitis as a presenting feature of rare multisystem disorde r "Dyskeratosis congenita."

Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans.

PubMed

Voss, Matthias; Bryceson, Yenan T

2017-04-01

Natural killer (NK) cells are innate immune cytotoxic effector cells well known for their role in antiviral immunity and tumor immunosurveillance. In parts, this knowledge stems from rare inherited immunodeficiency disorders in humans that abrogate NK cell function leading to immune impairments, most notably associated with a high susceptibility to viral infections. Phenotypically, these disorders range from deficiencies selectively affecting NK cells to complex general immune defects that affect NK cells but also other immune cell subsets. Moreover, deficiencies may be associated with reduced NK cell numbers or rather impair specific NK cell effector functions. In recent years, genetic defects underlying the various NK cell deficiencies have been uncovered and have triggered investigative efforts to decipher the molecular mechanisms underlying these disorders. Here we review the associations between inherited human diseases and NK cell development as well as function, with a particular focus on defects in NK cell exocytosis and cytotoxicity. Furthermore we outline how reports of diverse genetic defects have shaped our understanding of NK cell biology. Copyright © 2015. Published by Elsevier Inc.

[Characterization of immune disorders in hemophiliac patients with the identification of inhibitor-dependence in replacement transfusion therapy].

PubMed

Rudenko, V P; Stasyshyn, O V; Lebed', H B; Orlyk, V V; Lohins'kyĭ, V Ie

2001-01-01

Results are analyzed of a clinical observation and examination of 188 patients with haemophilia aged 10-77 years. The haemophilia patients were diagnosed as having developed secondary immunodeficiency related to chronic antigenic stimulation of the patient's immune system by allogenic proteins which contain plasma preparations. Against the background of immunodeficiency, there occur in the patients complications of immune character such as appearance of immune inhibitors to clotting factors. The authors are of the opinion that the nature of the inhibitory form of haemophilia is related, first, to genetic anomalies in factor VIII (IX), which cause the development of the autoimmune process; second, that as a result of alloimmunization and immunomodulating action of substitution therapy there develop persistent disorders in immunoregulation and activation of antibody genesis, which facts come to trigger off the appearance of inhibitory antibodies.

Cold Urticaria, Immunodeficiency, and Autoimmunity Related to PLCG2 Deletions

PubMed Central

Ombrello, Michael J.; Remmers, Elaine F.; Sun, Guangping; Freeman, Alexandra F.; Datta, Shrimati; Torabi-Parizi, Parizad; Subramanian, Naeha; Bunney, Tom D.; Baxendale, Rhona W.; Martins, Marta S.; Romberg, Neil; Komarow, Hirsh; Aksentijevich, Ivona; Kim, Hun Sik; Ho, Jason; Cruse, Glenn; Jung, Mi-Yeon; Gilfillan, Alasdair M.; Metcalfe, Dean D.; Nelson, Celeste; O'Brien, Michelle; Wisch, Laura; Stone, Kelly; Douek, Daniel C.; Gandhi, Chhavi; Wanderer, Alan A.; Lee, Hane; Nelson, Stanley F.; Shianna, Kevin V.; Cirulli, Elizabeth T.; Goldstein, David B.; Long, Eric O.; Moir, Susan; Meffre, Eric; Holland, Steven M.; Kastner, Daniel L.; Katan, Matilda; Hoffman, Hal M.; Milner, Joshua D.

2012-01-01

Background Mendelian analysis of disorders of immune regulation can provide insight into molecular pathways associated with host defense and immune tolerance. Methods We identified three families with a dominantly inherited complex of cold-induced urticaria, antibody deficiency, and susceptibility to infection and autoimmunity. Immunophenotyping methods included flow cytometry, analysis of serum immunoglobulins and autoantibodies, lymphocyte stimulation, and enzymatic assays. Genetic studies included linkage analysis, targeted Sanger sequencing, and next-generation whole-genome sequencing. Results Cold urticaria occurred in all affected subjects. Other, variable manifestations included atopy, granulomatous rash, autoimmune thyroiditis, the presence of antinuclear antibodies, sinopulmonary infections, and common variable immunodeficiency. Levels of serum IgM and IgA and circulating natural killer cells and class-switched memory B cells were reduced. Linkage analysis showed a 7-Mb candidate interval on chromosome 16q in one family, overlapping by 3.5 Mb a disease-associated haplotype in a smaller family. This interval includes PLCG2, encoding phospholipase Cγ2 (PLCγ2), a signaling molecule expressed in B cells, natural killer cells, and mast cells. Sequencing of complementary DNA revealed heterozygous transcripts lacking exon 19 in two families and lacking exons 20 through 22 in a third family. Genomic sequencing identified three distinct in-frame deletions that cosegregated with disease. These deletions, located within a region encoding an autoinhibitory domain, result in protein products with constitutive phospholipase activity. PLCG2-expressing cells had diminished cellular signaling at 37°C but enhanced signaling at subphysiologic temperatures. Conclusions Genomic deletions in PLCG2 cause gain of PLCγ2 function, leading to signaling abnormalities in multiple leukocyte subsets and a phenotype encompassing both excessive and deficient immune function. (Funded by the National Institutes of Health Intramural Research Programs and others.) PMID:22236196

Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.

PubMed

Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L

2014-01-01

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. © 2013 Wiley Periodicals, Inc.

Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency.

PubMed

Tuckett, Andrea Z; Thornton, Raymond H; O'Reilly, Richard J; van den Brink, Marcel R M; Zakrzewski, Johannes L

2017-05-16

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 IL2rγ null mice is feasible and facilitates the generation of functional T cells conferring protective immunity. 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 IL2rγ null 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 IL2rγ null mice was assessed in a B cell lymphoma model. Despite the small size of the thymic remnant in NOD-scid IL2rγ null 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 IL2rγ null mice displayed anti-lymphoma activity in vivo, but we found no evidence for severe auto/alloreactivity in T cell-producing NOD-scid IL2rγ null mice, suggesting that immune dysregulation is not a major concern. Our findings suggest that intrathymic injection of donor hematopoietic stem and progenitor cells is a safe and effective strategy to establish protective T cell immunity in a mouse model of severe combined immunodeficiency.

Influenza Vaccination in Patients with Common Variable Immunodeficiency (CVID).

PubMed

Mieves, Jan F; Wittke, Kirsten; Freitag, Helma; Volk, Hans-Dieter; Scheibenbogen, Carmen; Hanitsch, Leif G

2017-10-05

Vaccination against influenza in patients with primary antibody deficiency is recommended. Common variable immunodeficiency (CVID) is the most frequent and clinically relevant antibody deficiency disease and is by definition characterized by an impaired vaccination response. The purpose of this review is to present the current knowledge of humoral and cellular vaccine response to influenza in CVID patients. Studies conducted in CVID patients demonstrated an impaired humoral response upon influenza vaccination. Data on cellular immune response are in part conflicting, with two out of three studies showing responses similar to healthy controls. Available data suggest a benefit from influenza vaccination in CVID patients. Therefore, annual influenza vaccination in patients and their close household contacts is recommended.

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

NASA Astrophysics Data System (ADS)

Ohi, Seigo; Roach, Allana-Nicole; Ramsahai, Shweta; Kim, Bak C.; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

2004-02-01

Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from β-galactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine.

PubMed Central

Mukand, J. A.

1991-01-01

Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. PMID:1866948

Comprehensive genetic testing for primary immunodeficiency disorders in a tertiary hospital: 10-year experience in Auckland, New Zealand.

PubMed

Woon, See-Tarn; Ameratunga, Rohan

2016-01-01

New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs). Since 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014. We undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity. Thorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.

Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management.

PubMed

Vince, Nicolas; Mouillot, Gaël; Malphettes, Marion; Limou, Sophie; Boutboul, David; Guignet, Angélique; Bertrand, Véronique; Pellet, Philippe; Gourraud, Pierre-Antoine; Debré, Patrice; Oksenhendler, Eric; Théodorou, Ioannis; Fieschi, Claire

2018-04-27

The precise diagnosis of an immunodeficiency is sometimes difficult to assess, especially due to the large spectrum of phenotypic variation reported among patients. Common variable immunodeficiency disorders (CVID) do not have, for a large part, an identified genetic cause. The identification of a causal genetic mutation is important to confirm, or in some cases correct, the diagnosis. We screened >150 male patients with hypogammaglobulinemia for mutations in three genes involved in pediatric X-linked primary immunoglobulin deficiency: CD40LG, SH2D1A and BTK. The SH2D1A screening allowed to reclassify two individuals with an initial CVID presentation as XLP after mutations identification. All these mutations were associated with a lack of protein expression. In addition, 4 patients with a primary diagnosis of CVID and one with a primary IgG subclass deficiency were requalified as XLA after identifying BTK mutations. Interestingly, two out of these 5 patients carried a damaging coding BTK mutation associated with a lower, but detectable, BTK expression in monocytes, suggesting that a dysfunctional protein explains the disease phenotype in these patients. In conclusion, our results advocate to include SH2D1A and BTK in newly developed targeted NGS genetic testing, to contribute to providing the most appropriate medical treatment and genetic counselling. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Short stature/short limb skeletal dysplasia with severe combined immunodeficiency and bowing of the femora: report of two patients and review.

PubMed Central

MacDermot, K D; Winter, R M; Wigglesworth, J S; Strobel, S

1991-01-01

We report two patients with severe combined immunodeficiency and short stature/short limb skeletal dysplasia. Case 1 presented at birth with rhizomelic shortening of the extremities and bowing of the femora. She developed clinical signs of severe combined immunodeficiency at 13 months and died at 21 months. Case 2 had severe prenatal shortening and bowing of the extremities and a small, malformed chest. Symptoms of severe combined immunodeficiency and severe failure to thrive developed soon after birth and she died at 5 months. The diagnosis of severe combined immunodeficiency in our patients was based on their clinical course and necropsy findings, supported in case 1 by the results of immune function tests. The results of investigation of immune function (immunoglobulins, lymphocyte subpopulations, lymphocyte function) are very variable in this syndrome as in other variants of severe combined immunodeficiency. Bone histopathology in both patients showed grossly irregular costochondral junctions, but normal transition of proliferating to hypertrophic chondrocytes. These cases belong to early lethal type 1 short limb skeletal dysplasia with severe combined immunodeficiency. Review of previously published cases with severe combined immunodeficiency and well documented skeletal findings show eight patients with prenatal onset of bowing and shortening of the extremities and metaphyseal abnormalities. These include two sib pairs concordant for the skeletal changes. In these cases, adenosine deaminase levels were not reported. An additional four published cases with associated adenosine deaminase deficiency had only mild metaphyseal abnormalities, but subsequently showed no linear growth.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1999827

Inflammatory Bowel Disease in Primary Immunodeficiencies.

PubMed

Kelsen, Judith R; Sullivan, Kathleen E

2017-08-01

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.

Pneumococcal vaccine failure: can it be a primary immunodeficiency?

PubMed

Moinho, Rita; Brett, Ana; Ferreira, Gisela; Lemos, Sónia

2014-06-12

Vaccine failure is a rare condition and the need to investigate a primary immunodeficiency is controversial. We present the case of a 4-year-old boy, with complete antipneumococcal vaccination, who had necrotising pneumonia with pleural effusion and severe pancytopaenia with need for transfusion. A vaccine-serotype Streptococcus pneumoniae was isolated in the blood culture. On follow-up, detailed medical history, laboratory and genetic investigation led to the diagnosis of X linked dyskeratosis congenita. Dyskeratosis congenita is an inherited disorder that causes shortening or dysfunction of telomeres, affecting mainly rapidly dividing cells (particularly in the skin and haematopoietic system). It leads to bone marrow failure, combined immunodeficiency and predisposition to cancer. The confirmation of this diagnosis allows genetic counselling and medical monitoring of these patients, in order to detect early complications such as bone marrow aplasia or malignancies. 2014 BMJ Publishing Group Ltd.

Impaired Akt phosphorylation in B-cells of patients with common variable immunodeficiency.

PubMed

Yazdani, Reza; Ganjalikhani-Hakemi, Mazdak; Esmaeili, Mohammad; Abolhassani, Hassan; Vaeli, Shahram; Rezaei, Abbas; Sharifi, Zohre; Azizi, Gholamreza; Rezaei, Nima; Aghamohammadi, Asghar

2017-02-01

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency characterized by recurrent infections. We evaluated whether defective PI3K/Akt/FoxO pathway could influence B-cell fate. Determination of B-cell subsets in CVD patients and healthy donors (HDs) were performed using flow cytometry. We evaluated mRNA and protein expression of PI3K, Akt and FoxO using real-time PCR and flow cytometry, respectively. Moreover, phosphorylated Akt (pAkt) expression in B-cells has been measured by flowcytometry. We identified a significant reduction in the percentage of marginal zone like B-cells, memory B-cells (total, switched and unswitched) and plasmablasts in patients, as these decreased B-cell subsets had a significant negative correlation with increased apoptosis in patients. Surprisingly, we identified decreased pAkt expression in B-cells of patients than HDs. We described for the first time impaired pAkt expression in B-cells of CVID patients that had a significant correlation with antibody response to the vaccine and worse clinical complications. Copyright © 2016 Elsevier Inc. All rights reserved.

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

NASA Technical Reports Server (NTRS)

Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

2003-01-01

It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases

PubMed Central

Sağ, Erdal; Gönç, Nazlı; Alikaşifoğlu, Ayfer; Kuşkonmaz, Barış; Uçkan, Duygu; Özön, Alev; Kandemir, Nurgün

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation. PMID:26777050

Common Variable Immunodeficiency (CVID)

MedlinePlus

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Cutaneous cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.

PubMed

AbdullGaffar, Badr; Raman, Lakshmiah G; Al Muala, Alia

2008-09-01

Abstract Cytomegalovirus (CMV) infection in immunocompromised patients is a common opportunistic systemic infection which can lead to death, and usually presents with visceral manifestations, especially of the lung, brain, eye, and gastrointestinal tract. Cutaneous CMV infection is, however, relatively rare in immunocompromised patients. Cutaneous CMV infection can have variable clinical and histologic manifestations, and thus can be easily missed. We report a case of cutaneous CMV infection in a patient with acquired immunodeficiency syndrome, presenting as a generalized, pruritic, erythematous, maculopapular eruption.

Prevalence of atopic disorders and immunodeficiency in patients with ectodermal dysplasia syndromes

PubMed Central

Mark, Barry J.; Becker, Bradley A.; Halloran, Donna R.; Bree, Alanna F.; Sindwani, Raj; Fete, Mary D.; Motil, Kathleen J.; Srun, Sopheak W.; Fete, Timothy J.

2013-01-01

Background Ectodermal dysplasia (ED) syndromes are a diverse group of disorders that affect multiple ectodermally derived tissues. Small studies and case reports suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients with ED syndromes. Objective To determine the prevalence of clinical symptoms suggestive of atopy or immunodeficiency among a large cohort of children with ED syndromes. Methods A 9-page questionnaire was mailed to families who were members of the National Foundation for Ectodermal Dysplasias. The surveys were completed by parents of children younger than 18 years with a diagnosis of an ED syndrome or carrier state. Portions of the questionnaire were adapted from previously validated questionnaires developed by the International Study of Asthma and Allergies in Childhood (ISAAC). Results We received 347 completed questionnaires (41%). When compared with the 13- to 14-year-old children surveyed by ISAAC, we found both all-aged and age-matched children with ED syndromes, respectively, had significantly higher rates of asthma (32.2% and 37.2% vs 16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9% vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs (6.1%) in these ED patients also exceeded known rates in the general pediatric population. Conclusion This large-scale, retrospective study demonstrates a greater reported prevalence of symptoms suggestive of atopic disorders and PIDs among children with ED syndromes than the general pediatric population. A combination of genetic and environmental factors in ED syndromes may contribute to breaches of skin and mucosal barriers, permitting enhanced transmission and sensitization to irritants, allergens, and pathogens. PMID:22626597

An endoscopic and pathological survey of digestive tract disorders in patients infected with human immunodeficiency virus monitored in the Clinic of Infectious Diseases from Tirgu Mures, Romania.

PubMed

Sincu, Nina-Ioana; Mocan, Simona; Chiriac, Lucia Carmen; Băţagă, Simona

2014-01-01

Gastrointestinal symptoms are among the most frequent complaints of patients infected with human immunodeficiency virus (HIV). An endoscopic and histopathological survey of digestive tract diseases among HIV-infected patients monitored in the Clinic of Infectious Diseases I from Tirgu Mures, Romania. Retrospective, observational study, on a group of 38 HIV-positive patients admitted to the Clinic of Infectious Diseases I from Tirgu Mures, Romania, during 2006-2013, undergoing upper/lower endoscopy. We collected data regarding the results of endoscopy and histopathological examination, CD4+ T-lymphocytes levels, microbiological examinations and outcome. Statistical analysis, performed by using Microsoft Office Excel 2007 and GraphPad Prism 5 programs, included contingency tables analysis and comparing means. Our study depicted a variety of digestive disorders among HIV-infected patients, ranging from opportunistic infections to HIV enteropathy and non-HIV-associated conditions. The presence of Candida esophagitis implied significantly lower levels of CD4+ T-cells (p=0.0043). We found a statistically significant negative association between antiretroviral therapy and the presence of opportunistic infections (p=0.0375, OR=0.2030, 95% CI 0.0423-0.9741). Thirteen (34.21%) patients died, mostly due to tuberculosis and central nervous system infections. All were diagnosed with acquired immunodeficiency syndrome (AIDS). HIV-infected patients experience a wide variety of digestive tract disorders, both AIDS-defining illnesses and non-HIV-associated conditions. Gastrointestinal opportunistic infections occur more often among patients with low CD4+ T-cells levels and in those not receiving antiretroviral therapy. Although digestive conditions did not represent direct causes of death in our study, they may predict an unfavorable outcome in AIDS-stage patients.

Rapid Flow cytometric prenatal diagnosis of primary immunodeficiency (PID) disorders.

PubMed

Mishra, Anju; Gupta, Maya; Dalvi, Aparna; Ghosh, Kanjaksha; Madkaikar, Manisha

2014-04-01

Primary Immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders of immune system. Immunophenotypic evaluation of PIDs using flowcytometry provides important clues for diagnosis of these disorders, though confirmation requires identification of underlying molecular defects. Prenatal diagnosis (PND) forms an important component of management in families affected with severe PID. However, molecular diagnostic facilities for each of these diseases are not available and may not be possible to perform in all cases. In such scenario we opted for phenotypic prenatal diagnosis by cordocentesis for families with index case having immunophenotypically well characterized PID. Normal reference ranges of lymphocyte subsets, CD 18/CD11 integrins on leukocytes, MHC class II expression and oxidative burst activity of fetal neutrophils at 18 weeks of gestation were previously established on 30 cord blood samples. PND was performed in 13 families with PIDs. Maternal contamination was ruled out by VNTR analysis. Out of 13 fetuses, nine were found to be unaffected (three cases with leukocyte adhesion deficiency (LAD-I), four cases with severe combined immunodeficiency diseases (SCID), one with X-linked agammaglobulinemia (XLA), and one with chronic granulomatous disease (CGD)] and three were found to be affected (one with T-B+NK-SCID, one with MHC class II deficiency and one with LAD-I). Diagnosis was confirmed by testing the cord blood samples after delivery and further follow-up of the children. In one family diagnosis could not be offered due to maternal contamination. No procedure related complications were observed. Flowcytometry offers rapid and sensitive method for prenatal diagnosis and genetic counseling for selected phenotypically well characterized PID in cases where molecular diagnostic facilities are not available.

Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS).

PubMed

Matas, Carla Gentile; Leite, Renata Aparecida; Magliaro, Fernanda Cristina Leite; Gonçalves, Isabela Crivellaro

2006-08-01

We examined the peripheral auditory system and the auditory brainstem pathway of children with Acquired Immunodeficiency Syndrome (AIDS). One hundred and one children, 51 with AIDS diagnosis and 50 normal children were evaluated. Audiological assessment included immittance measures, pure tone and speech audiometry and auditory brainstem response (ABR). The children with AIDS more frequently had abnormal results than did their matched controls, presenting either peripheral or auditory brainstem impairment. We suggest that AIDS be considered a risk factor for peripheral and/or auditory brainstem disorders. Further research should be carried out to investigate the auditory effects of HIV infection along the auditory pathway.

Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil.

PubMed

Errante, Paolo Ruggero; Perazzio, Sandro Félix; Frazão, Josias Brito; da Silva, Neusa Pereira; Andrade, Luis Eduardo Coelho

2016-01-01

Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott-Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4(+) lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Immunodeficiency with thymoma: failure to induce Ig production in immunodeficient lymphocytes cocultured with normal T cells. [X radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litwin, S.D.

Blood mononuclear cells of two individuals having immunodeficiency with thymoma (ID-THY) were cocultured with normal mononuclear cells or treated mononuclear cell fractions in an attempt to correct an imbalance of regulatory cells postulated to be responsible for the failure of pokeweed mitogen-induced Ig synthesis in vitro. Treatment included abrogation of suppressor cell activity by irradiation or incubation with prednisolone in vitro. T cell help was provided by cocultivating lymphocytes of related and unrelated persons, and in some cases autologous treated cells. Ig secretion failed to be induced by any experimental maneuver suggesting that the primary problem in the above ID-THYmore » cells was related to defective or deficient B cells rather than an imbalance of T regulatory cells. Prednisolone treatment in vitro decreased suppressor cell activity in allogeneic cocultures of two ID-THY persons (S1 and S2) but not of an individual (S3) with variable immunodeficiency suggesting heterogeneity of suppressor cells.« less

Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

PubMed

Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

2010-07-08

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

[The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (AIDS) patients].

PubMed

Spinola-Castro, Angela Maria; Siviero-Miachon, Adriana A; da Silva, Marcos Tadeu Nolasco; Guerra-Junior, Gil

2008-07-01

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Vaccine-derived poliomyelitis 12 years after infection in Minnesota.

PubMed

DeVries, Aaron S; Harper, Jane; Murray, Andrew; Lexau, Catherine; Bahta, Lynn; Christensen, Jaime; Cebelinski, Elizabeth; Fuller, Susan; Kline, Susan; Wallace, Gregory S; Shaw, Jing H; Burns, Cara C; Lynfield, Ruth

2011-06-16

A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.

Classical Hodgkin lymphoma arising in the setting of iatrogenic immunodeficiency: a clinicopathologic study of 10 cases.

PubMed

Loo, Eric Y; Medeiros, L Jeffrey; Aladily, Tariq N; Hoehn, Daniela; Kanagal-Shamanna, Rashmi; Young, Ken H; Lin, Pei; Bueso-Ramos, Carlos E; Manning, John T; Patel, Keyur; Thomazy, Vilmos; Brynes, Russell K; Goswami, Maitrayee; Fayad, Luis E; Miranda, Roberto N

2013-08-01

Iatrogenic immunodeficiency-associated lymphoproliferative disorders are rare. A small subset of these lesions resembles classical Hodgkin lymphoma (CHL), but there are few data in the literature about these lesions. We describe 10 patients with autoimmune diseases treated with immunomodulator therapeutic agents who developed CHL. The autoimmune diseases included rheumatoid arthritis (n=5), systemic lupus erythematosus (n=2), dermatomyositis (n=1), autoimmune hepatitis (n=1), and Crohn disease (n=1), and the immunomodulatory therapies were methotrexate, azathioprine, tumor necrosis factor-α inhibitors, and thalidomide alone or in various combinations. The study group included 9 women and 1 man with a median age of 50 years (range, 25 to 77 y). The histologic features supported CHL in all cases with Reed-Sternberg (RS) and Hodgkin (H) cells in an inflammatory cell background, although the neoplasm could only be subclassified in 3 patients: 2 nodular sclerosis and 1 mixed cellularity. Immunohistochemical analysis supported the diagnosis of CHL. In all cases the RS-H cells were CD30. Nine of 10 cases were CD15, whereas CD20 was expressed variably in 4/10 cases. CD45/LCA was negative in 8 cases assessed. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in the RS-H cells in 8/10 cases. The microenvironment of these lesions depicted a predominance of T-regulatory cells and M2 histiocytes. Clinical follow-up data were available for 7 patients, with a median posttreatment period of 27 months (range, 12 mo to 7 y). In all 7 patients immunomodulatory drug therapy was discontinued, and chemotherapy for CHL was administered; 2 patients also received local radiation. All 7 patients achieved complete remission and are alive. We conclude that iatrogenic immunodeficiency-associated CHL is highly associated with Epstein-Barr virus infection, and patients usually have a good outcome after discontinuation of immunomodulatory agents and chemotherapy for CHL.

The Cognitive and Behavioural Phenotype of Roifman Syndrome

ERIC Educational Resources Information Center

de Vries, P. J.; McCartney, D. L.; McCartney, E.; Woolf, D.; Wozencroft, D.

2006-01-01

Background: Roifman syndrome (OMIM 300258) is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman…

Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications

PubMed Central

Siegfried, Elaine C.; Hebert, Adelaide A.

2015-01-01

Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD. These include inflammatory skin conditions, infections, infestations, malignancies, genetic disorders, immunodeficiency disorders, nutritional disorders, graft-versus-host disease, and drug eruptions. Familiarity of the spectrum of these diseases and their distinguishing features is critical for correct and timely diagnosis and optimal treatment. PMID:26239454

Amount of HIV DNA in Peripheral Blood Mononuclear Cells is Proportional to the Severity of HIV-1-Associated Neurocognitive Disorders

PubMed Central

Shiramizu, Bruce; Williams, Andrew E.; Shikuma, Cecilia; Valcour, Victor

2009-01-01

Human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells was previously associated with neuropsychological function. By including individuals encompassing the full range of HIV-1-associated neurocognitive disorders, this study reports results from subjects with normal cognition, minor cognitive motor disorder, and HIV-1-associated dementia. Individuals with normal cognition had relatively low HIV DNA levels compared to those with minor cognitive motor disorder and HIV-1-associated dementia. Neuropsychological deficits were significantly associated with entry HIV DNA in all domains. These findings demonstrate for the first time that the severity of HIV-1-associated neurocognitive disorders is proportional to the amount of circulating HIV DNA. PMID:19359454

Cytokine Polymorphisms are Associated with Poor Sleep Maintenance in Adults Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

PubMed Central

Lee, Kathryn A.; Gay, Caryl; Pullinger, Clive R.; Hennessy, Mary Dawn; Zak, Rochelle S.; Aouizerat, Bradley E.

2014-01-01

Study Objectives: Cytokine activity and polymorphisms have been associated with sleep outcomes in prior animal and human research. The purpose of this study was to determine whether circulating plasma cytokines and cytokine polymorphisms are associated with the poor sleep maintenance commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Design: Cross-sectional descriptive study. Setting: HIV clinics and community sites in the San Francisco Bay area. Participants: A convenience sample of 289 adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS. Interventions: None. Measurements and Results: A wrist actigraph was worn for 72 h to estimate the percentage of wake after sleep onset (WASO%) and total sleep time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for demographic variables such as race and sex, and clinical variables such as CD4+ count and medications, higher WASO% was associated with single nucleotide polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also associated with short sleep duration. Conclusions: This study strengthens the evidence for an association between inflammation and sleep maintenance problems. In this chronic illness population, cytokine polymorphisms associated with wake after sleep onset provide direction for intervention research aimed at comparing anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance and total sleep time. Citation: Lee KA; Gay C; Pullinger CR; Hennessy MD; Zak RS; Aouizerat BE. Cytokine polymorphisms are associated with poor sleep maintenance in adults living with human immunodeficiency virus/acquired immunodeficiency syndrome. SLEEP 2014;37(3):453-463. PMID:24587567

Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency.

PubMed

Whitmore, Kathryn V; Gaspar, Hubert B

2016-01-01

Adenosine deaminase (ADA) deficiency is best known as a form of severe combined immunodeficiency (SCID) that results from mutations in the gene encoding ADA. Affected patients present with clinical and immunological manifestations typical of a SCID. Therapies are currently available that can target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidence that deficiency of ADA has significant impact on non-immunological organ systems. This review will outline the impact of ADA deficiency on various organ systems, starting with the well-understood immunological abnormalities. We will discuss possible pathogenic mechanisms and also highlight ways in which current treatments could be improved. In doing so, we aim to present ADA deficiency as more than an immunodeficiency and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems. Only by fully understanding ADA deficiency and its manifestations in all organ systems can we aim to deliver therapies that will correct all the clinical consequences.

Adenosine Deaminase Deficiency – More Than Just an Immunodeficiency

PubMed Central

Whitmore, Kathryn V.; Gaspar, Hubert B.

2016-01-01

Adenosine deaminase (ADA) deficiency is best known as a form of severe combined immunodeficiency (SCID) that results from mutations in the gene encoding ADA. Affected patients present with clinical and immunological manifestations typical of a SCID. Therapies are currently available that can target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidence that deficiency of ADA has significant impact on non-immunological organ systems. This review will outline the impact of ADA deficiency on various organ systems, starting with the well-understood immunological abnormalities. We will discuss possible pathogenic mechanisms and also highlight ways in which current treatments could be improved. In doing so, we aim to present ADA deficiency as more than an immunodeficiency and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems. Only by fully understanding ADA deficiency and its manifestations in all organ systems can we aim to deliver therapies that will correct all the clinical consequences. PMID:27579027

Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature.

PubMed

McCann, Liza J; McPartland, Jo; Barge, Dawn; Strain, Lisa; Bourn, David; Calonje, Eduardo; Verbov, Julian; Riordan, Andrew; Kokai, George; Bacon, Chris M; Wright, Michael; Abinun, Mario

2014-01-01

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.

Anti-HIV Drugs Decrease the Expression of Matrix Metalloproteinases in Astrocytes and Microglia

ERIC Educational Resources Information Center

Liuzzi, G. M.; Mastroianni, C. M.; Latronico, T.; Mengoni, F.; Fasano, A.; Lichtner, M.; Vullo, V.; Riccio, P.

2004-01-01

The introduction of potent antiretroviral drugs for the treatment of patients with human immunodeficiency virus (HIV) infection has dramatically reduced the prevalence of HIV-associated neurological disorders. Such diseases can be mediated by proteolytic enzymes, i.e. matrix metalloproteinases (MMPs) and, in particular gelatinases, released from…

HIV and Communication

ERIC Educational Resources Information Center

McNeilly, L.G.

2005-01-01

The human immunodeficiency virus (HIV) continues to plague many countries across the globe, including the United States, Africa, China and India. Children and adults have been infected with HIV, and both populations can present with communication disorders that coexist with the presence of the virus. The purpose of this paper is to present an…

Effectiveness Trial of Community-Based I Choose Life-Africa Human Immunodeficiency Virus Prevention Program in Kenya

PubMed Central

Adam, Mary B.

2014-01-01

We measured the effectiveness of a human immunodeficiency virus (HIV) prevention program developed in Kenya and carried out among university students. A total of 182 student volunteers were randomized into an intervention group who received a 32-hour training course as HIV prevention peer educators and a control group who received no training. Repeated measures assessed HIV-related attitudes, intentions, knowledge, and behaviors four times over six months. Data were analyzed by using linear mixed models to compare the rate of change on 13 dependent variables that examined sexual risk behavior. Based on multi-level models, the slope coefficients for four variables showed reliable change in the hoped for direction: abstinence from oral, vaginal, or anal sex in the last two months, condom attitudes, HIV testing, and refusal skill. The intervention demonstrated evidence of non-zero slope coefficients in the hoped for direction on 12 of 13 dependent variables. The intervention reduced sexual risk behavior. PMID:24957544

Effectiveness trial of community-based I Choose Life-Africa human immunodeficiency virus prevention program in Kenya.

PubMed

Adam, Mary B

2014-09-01

We measured the effectiveness of a human immunodeficiency virus (HIV) prevention program developed in Kenya and carried out among university students. A total of 182 student volunteers were randomized into an intervention group who received a 32-hour training course as HIV prevention peer educators and a control group who received no training. Repeated measures assessed HIV-related attitudes, intentions, knowledge, and behaviors four times over six months. Data were analyzed by using linear mixed models to compare the rate of change on 13 dependent variables that examined sexual risk behavior. Based on multi-level models, the slope coefficients for four variables showed reliable change in the hoped for direction: abstinence from oral, vaginal, or anal sex in the last two months, condom attitudes, HIV testing, and refusal skill. The intervention demonstrated evidence of non-zero slope coefficients in the hoped for direction on 12 of 13 dependent variables. The intervention reduced sexual risk behavior. © The American Society of Tropical Medicine and Hygiene.

Incidence and Long-term Outcomes of the HIV-Neuroretinal Disorder in Patients with the Acquired Immunodeficiency Syndrome

PubMed Central

Jabs, Douglas A.; Drye, Lea; Van Natta, Mark L.; Thorne, Jennifer E.; Holland, Gary N.

2014-01-01

Objectives Patients with the acquired immunodeficiency syndrome (AIDS) have an abnormality of retina/optic nerve function, manifested as decreased contrast sensitivity (in the absence of ocular opportunistic infections or media opacity), abnormalities on automated perimetry, and loss of retinal nerve fiber layer, even among those with good visual acuity, termed the HIV-neuroretinal disorder. The objectives of this study were to determine the prevalence, incidence, risk factors for, and outcomes of HIV-neuroretinal disorder. Design Prospective cohort study Participants 1822 patients with AIDS without ocular infections or media opacities. Methods Patients with HIV-neuroretinal disorder were identified by a contrast sensitivity < 1.50 log units in either eye in the absence of ocular opportunistic infections or media opacity. Main outcome measures Incidence of HIV-neuroretinal disorder, mortality, visual impairment (visual acuity 20/50 or worse), and blindness (20/200 or worse) on logarithmic visual acuity charts. Results Sixteen percent of participants had HIV-neuroretinal disorder at enrollment. The estimated cumulative incidence by 20 years after AIDS diagnosis was 51% (95% confidence interval [CI] 46%–55%). HIV-neuroretinal disorder was more common in women and African American persons. Risk factors for it included hepatitis C infection, low CD4+ T cells, and detectable HIV RNA in the blood. Patients with HIV neuroretinal disorder had a 70% excess mortality vs. those without it, even after adjusting for CD4+ T cells and HIV load (hazard ratio=1.7, 95% CI= 1.3–2.1, P<0.0001). Patients with HIV-neuroretinal disorder had increased risks of bilateral visual impairment (hazard ratio=6.5, 95% CI=2.6–10.6, P<0.0001) and blindness (hazard ratio=5.9, 95% CI=2.8–13.7, P=0.01) vs. those without HIV neuroretinal disorder. Conclusions HIV-neuroretinal disorder is a common finding among patients with AIDS, and it is associated with an increased mortality and an increased risk of visual impairment. Successful antiretroviral therapy decreases but does not eliminate the risk of HIV-neuroretinal disorder. PMID:25600199

How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease?

PubMed

Arslan, Sevket; Ucar, Ramazan; Caliskaner, Ahmet Zafer; Reisli, Ismail; Guner, Sukru Nail; Sayar, Esra Hazar; Baloglu, Ismail

2016-02-01

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.

Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study.

PubMed

Hamidieh, A A; Behfar, M; Pourpak, Z; Faghihi-Kashani, S; Fazlollahi, M R; Hosseini, A S; Movahedi, M; Mozafari, M; Moin, M; Ghavamzadeh, A

2016-02-01

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

Not all SCID pigs are created equally: Two independent mutations in the Artemis gene cause Severe Combined Immunodeficiency (SCID) in pigs

PubMed Central

Waide, Emily H; Dekkers, Jack CM; Ross, Jason W; Rowland, Raymond RR; Wyatt, Carol R; Ewen, Catherine L; Evans, Alyssa B; Thekkoot, Dinesh M; Boddicker, Nicholas J; Serão, Nick VL; Ellinwood, N Matthew; Tuggle, Christopher K

2017-01-01

Mutations in over 30 genes are known to result in impairment of the adaptive immune system, causing a group of disorders collectively known as severe combined immunodeficiency (SCID). SCID disorders are split into groups based on their presence and/or functionality of B, T, and NK cells. Piglets from a line of Yorkshire pigs at Iowa State University were shown to be affected by T− B− NK+ SCID, representing the first example of naturally occurring SCID in pigs. Here, we present evidence for two spontaneous mutations as the molecular basis for this SCID phenotype. Flow cytometry analysis of thymocytes showed an increased frequency of immature T cells in SCID pigs. Fibroblasts from these pigs were more sensitive to ionizing radiation than non-SCID piglets, eliminating the RAG1 and RAG2 genes. Genetic and molecular analyses showed two mutations were present in the Artemis gene, which in homozygous or compound heterozygous state cause the immunodeficient phenotype. Rescue of SCID fibroblast radiosensitivity by human Artemis protein demonstrated that the identified Artemis mutations are the direct cause of this cellular phenotype. The work presented here reveals two mutations in the Artemis gene that cause T− B− NK+ SCID in pigs. The SCID pig can be an important biomedical model, but these mutations would be undesirable in commercial pig populations. The identified mutations and associated genetic tests can be used to address both of these issues. PMID:26320255

HIV and mental illness in Malawi and the neuropsychiatric sequelae of efavirenz.

PubMed

Drury, Andrew; Gleadow-Ware, Selena; Gilfillan, Sheila; Ahrens, Jen

2018-03-01

Little is published about mental disorders in Malawi, specifically in relation to Human Immunodeficiency Virus (HIV) and it's treatment. Efavirenz is a medication commonly used as part of triple therapy for HIV treatment. Indeed, in 2013, Malawi introduced 5A with Efavirenz as part of it's 1st line treatment for HIV. There exists some literature documenting known psychiatric side effects of Efavirenz, which include anxiety, mood changes, nightmares, psychosis and suicidal ideation. Little is known about what features are most common in the presentation and what factors in the patient and drug which may make this reaction more likely. The aim of this commentary is to review the association between HIV and psychiatric disorder, and consider the neuropsychiatric side-effects of Efavirenz. An evaluative literature review was completed by means of multiple electronic database search as well as an additional manual search to obtain published works identified through the electronic search. Search terms used were: Efavirenz, Acquired Immunodeficiency Syndrome, Africa, Antiretroviral Therapy, Developing Countries, Malawi, Mental Disorders, Public Health, and Psychiatry. This is an important area of study, as potentially large numbers of individuals with HIV are being placed on Efavirenz as first line treatment, yet 60% may experience some form of neuropsychiatric side effects.

The relationship between personality traits and AIDS in patients with human immunodeficiency virus.

PubMed

Salehi, Bahman; Zarinfar, Nader; Noori, Hasan

2016-06-01

This study carried out to survey the relationship between personality traits and Acquired Immunodeficiency Syndrome (AIDS) in patients with human immunodeficiency virus. This case-control study was conducted on 79 AIDS patients of Triangle Clinic in Arak (case group) and 80 healthy people of Valiasr Hospital in Arak (control group). Demographic information checklist and Cloninger' Temperament and Character inventory (TCI) were two instruments applied in the study. SPSS software V.19 and tests independent t-tests, Chi squared and Spearman correlation coefficient were used for data analysis with significant level of <0.05. The average of innovativeness variables (M:74.12), harm avoidance (M: 65.17), reward dependence (M:50.030), and self-directedness (M:35.02) in case group in comparison with control group was significantly higher, and there was a significant difference between two groups variables (P-0.000). The novelty seeking had the highest average in the AIDS patients with a history of addiction (M:74.00), and there was statistically significant difference between perseverance variable (P-0.021) and cooperativeness variable (P-0.041) in the two groups of AIDS patients. There was a significant relationship between novelty seeking and age at the onset of AIDS (P-0.038), harm avoidance and age at the onset of addiction (P-0.046), persistence and age at the onset of AIDS (P-0.035) and the time infected with HIV (P-0.033). It is found that two groups are different due to the personalities, so it is essential to consider the personality traits in order to prevent AIDS and also successfully treat patients suffering from AIDS. Copyright © 2016 Elsevier B.V. All rights reserved.

Psychiatric morbidity in asymptomatic human immunodeficiency virus patients.

PubMed

Chauhan, V S; Chaudhury, Suprakash; Sudarsanan, S; Srivastava, Kalpana

2013-07-01

Psychiatric morbidity in human immunodeficiency virus (HIV) patients is being studied all over the world. There is paucity of Indian literature particularly in asymptomatic HIV individuals. The aim of the following study is to establish the prevalence and the determinants of psychiatric morbidity in asymptomatic HIV patients. A cross-sectional study was undertaken to assess psychiatric morbidity as per ICD-10 dacryocystorhinostomy criteria in 100 consecutive asymptomatic seropositive HIV patients and an equal number of age, sex, education, economic and marital status matched HIV seronegative control. All subjects were assessed with the general health questionnaire (GHQ), mini mental status examination, hospital anxiety and depression scale (HADS) and sensation seeking scale (SSS) and the scores were analyzed statistically. Asymptomatic HIV positive patients had significantly higher GHQ caseness and depression but not anxiety on HADS as compared to HIV seronegative controls. On SSS asymptomatic HIV seropositive subjects showed significant higher scores in thrill and adventure seeking, experience seeking and boredom susceptibility as compared to controls. HIV seropositive patients had significantly higher incidence of total psychiatric morbidity. Among the individual disorders, alcohol dependence syndrome, sexual dysfunction and adjustment disorder were significantly increased compared with HIV seronegative controls. Psychiatric morbidity is higher in asymptomatic HIV patients when compared to HIV seronegative controls. Among the individual disorders, alcohol dependence syndrome, sexual dysfunction and adjustment disorder were significantly increased compared with HIV seronegative controls. High sensation seeking and substance abuse found in HIV seropositive patients may play a vital role in engaging in high-risk behavior resulting in this dreaded illness.

The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects.

PubMed

Brower, Kelly S; Del Vecchio, Michael T; Aronoff, Stephen C

2014-12-10

While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood. EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology. From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified. The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.

The Spectrum Disorders: An Exploratory Study of Family, Social, Individual and Psychological Distress Dimensions.

ERIC Educational Resources Information Center

Zarski, John J.; And Others

Although there is literature on Acquired Immune Deficiency Syndrome (AIDS), empirical research on family, social, and individual factors that may influence the psychological distress experienced by AIDS, Aids-Related Complex (ARC), Human Immunodeficiency Virus positive (HIV+) and worried well individuals is limited. This study explored the…

Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.

PubMed

McLaughlin, Lauren P; Bollard, Catherine M; Keller, Michael

2017-01-01

Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.

Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

PubMed Central

Carneiro-Sampaio, Magda; Coutinho, Antonio

2015-01-01

Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-α pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

No association between cumulative traumatic experiences and sex in risk for posttraumatic stress disorder among human immunodeficiency virus-positive adults.

PubMed

Morris, Tanya; Naidoo, Pamela; Cloete, Karen J; Harvey, Justin; Seedat, Soraya

2013-06-01

This study examined the association between the type and number of traumatic experiences and the conditional risk for posttraumatic stress disorder (PTSD), stratified by sex, in human immunodeficiency virus (HIV). We evaluated 465 (114 male and 350 female) HIV-positive adults attending HIV clinics in Cape Town, South Africa. Demographic and clinical data were collected, and the participants were screened for current PTSD and traumatic event exposure using the Mini-International Neuropsychiatric Interview and the Life Events Checklist, respectively. The highest attributable risk for PTSD was derived from sexual assault (17.4%) and transport accidents (16.9%). Only sexual assault was significantly (p = 0.002) associated with current PTSD. Although sex had no effect on the prediction of current PTSD, HIV-infected men tended to experience more lifetime traumas than HIV-infected women, with the men having significantly higher rates of exposure than women to physical assault (p = 0.018) and assault with a weapon (p = 0.001). These data highlight the importance of considering trauma type in contributing to the burden of PTSD in HIV-infected adults.

What has happened in the last 50 years in immunology.

PubMed

Wong, Melanie

2015-02-01

Fifty years ago, in 1964, our understanding of the immune system was very rudimentary. Gell and Coombs had just described classes of hypersensitivity reactions, and Bruton had described and commenced immunoglobulin replacement in agammaglobulinaemia. The distinction between T and B cells was not identified and characterised until the 1960s and 1970s. This was followed by increasing recognition of T and B cell collaboration in immune responses and identification of significant immunodeficiencies. CD4 and CD8 T cells were only recognised in the 1970s and 1980s. We now know of five CD4 subsets; dysfunction of each is associated with different disorders. By 2014, advances in technology have enabled identification of the genetic basis of over 240 primary immunodeficiencies. Research into the gut microbiome and vitamin D holds promise for the understanding, treatment and prevention of autoimmune and allergic diseases. Immunoglobulin preparations for the treatment of antibody deficiencies improved with the development of preparations for intravenous then subcutaneous administration, giving patients choice and the ability for home-based treatment, especially if experiencing infusion associated adverse effects. Newborn screening for severe combined immunodeficiency is a reality. Improvements in haemopoietic stem cell transplantation and now gene therapy, albeit still only available in the research setting, are improving long-term survival in primary immunodeficiencies. Biologic therapeutic agents are improving the control of autoimmune disease but potentially leading to secondary immunodeficiency, increasing the risk of opportunistic infection and malignancy. It is an exciting time. © 2015 The Author. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Human immunodeficiency virus endocrinopathy

PubMed Central

Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

2011-01-01

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. PMID:22028995

Use of Genetic Testing for Primary Immunodeficiency Patients.

PubMed

Heimall, Jennifer R; Hagin, David; Hajjar, Joud; Henrickson, Sarah E; Hernandez-Trujillo, Hillary S; Tan, Yuval; Kobrynski, Lisa; Paris, Kenneth; Torgerson, Troy R; Verbsky, James W; Wasserman, Richard L; Hsieh, Elena W Y; Blessing, Jack J; Chou, Janet S; Lawrence, Monica G; Marsh, Rebecca A; Rosenzweig, Sergio D; Orange, Jordan S; Abraham, Roshini S

2018-04-01

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS's recommendations for the use of genetic testing in light of these issues.

[Orofacial clinical manifestations in adult patients with variable common immunodeficiency].

PubMed

Chávez-García, Aurora Alejandra; Moreno-Alba, Miguel Ángel; Elizalde-Monroy, Martín; Segura-Méndez, Nora Hilda; Romero-Flores, Jovita; Cambray-Gutiérrez, Julio César; López-Pérez, Patricia; Del Rivero-Hernández, Leonel Gerardo

2015-01-01

Common variable immunodeficiency is the primary immunodeficiency (CVID) frequently found in adults. Its prevalence is estimated from 1:25,000 to 75,000 alive newborns; there are variations by ethnic groups, it is estimated about 50-70% in Caucasian patients. Oral cavity lesions are rarely found in adult patients with CVID, there are reports about lesions on pediatric patients mostly caused by infections. To describe the orofacial lesions (oral, maxillofacial and neck area) affecting adults with CVID. A transversal, prospective study was done in patients with CVID attended at Specialties Hospital, CMN SXXI, Mexico City. Patients where examined by the oral and maxillofacial surgeon and clinical findings were reported, then the descriptive analysis of the lesions was done. We evaluated 26 patients, 16 female and 10 males, average age of 38.6 years. In 18/26 patients we found oral lesions on 7 different types. The most frequent was minor salivary glands hiperplasia (19/26),petechiae (12/26) and herpetic ulcers (7/26). In head and neck, we found 4 different lesions, the most common was lymphadenopathy <2cm (4/26). The immunologic alterations associated to CVID favors the development of lesions mainly of infectious and probably autoinmune origin that affects the oral cavity and head and neck area.

Clinical and Immunological Features of Common Variable Immunodeficiency in China

PubMed Central

Lin, Lian-Jun; Wang, Yu-Chuan; Liu, Xin-Min

2015-01-01

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−/CD10+ 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. PMID:25635425

Relationship between Human Immunodeficiency Virus Neuroretinal Disorder and Vision-Specific Quality of Life among People with AIDS.

PubMed

Ashraf, Davin C; May, K Patrick; Holland, Gary N; Van Natta, Mark L; Wu, Albert W; Thorne, Jennifer E; Jabs, Douglas A

2015-12-01

Some human immunodeficiency virus (HIV)-infected individuals have evidence of optic nerve or retinal dysfunction that manifests as decreased contrast sensitivity, even with good best-corrected visual acuity (BCVA). This condition, termed HIV-related neuroretinal disorder (HIV-NRD), is a risk factor for vision impairment (BCVA <20/40), blindness (BCVA ≤20/200), and increased mortality. We investigated the effect of HIV-NRD on vision-specific quality of life (QOL). Cross-sectional analysis of data from a prospective, observational study. Individuals from the Longitudinal Study of the Ocular Complications of AIDS cohort who completed the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25), had BCVA of 20/40 or better, and had no evidence of ocular opportunistic infection or cataract. We compared QOL by HIV-NRD status, adjusting for potential confounding variables, using multiple linear regression. Among those with HIV-NRD, we assessed the relationship between VFQ-25 and the logarithm of contrast sensitivity (logCS), using Spearman correlation. We defined a minimum clinically important difference (MCID) as 1 standard error of measurement from a well-characterized, historical population of individuals with a variety of ophthalmic disorders. Subscales and composite VFQ-25 scores (0 = worst, 100 = best). A total of 813 individuals met study criteria. Those with HIV-NRD (n = 39 [4.8%]) had a lower mean composite score than those without HIV-NRD (81 vs. 89; P = 0.0002) and lower mean scores in the following subscales: near activities (77 vs. 86; P = 0.004), distance activities (85 vs. 91; P = 0.01), social functioning (89 vs. 96; P = 0.0005), mental health (75 vs. 87; P = 0.0001), dependency (81 vs. 94; P < 0.0001), driving (75 vs. 85; P = 0.02), color vision (90 vs. 97; P < 0.0001), and peripheral vision (85 vs. 91; P = 0.0496). Score differences for each of these subscales met criteria for MCID. Among those with HIV-NRD, there was a positive correlation between logCS and composite score (r = 0.36; 95% confidence interval, 0.04-0.60). HIV-NRD has a statistically significant and clinically meaningful association with decreased vision-specific QOL among people with AIDS and good BCVA. Published by Elsevier Inc.

The German national registry for primary immunodeficiencies (PID)

PubMed Central

Gathmann, B; Goldacker, S; Klima, M; Belohradsky, B H; Notheis, G; Ehl, S; Ritterbusch, H; Baumann, U; Meyer-Bahlburg, A; Witte, T; Schmidt, R; Borte, M; Borte, S; Linde, R; Schubert, R; Bienemann, K; Laws, H-J; Dueckers, G; Roesler, J; Rothoeft, T; Krüger, R; Scharbatke, E C; Masjosthusmann, K; Wasmuth, J-C; Moser, O; Kaiser, P; Groß-Wieltsch, U; Classen, C F; Horneff, G; Reiser, V; Binder, N; El-Helou, S M; Klein, C; Grimbacher, B; Kindle, G

2013-01-01

In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID. PMID:23607573

Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

PubMed

Yong, Pierre L; Orange, Jordan S; Sullivan, Kathleen E

2010-08-01

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

Seronegative celiac disease: Shedding light on an obscure clinical entity.

PubMed

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J; Ruggeri, Eugenio; Paterini, Paola; De Giorgio, Roberto

2016-09-01

Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency.

PubMed

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

2018-05-09

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.

Identification of ATM mutations using extended RT-PCR and restriction endonuclease fingerprinting, and elucidation of the repertoire of A-T mutations in Israel.

PubMed

Gilad, S; Khosravi, R; Harnik, R; Ziv, Y; Shkedy, D; Galanty, Y; Frydman, M; Levi, J; Sanal, O; Chessa, L; Smeets, D; Shiloh, Y; Bar-Shira, A

1998-01-01

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, and radiation sensitivity. The responsible gene, ATM, has an extensive genomic structure and encodes a large transcript with a 9.2 kb open reading frame (ORF). A-T mutations are extremely variable and most of them are private. We streamlined a high throughput protocol for the search for ATM mutations. The entire ATM ORF is amplified in a single RT-PCR step requiring a minimal amount of RNA. The product can serve for numerous nested PCRs in which overlapping portions of the ORF are further amplified and subjected to restriction endonuclease fingerprinting (REF) analysis. Splicing errors are readily detectable during the initial amplification of each portion. Using this protocol, we identified 5 novel A-T mutations and completed the elucidation of the molecular basis of A-T in the Israeli population.

N-acetylcysteine – passe-partout or much ado about nothing?

PubMed Central

Aitio, Mirja-Liisa

2006-01-01

In experimental studies, the old mucolytic agent N-acetylcysteine (NAC) has had beneficial effects in disorders supposedly linked to oxidative stress. Numerous, mainly small clinical trials with variable doses have yielded inconsistent results in a wide variety of diseases. NAC added to the conventional therapy of human immunodeficiency virus infection might be of benefit; in respect of chronic obstructive pulmonary disease, systematic reviews and meta-analyses suggested that prolonged treatment with NAC is efficacious, but a recent multicentre study has questioned this. In a large intervention trial on cancer recurrence, NAC was ineffective. NAC infusions have been widely used in acute hepatic failure but convincing evidence of its benefits is lacking. A preliminary study reported that NAC is effective in preventing radiocontrast-induced nephropathy but thereafter highly mixed results have been published, and even meta-analyses disagree on its efficacy. In intensive care NAC has mostly been a disappointment but recently it has ‘given promises’ in surgery with cardiopulmonary bypass. NAC therapy is routine only in paracetamol intoxication. PMID:16390346

Fibromyalgia in 300 adult index patients with primary immunodeficiency.

PubMed

Barton, James C; Bertoli, Luigi F; Barton, Jackson C; Acton, Ronald T

2017-01-01

We sought to determine the prevalence and clinical and laboratory associations of fibromyalgia in adults with primary immunodeficiency (immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable immunodeficiency (CVID). We performed a retrospective analysis of these observations in 300 non-Hispanic white adult index patients with recurrent/severe respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia; chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC); diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed univariate comparisons, logistic multivariable regressions, and an analysis of covariance. Mean age was 49 ± 12 (standard deviation) y. There were 246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjögren's syndrome, 8.0%; IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in patients with fibromyalgia. Logistic regression on fibromyalgia revealed three positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence interval 1.2, 5.6]); Sjögren's syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC (p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant interactions of chronic fatigue, Sjögren's syndrome, and interstitial cystitis on fibromyalgia. Fibromyalgia is common in non-Hispanic white adult index patients with primary immunodeficiency, especially women. Chronic fatigue, Sjögren's syndrome, and IC are significantly associated with fibromyalgia after adjustment for other independent variables.

Exclusion of Patients with a Severe T-Cell Defect Improves the Definition of Common Variable Immunodeficiency.

PubMed

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.

Immune Reconstitution Reactions in Human Immunodeficiency Virus–Negative Patients

PubMed Central

Scharschmidt, Tiffany C.; Amerson, Erin H.; Rosenberg, Oren S.; Jacobs, Richard A.; McCalmont, Timothy H.; Shinkai, Kanade

2013-01-01

Background Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon initially described in patients with human immunodeficiency virus. Upon initiation of combination antiretroviral therapy, recovery of cellular immunity triggers inflammation to a preexisting infection or antigen that causes paradoxical worsening of clinical disease. A similar phenomenon can occur in human immunodeficiency virus–negative patients, including pregnant women, neutropenic hosts, solidorgan or stem cell transplant recipients, and patients receiving tumor necrosis factor inhibitors. Observations We report a case of leprosy unmasking and downgrading reaction after stem cell transplantation that highlights some of the challenges inherent to the diagnosis of IRIS, especially in patients without human immunodeficiency virus infection, as well as review the spectrum of previously reported cases of IRIS reactions in this population. Conclusions The mechanism of immune reconstitution reactions is complex and variable, depending on the underlying antigen and the mechanism of immunosuppression or shift in immune status. Use of the term IRIS can aid our recognition of an important phenomenon that occurs in the setting of immunosuppression or shifts in immunity but should not deter us from thinking critically about the distinct processes that underlie this heterogeneous group of conditions. PMID:23324760

"Frontal systems" behaviors in comorbid human immunodeficiency virus infection and methamphetamine dependency.

PubMed

Marquine, María J; Iudicello, Jennifer E; Morgan, Erin E; Brown, Gregory G; Letendre, Scott L; Ellis, Ronald J; Deutsch, Reena; Woods, Steven Paul; Grant, Igor; Heaton, Robert K

2014-01-30

Human immunodeficiency virus (HIV) infection and methamphetamine (MA) dependence are associated with neural injury preferentially involving frontostriatal circuits. Little is known, however, about how these commonly comorbid conditions impact behavioral presentations typically associated with frontal systems dysfunction. Our sample comprised 47 HIV-uninfected/MA-nondependent; 25 HIV-uninfected/MA-dependent; 36 HIV-infected/MA-nondependent; and 28 HIV-infected/MA-dependent subjects. Participants completed self-report measures of "frontal systems" behaviors, including impulsivity/disinhibition, sensation-seeking, and apathy. They also underwent comprehensive neurocognitive and neuropsychiatric assessments that allowed for detailed characterization of neurocognitive deficits and comorbid/premorbid conditions, including lifetime Mood and Substance Use Disorders, Attention-Deficit/Hyperactivity Disorder, and Antisocial Personality Disorder. Multivariable regression models adjusting for potential confounds (i.e., demographics and comorbid/premorbid conditions) showed that MA dependence was independently associated with increased impulsivity/disinhibition, sensation-seeking and apathy, and HIV infection with greater apathy. However, we did not see synergistic/additive effects of HIV and MA on frontal systems behaviors. Global neurocognitive impairment was relatively independent of the frontal systems behaviors, which is consistent with the view that these constructs may have relatively separable biopsychosocial underpinnings. Future research should explore whether both neurocognitive impairment and frontal systems behaviors may independently contribute to everyday functioning outcomes relevant to HIV and MA. © 2013 Published by Elsevier Ireland Ltd.

Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.

PubMed

Belendiuk, Katherine A; Baldini, Lisa L; Bonn-Miller, Marcel O

2015-04-21

The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.

Therapeutic opportunities of small interfering RNA.

PubMed

Goyal, Bhoomika R; Patel, Mayur M; Soni, Mithil K; Bhadada, Shraddha V

2009-08-01

Formation of small interfering RNA (siRNA) occurs in two steps involving binding of the RNA nucleases to a large double-stranded RNA (dsRNA) and its cleavage into fragments called siRNA. In the second step, these siRNAs join a multinuclease complex, which degrades the homologous single-stranded mRNAs. The delivery of siRNA involves viral- and non-viral-mediated delivery systems; the approaches for chemical modifications have also been developed. It has various therapeutic applications for disorders like cardiovascular diseases, central nervous system (CNS) disorders, cancer, human immunodeficiency virus (HIV), hepatic disorders, etc. The present review gives an overview of the applications of siRNA and their potential for treating many hitherto untreatable diseases.

Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

PubMed

Rodà, Diana; Huici, Malka; Ricart, Sílvia; Vila, Jordi; Fortuny, Clàudia; Alsina, Laia

2017-02-01

Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

Restoring balance to B cells in ADA deficiency.

PubMed

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

Fatal EBV infection and variable clinical manifestations in an XLP-1 pedigree - rapid diagnosis of primary immunodeficiencies may save lives.

PubMed

Sperl, D; Benesch, M; Urban, C; Lackner, H; Sovinz, P; Speicher, M R; Uhrig, S; Schwarzbraun, T; Schwinger, W; zur Stadt, U; Beutel, K; Janka, G; Scarpatetti, M; Seidel, M G

2012-10-01

Two related boys who died from fulminant infectious mononucleosis were diagnosed with X-linked lymphoproliferative disease type 1 (XLP-1). Family screening (n=17) identified 6 female mutation carriers and 2 more XLP-1 patients in whom, despite recurrent infections, agammaglobulinemia, and Hodgkin's Disease, the genetic basis had been unknown; demonstrating that awareness and early genetic testing are crucial to reveal underlying primary immunodeficiencies and improve outcome. Furthermore, XLP should be included routinely in the differential diagnosis of severe hypogammaglobulinemia and/or lymphoma in males. © Georg Thieme Verlag KG Stuttgart · New York.

Primary immunodeficiency diseases in children: 15 year experience in a tertiary care medical center in Qatar.

PubMed

Ehlayel, Mohammad S; Bener, Abdulbari; Laban, Mohammad Abu

2013-02-01

Primary immunodeficiency diseases (PID) are a group of heterogeneous, rare, genetic, mainly childhood disorders that affect specific components of immune system leading to serious complications. This study is aimed at describing the prevalence and the categories of PID, the ages of onset and the diagnosis, the clinical presentations, the treatment modalities and the overall outcome of affected patients. A retrospective study was conducted on 131 pediatric patients (aged 0-14 years) diagnosed with PID at Hamad General Hospital during a 15-year period (1998-2012). Data of 131 patients (75 males & 56 females) was analyzed with an estimated prevalence of 4.7 PID patients per 100,000 children younger than 14 years of age. The most common type of PID was predominantly antibody deficiency (23.7 %), followed by other well-defined immunodeficiency syndromes (22.9 %), 19.1 % combined T and B cell immunodeficiency, but rare CVID, and no cases of complement deficiency. The mean onset age was 24.01 months and diagnosis age was 42.2 months. Recurrent infections, particularly pneumonia (48.9 %), failure to thrive (34.4 %), otitis media (26 %), sepsis (23.7 %), and chronic diarrhoea (21.4 %) were commonest presenting conditions. P. aeruginosa (15.7 %), Salmonella species (13.2 %), and Non-TB mycobacteria (13.2 %) were the most common bacterial isolates. The overall mortality rate was 21.4 % with combined immunodeficiency's accounting for 53.4 % of deaths. This study reveals that PIDs are not rare in children in Qatar; and like other studies predominantly antibody deficiencies are the most common. Strategies that reinforce awareness and education of practicing physicians, bone marrow transplantation, and establishing PID national registry should be adopted to reduce mortality and morbidity of PID patients in Qatar.

Surface immunoglobulins on blood lymphocytes of normal and immunodeficient persons studied by the mixed antiglobulin method

PubMed Central

Litwin, S. D.; Ochs, H.; Pollara, B.

1973-01-01

Surface immunoglobulins on human peripheral blood lymphocytes were investigated by the mixed antiglobulin technique—using the single layer mixed antiglobulin method as originally described (SLMA), and a modification employing a double layer of antibody (DLMA). Lymphocytes isolated from the blood of normal individuals had a mean of 7.8 and 18.4 per cent Ig + cells by the SLMA and DLMA techniques respectively. The DLMA data are similar to results obtained by other methods of detecting membrane Igs indicating that the mixed antiglobulin method is comparable in sensitivity. When the total numbers of Ig + cells, obtained by separate κ and λ testing, were compared with results obtained using single anti-light chain antisera, there was no significant difference, suggesting that most positive lymphocytes carry a single variety of light chain. Lymphocytes from the blood of seventeen patients with primary immunodeficiency were analysed. Four patients with variable immunodeficiency and four others with absent serum IgA all had normal surface Igs including α chains. All members of a family having an X-linked immunodeficiency had normal surface Igs including the affected members and a presumed carrier. Four cases of immunodeficiency associated with thymoma proved to have disparate findings. One patient exhibited a selective absence of μ antigens on the membranes of blood lymphocytes of over 2800 tested cells. Two other cases had normal surface Igs while a fourth patient, previously reported, lacked all surface Igs. PMID:4796276

Skin disorders affecting human immunodeficiency virus-infected children living in an orphanage in Ethiopia.

PubMed

Doni, S N; Mitchell, A L; Bogale, Y; Walker, S L

2012-01-01

Skin disorders are common in children in Ethiopia, and it is estimated that 92,000 Ethiopian children are infected with human immunodeficiency virus (HIV). HIV infection increases the prevalence of cutaneous disease, but the effect of antiretroviral therapy (ART) on the pattern of skin disease affecting children in sub-Saharan Africa (SSA) is unclear. To assess the prevalence and nature of skin disorders in HIV-infected children living in a dedicated orphanage in Addis Ababa, Ethiopia. Two dermatologists performed a clinical examination, including the skin, hair, nails and oral cavity of all the residents of an orphanage in Addis Ababa. The examiners knew that all the children were infected with HIV, but did not know their treatment or immune status. Diagnoses were made clinically and recorded anonymously, and treatment recommendations were made. Details of the children's treatment and CD4 lymphocyte counts were obtained after the examination had been completed. In total, 84 children [53 male (63%); 31 female (37%); median age 10 years] were examined. Of the 84 children, 57 (68%) were on ART, with 51 (61%) of these on cotrimoxazole prophylaxis. The median CD4 percentage was 27.1%. There were 66 children (79%) with at least one skin disorder; 21 of these had two disorders and 6 had three disorders. The commonest diagnosis was tinea capitis, affecting 39% of children. The other common diagnoses were: molluscum contagiosum (MC) (21%), verruca vulgaris (13%), plane warts (8%) and seborrhoeic dermatitis (7%). There was no significant difference in the prevalence of skin disease between children receiving ART and those who were not. Children with MC had significantly lower recent CD4 counts than children who did not have skin disease. Skin disorders in this population were very common, and the disorders identified were those that commonly affect children without HIV in Ethiopia. However, MC and plane warts appeared to have a higher frequency than would be expected in uninfected children. © The Author(s). CED © 2011 British Association of Dermatologists.

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

PubMed

Singh, Surjit; Gupta, Anju; Rawat, Amit

2013-01-08

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

Characteristics of 22q 11.2 deletion syndrome undiagnosed until adulthood: an example suggesting the importance of psychiatric manifestations

PubMed Central

Furuya, Kenta; Sasaki, Yosuke; Takeuchi, Taizo; Urita, Yoshihisa

2015-01-01

Patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit various combinations of signs and symptoms including facial dysmorphism, thymus absence, hypoparathyroidism, cellular immunodeficiency and cardiac abnormalities caused by microdeletion of chromosome 22q11.2. Most cases are diagnosed during post-natal cardiac evaluation, though some are diagnosed at later stages. We report the case of a 39-year-old man with 22q11.2DS presenting with seizure due to tardily manifested hypocalcaemia and anxiety disorder. Our experience suggests that 22q11.2DS patients lacking fatal or well-recognised manifestations such as cardiac defects, immunodeficiency and facial dysmorphism tend to survive without medical attention, and are therefore overlooked. Recognition of the age-related variance of the manifestations, and specifically of tardily manifested hypocalcaemia and psychiatric or developmental disorders as manifestations of 22q11.2DS in adulthood, is important for diagnosis and can also help us provide appropriate medical and psychosocial support for newly diagnosed 22q11.2DS patients in adolescence or adulthood and their families. PMID:26055589

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

ClinicalTrials.gov

2018-04-24

SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

Patterns of amino acid conservation in human and animal immunodeficiency viruses.

PubMed

Voitenko, Olga S; Dhroso, Andi; Feldmann, Anna; Korkin, Dmitry; Kalinina, Olga V

2016-09-01

Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity. We propose a method for identification of two types of surface residues clusters with abnormal conservation: extremely conserved and extremely variable clusters. We identify them on the surface of proteins from HIV and other animal immunodeficiency viruses. Both types of clusters are overrepresented on the interaction interfaces of viral proteins with other proteins, nucleic acids or low molecular-weight ligands, both in the viral particle and between the virus and its host. In the immunodeficiency viruses, the interaction interfaces are not more conserved than the corresponding proteins on an average, and we show that extremely conserved clusters coincide with protein-protein interaction hotspots, predicted as the residues with the largest energetic contribution to the interaction. Extremely variable clusters have been identified here for the first time. In the HIV-1 envelope protein gp120, they overlap with known antigenic sites. These antigenic sites also contain many residues from extremely conserved clusters, hence representing a unique interacting interface enriched both in extremely conserved and in extremely variable clusters of residues. This observation may have important implication for antiretroviral vaccine development. A Python package is available at https://bioinf.mpi-inf.mpg.de/publications/viral-ppi-pred/ voitenko@mpi-inf.mpg.de or kalinina@mpi-inf.mpg.de Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K Syndrome Type 1.

PubMed

Okano, Tsubasa; Imai, Kohsuke; Tsujita, Yuki; Mitsuiki, Noriko; Yoshida, Kenichi; Kamae, Chikako; Honma, Kenichi; Mitsui-Sekinaka, Kanako; Sekinaka, Yujin; Kato, Tamaki; Hanabusa, Katsuyuki; Endo, Eri; Takashima, Takehiro; Hiroki, Haruka; Yeh, Tzu-Wen; Tanaka, Keisuke; Nagahori, Masakazu; Tsuge, Ikuya; Bando, Yuki; Iwasaki, Fuminori; Shikama, Yoshiaki; Inoue, Masami; Kimoto, Tomiko; Moriguchi, Naohiko; Yuza, Yuki; Kaneko, Takashi; Suzuki, Kyoko; Matsubara, Tomoyo; Maruo, Yoshihiro; Kunitsu, Tomoaki; Waragai, Tomoko; Sano, Hideki; Hashimoto, Yuko; Tasaki, Kazuhiro; Suzuki, Osamu; Shirakawa, Toshihiko; Kato, Motohiro; Uchiyama, Toru; Ishimura, Masataka; Tauchi, Tetsuzo; Yagasaki, Hiroshi; Jou, Shiann-Tarng; Yu, Hsin-Hui; Kanegane, Hirokazu; Kracker, Sven; Durandy, Anne; Kojima, Daiei; Muramatsu, Hideki; Wada, Taizo; Inoue, Yuzaburo; Takada, Hidetoshi; Kojima, Seiji; Ogawa, Seishi; Ohara, Osamu; Nonoyama, Shigeaki; Morio, Tomohiro

2018-05-17

Activated phosphatidylinositol-3-OH kinase-delta (PI3Kδ) syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory infections, lymphoid hyperplasia, and herpesviridae infections due to germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) may be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, method, and outcomes of HSCT for APDS1 remain undefined. Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. We retrospectively reviewed the medical records of cohorts undergoing HSCT at collaborating facilities. Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence, and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced intensity conditioning (RIC). Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based RIC-HSCT ameliorated clinical symptoms, but transplant-related complications were frequent, including graft failure. Copyright © 2018. Published by Elsevier Inc.

Simian immunodeficiency viruses from African green monkeys display unusual genetic diversity.

PubMed Central

Johnson, P R; Fomsgaard, A; Allan, J; Gravell, M; London, W T; Olmsted, R A; Hirsch, V M

1990-01-01

African green monkeys are asymptomatic carriers of simian immunodeficiency viruses (SIV), commonly called SIVagm. As many as 50% of African green monkeys in the wild may be SIV seropositive. This high seroprevalence rate and the potential for genetic variation of lentiviruses suggested to us that African green monkeys may harbor widely differing genotypes of SIVagm. To investigate this hypothesis, we determined the entire nucleotide sequence of an infectious proviral molecular clone of SIVagm (155-4) and partial sequences (long terminal repeat and Gag) of three other distinct SIVagm isolates (90, gri-1, and ver-1). Comparisons among the SIVagm isolates revealed extreme diversity at the nucleotide and amino acid levels. Long terminal repeat nucleotide sequences varied up to 35% and Gag protein sequences varied up to 30%. The variability among SIVagm isolates exceeded the variability among any other group of primate lentiviruses. Our data suggest that SIVagm has been in the African green monkey population for a long time and may be the oldest primate lentivirus group in existence. PMID:2304139

Primary intestinal lymphangiectasia in an elderly female patient: A case report on a rare cause of secondary immunodeficiency.

PubMed

Huber, Xaver; Degen, Lukas; Muenst, Simone; Trendelenburg, Marten

2017-08-01

Protein loss via the gut can be caused by a number of gastrointestinal disorders, among which intestinal lymphangiectasia has been described to not only lead to a loss of proteins but also to a loss of lymphocytes, resembling secondary immunodeficiency. We are reporting on a 75-year-old female patient who came to our hospital because of a minor stroke. She had no history of serious infections. During the diagnostic work-up, we detected an apparent immunodeficiency syndrome associated with primary intestinal lymphangiectasia. Trying to characterize the alterations of the immune system, we not only found hypogammaglobulinemia and lymphopenia primarily affecting CD4+, and also CD8+ T cells, but also marked hypocomplementemia affecting levels of complement C4, C2, and C3. The loss of components of the immune system most likely was due to a chronic loss of immune cells and proteins via the intestinal lymphangiectasia, with levels of complement components following the pattern of protein electrophoresis. Thus, intestinal lymphangiectasia should not only be considered as a potential cause of secondary immune defects in an elderly patient, but can also be associated with additional hypocomplementemia.

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.

PubMed

Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael

2014-12-01

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.

The impact of human immunodeficiency virus-related diseases on pigmented skin types.

PubMed

Ameen, M

2013-10-01

Infection with human immunodeficiency virus (HIV) remains a significant problem globally. Early diagnosis and treatment with antiretroviral drugs has considerably improved health outcomes and decreased disease-related morbidity. HIV infection is associated with a wide range of skin disorders enabling dermatologists to diagnose HIV as well as associated opportunistic infections early in the course of disease. Despite concerted efforts by international health organizations to limit disease incidence, the prevalence of HIV infection remains high and is highest in sub-Saharan Africa. The diagnosis of HIV-related skin diseases is challenging as immunosuppression often results in atypical disease presentation. In addition, the clinical presentation will vary in pigmented skin types. The aim of this article is to describe disease variation in pigmented skin types. © 2013 The Author BJD © 2013 British Association of Dermatologists.

IgA vasculitis as a presentation of human immunodeficiency virus infection.

PubMed

Brandy-García, Anahy M; Santos-Juanes, Jorge; Suarez, Silvia; Caminal-Montero, Luis

2018-05-15

IgA vasculitis is a small-vessel vasculitis mediated by immune complexes. In clinical terms, it is characterized by palpable purpura in the lower limbs, joint involvement in the form of arthralgia or arthritis, and gastrointestinal and renal involvement (this will mark a poorer prognosis in adults). Infectious processes, mainly in the upper respiratory tract, are frequently found to be triggers. On the other hand, human immunodeficiency virus (HIV) causes immune dysfunction, which triggers hypergammaglobulinemia and can trigger autoimmune disorders. At times, this can affect the vascular endothelium, giving rise to vasculitic manifestations, although there are few reports in the literature of its role in the presentation of HIV. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease.

PubMed

Uhlig, Holm H

2013-12-01

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, has multifactorial aetiology with complex interactions between genetic and environmental factors. Over 150 genetic loci are associated with IBD. The genetic contribution of the majority of those loci towards explained heritability is low. Recent studies have reported an increasing spectrum of human monogenic diseases that can present with IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset of intestinal inflammation. The 40 monogenic defects with IBD-like pathology selected in this review can be grouped into defects in intestinal epithelial barrier and stress response, immunodeficiencies affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders as well as defects with disturbed T and B lymphocyte selection and activation. In addition, there are defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signalling. Related to the variable penetrance of the IBD-like phenotype, there is a likely role for modifier genes and gene-environment interactions. Treatment options in this heterogeneous group of disorders range from anti-inflammatory and immunosuppressive therapy to blockade of tumour necrosis factor α and IL-1β, surgery, haematopoietic stem cell transplantation or gene therapy. Understanding of prototypic monogenic 'orphan' diseases cannot only provide treatment options for the affected patients but also inform on immunological mechanisms and complement the functional understanding of the pathogenesis of IBD.

Common Variable Immunodeficiency Caused by FANC Mutations.

PubMed

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

2017-07-01

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.

Cytokine polymorphisms are associated with poor sleep maintenance in adults living with human immunodeficiency virus/acquired immunodeficiency syndrome.

PubMed

Lee, Kathryn A; Gay, Caryl; Pullinger, Clive R; Hennessy, Mary Dawn; Zak, Rochelle S; Aouizerat, Bradley E

2014-03-01

Cytokine activity and polymorphisms have been associated with sleep outcomes in prior animal and human research. The purpose of this study was to determine whether circulating plasma cytokines and cytokine polymorphisms are associated with the poor sleep maintenance commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Cross-sectional descriptive study. HIV clinics and community sites in the San Francisco Bay area. A convenience sample of 289 adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS. None. A wrist actigraph was worn for 72 h to estimate the percentage of wake after sleep onset (WASO%) and total sleep time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for demographic variables such as race and sex, and clinical variables such as CD4+ count and medications, higher WASO% was associated with single nucleotide polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also associated with short sleep duration. This study strengthens the evidence for an association between inflammation and sleep maintenance problems. In this chronic illness population, cytokine polymorphisms associated with wake after sleep onset provide direction for intervention research aimed at comparing anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance and total sleep time.

[Study of quality of life in adults with common variable immunodeficiency by using the Questionnaire SF-36].

PubMed

López-Pérez, Patricia; Miranda-Novales, Guadalupe; Segura-Méndez, Nora Hilda; Del Rivero-Hernández, Leonel; Cambray-Gutiérrez, Cesar; Chávez-García, Aurora

2014-01-01

Quality of life is a multidimensional concept that includes physical, emotional and social components associated with the disease. The use of tools to assess the Quality of Life Health Related (HRQOL) has increased in recent decades. Common variable immunodeficiency (CVID) is the most commonly diagnosed primary immunodeficiency. To evaluate the quality of life in patients with CVID using the questionnaire SF -36. A descriptive cross-sectional survey included 23 patients diagnosed with CVID, belonging to the Immunodeficiency Clinic Service of Allergology and Clinical Immunology in CMN Siglo XXI, IMSS. The questionnaire SF- 36 validated in Spanish was applied. descriptive statistics with simple frequencies and percentages, inferential statistics: Fisher exact test and ANOVA to compare means. The study involved 23 patients, 14 women (60%) and 9 men (40%), mean age 38.6 ± 14.7 years. The highest score was obtained in 83% emotional role. Dimensions with further deterioration in both genders were: 54% general health, vitality 59% and physical performance 72%. No differences were found regarding gender. The only issue in which statistically significant differences were found in patients with more than 3 comorbidities was change in health status in the past year (p=0.007). Patients with severe comorbidities, such as haematologicaloncological (leukemias, lymphomas, neoplasms), and pulmonary (severe bronchiectasis) showed further deterioration in the aspects of physical performance 73% and 64% emotional role. 65% of patients reported an improvement in health status in 74% in the last year. Adult patients with CVID show deterioration in different dimensions, particularly in the areas of general health, vitality and physical performance. Patients with severe comorbidities such as leukemia, lymphomas, malignancies and severe bronchiectasis show further deterioration in some aspects of quality of life, especially in physical performance and emotional role. A higher number of comorbidities was significantly associated with a lower score in changing health. The questionnaire SF-36 is useful for evaluating the quality of life of our patients with CVID.

[Graves disease and IgA deficiency as manifestations of 22q11.2 deletion syndrome].

PubMed

Silva, João Miguel de Almeida; Silva, Cecília Pereira; Melo, Flavio Fernando Nogueira de; Silva, Luis Alberto A; Utagawa, Claudia Yamada

2010-08-01

The 22q11.2 deletion syndrome (22q11.2DS) is related to a high phenotypic variability including the velocardiofacial/DiGeorge spectrum. Autoimmune, endocrine and immunodeficiency manifestations have been reportedly associated with the syndrome. The objective of this study was to report a case of 22q11.2DS associated with IgA deficiency and Graves disease and review literature in order to verify the frequency of syndrome alterations. Autoimmune disorders have been increasingly related to 22q11.2DS, and new phenotypes are being incorporated in the clinical spectrum of this syndrome. In our study we found that Graves disease in association with 22q11.2DS was reported in only sixteen patients, and fifteen cases were described in the last 13 years. Based on the incidence and on the amplitude of this recognized spectrum, we reinforce the findings of literature that Graves disease should be included on the 22q11.2DS manifestations, which would lead us to seek it with 22q11.2 deletion patients.

Immunological considerations in in utero hematopoetic stem cell transplantation (IUHCT)

PubMed Central

Loewendorf, Andrea I.; Csete, Marie; Flake, Alan

2014-01-01

In utero hematopoietic stem cell transplantation (IUHCT) is an attractive approach and a potentially curative surgery for several congenital hematopoietic diseases. In practice, this application has succeeded only in the context of Severe Combined Immunodeficiency Disorders. Here, we review potential immunological hurdles for the long-term establishment of chimerism and discuss relevant models and findings from both postnatal hematopoietic stem cell transplantation and IUHCT. PMID:25610396

Unusual multiple large abscesses of the liver: interest of the radiological features and the real-time PCR to distinguish between bacterial and amebic etiologies.

PubMed

Desoubeaux, Guillaume; Chaussade, Hélène; Thellier, Marc; Poussing, Sophie; Bastides, Frédéric; Bailly, Eric; Lanotte, Philippe; Alison, Daniel; Brunereau, Laurent; Bernard, Louis; Chandenier, Jacques

2014-01-01

We report a rare case of amebiasis generating 19 large liver abscesses. Such a quantity of abscesses is rare, especially when occurring in a young casual traveler without any immunodeficiency disorders. A possible co-infection was excluded. By contrast, the amebic etiology was confirmed by means of serology and real-time PCR.

Orbital Epstein-Barr Virus-Positive Polymorphic B-Cell Lymphoproliferative Disorder in an Apparently Immunocompetent Woman.

PubMed

Abendroth, Michael D; Bayerl, Michael G; Wilkinson, Michael J; Claxton, David F; Specht, Charles S

2017-12-01

We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old, apparently immunocompetent woman. She presented with a chief complaint of orbital swelling and tenderness and was found to have a lesion involving the right lacrimal gland and distal superior and lateral rectus muscles. Histology of the lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and scattered cells that resembled the Reed-Sternberg (R-S) cells of classical Hodgkin lymphoma. The R-S-like cells were positive for PAX5 and CD30 and negative for CD15, supporting a diagnosis of polymorphic B-cell LPD. In situ hybridization for EBV-encoded RNA demonstrated the presence of EBV. Most EBV-positive polymorphic B-cell LPDs are associated with immunodeficiency. However, the patient described is HIV-negative and has no identifiable defects in immunoglobulin levels or cell-mediated immunity. This raises the question of whether she has an underlying immunodeficiency resulting from subtle changes in T-cell physiology, or whether chronic EBV infection contributed to her immune dysfunction through an unclear mechanism. The orbital mass partially regressed with chemotherapy, and the patient has done well clinically with no recurrence of this EBV-LPD for over 2 years.

The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines

PubMed Central

Palios, John; Kadoglou, Nikolaos P. E.; Lampropoulos, Stylianos

2012-01-01

Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, lipids, and arterial blood pressure abnormalities, leading to extensive atherogenic arterial wall changes. Nevertheless, the above traditional cardiovascular risk factors merely explain the exacerbated cardiovascular risk in MS. Nowadays, the adipose-tissue derivatives, known as adipokines, have been suggested to contribute to chronic inflammation and the MS-related cardiovascular disease. In view of a novel understanding on how adipokines affect the pathogenesis of HIV/HAART-related MS and cardiovascular complications, this paper focuses on the interaction of the metabolic pathways and the potential cardiovascular consequences. Based on the current literature, we suggest adipokines to have a role in the pathogenesis of the HIV/HAART-related MS. It is crucial to understand the pathophysiology of the HIV/HAART-related MS and apply therapeutic strategies in order to reduce cardiovascular risk in HIV patients. PMID:22203832

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

PubMed Central

Lee, Pamela P.; Lau, Yu-Lung

2017-01-01

The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions. PMID:28702025

Treatment of Infants Identified by Newborn Screening for Severe Combined Immunodeficiency

PubMed Central

Dorsey, Morna J.; Dvorak, Christopher C.; Cowan, Morton J.; Puck, Jennifer M.

2017-01-01

Background Severe combined immunodeficiency (SCID) is characterized by severely impaired T cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pre-transplant care and transplant protocols for NBS identified SCID infants, as well as for infants with other T lymphopenic disorders detected by NBS. Methods We developed approaches to management based on the study of infants identified by SCID NBS who received care at UCSF. Results From August 2010 through October 2016, 32 NBS SCID and leaky SCID cases from California and other states were treated and 42 NBS identified non-SCID T cell lymphopenia (TCL) cases were followed. Conclusions Our center’s approach supports successful outcomes; systematic review of our practice provides a framework for diagnosis and management, recognizing that more data will continue to shape best practices. PMID:28270365

Human Immune Disorder Arising from Mutation of the α Chain of the Interleukin-2 Receptor

NASA Astrophysics Data System (ADS)

Sharfe, Nigel; Dadi, Harjit K.; Shahar, Michal; Roifman, Chaim M.

1997-04-01

Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the interleukin-2 receptor α chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin 2. This immunodeficiency is characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B cell development. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1, and furthermore they fail to normally down-regulate levels of the anti-apoptotic protein bcl-2.

Primary Immunodeficiencies: “New” Disease in an Old Country

PubMed Central

Lee, Pamela P W; Lau, Yu-Lung

2009-01-01

Primary immunodeficiency disorders (PIDs) are rare inborn errors of the immune system. Patients with PIDs are unique models that exemplify the functional and phenotypic consequences of various immune defects underlying infections, autoimmunity, lymphoproliferation, allergy and cancer. Over 150 PID syndromes were characterized in the past 60 years, with an ever growing list of new entities being discovered. Because of their rarity, multi-center collaboration for pooled data analysis and molecular studies is important to gain meaningful insights into the phenotypic and genetic diversities of PIDs. In this article, we summarize our research findings on PIDs in Chinese population in the past 20 years. Close collaboration among various immunology centers, cross-referrals and systematic data analysis constitute the foundation for research on PIDs. Future directions include establishment of a national PID registry, raising awareness of PIDs and securing sufficient resources for patient care and scientific research. PMID:20003815

Ophthalmologic Disease in HIV Infection: Recent Changes in Pathophysiology and Treatment.

PubMed

Stewart, Michael W

2017-10-19

Ophthalmologic conditions were among the earliest described findings in patients with the acquired immunodeficiency syndrome (AIDS). The purpose of this review is to highlight recent changes in the pathophysiology and management of ophthalmologic conditions in patients infected with the human immunodeficiency virus (HIV). The introduction of highly active antiretroviral therapy (HAART) in 1996 changed ophthalmologic findings from predominantly acute infectious diseases to chronic, slowly progressive, debilitating conditions. HIV-associated neuroretinal disorder infrequently leads to blindness, but it causes visual disability in a large percentage of patients. Cytomegalovirus retinitis is now seen less commonly in the USA, but it remains an important cause of blindness in HIV-infected patients from developing countries. Immune recovery uveitis has emerged as a major cause of visual disability in the USA. As HIV has become a chronic disease, visual disability due to chronic noninfectious diseases have become increasingly important.

New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

PubMed

Ollague Sierra, Jose E; Ollague Torres, Jose M

2013-04-01

Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by an Intracellular Anti-Rev Single-Chain Antibody

NASA Astrophysics Data System (ADS)

Duan, Lingxun; Bagasra, Omar; Laughlin, Mark A.; Oakes, Joseph W.; Pomerantz, Roger J.

1994-05-01

Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of an anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.

Amyloidosis in association with spontaneous feline immunodeficiency virus infection.

PubMed

Asproni, Pietro; Abramo, Francesca; Millanta, Francesca; Lorenzi, Davide; Poli, Alessandro

2013-04-01

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.

In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS)

PubMed Central

1994-01-01

Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus- induced immune disorders with similar immunopathogenic mechanisms. PMID:7964495

Extreme Growth Failure is a Common Presentation of Ligase IV Deficiency

PubMed Central

Murray, Jennie E; Bicknell, Louise S; Yigit, Gökhan; Duker, Angela L; van Kogelenberg, Margriet; Haghayegh, Sara; Wieczorek, Dagmar; Kayserili, Hülya; Albert, Michael H; Wise, Carol A; Brandon, January; Kleefstra, Tjitske; Warris, Adilia; van der Flier, Michiel; Bamforth, J Steven; Doonanco, Kurston; Adès, Lesley; Ma, Alan; Field, Michael; Johnson, Diana; Shackley, Fiona; Firth, Helen; Woods, C Geoffrey; Nürnberg, Peter; Gatti, Richard A; Hurles, Matthew; Bober, Michael B; Wollnik, Bernd; Jackson, Andrew P

2014-01-01

Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC −10.1 s.d., height −5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype–phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder. PMID:24123394

Epidemiology of diabetes mellitus and associated cardiovascular risk factors: focus on human immunodeficiency virus and psychiatric disorders.

PubMed

Zimmet, Paul

2005-04-01

Type 2 diabetes mellitus and obesity have reached epidemic proportions in many developing and developed nations, leading to talk of the "twin epidemics." The latest projections from the International Diabetes Federation suggest that 190 million people worldwide currently have type 2 diabetes. In addition, > or = 300 million people worldwide have impaired glucose tolerance (IGT). These statistics represent an epidemic of major proportions--possibly the largest epidemic in human history--in terms of glucose intolerance and cardiovascular disease (CVD) risk because individuals with IGT are at substantially higher risk for diabetes and CVD than are members of the general population. Along with IGT, the metabolic syndrome comprises other major CVD risk factors, including insulin resistance, central obesity, and dyslipidemia; insulin resistance has been implicated as the single most common cause of the syndrome. Although the exact prevalence of the metabolic syndrome is unknown, the syndrome is widespread among adults in developed nations, becoming more prevalent with age. Epidemiologic data suggest that in patients with schizophrenia or affective disorders, both diabetes and obesity are 1.5 to 2.0 times more prevalent than in the general population. Furthermore, because adverse effects of certain therapies for human immunodeficiency virus (HIV) infection and psychiatric disorders increase the risk for developing diabetes, obesity, and the metabolic syndrome, such therapies should be carefully chosen, particularly considering CVD risk. Appropriate therapy may be determined via screening of patients for levels of fasting blood glucose and lipids, as well as other CVD risk factors, before initiating use of second-generation antipsychotic agents or highly active antiretroviral therapy.

The Hematopoietic Stem Cell Therapy for Exploration of Space

NASA Technical Reports Server (NTRS)

Roach, Allana Nicole; Brezo, Jelena

2002-01-01

Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse

PubMed Central

Kiebala, Michelle; Singh, Meera V.; Piepenbrink, Michael S.; Qiu, Xing; Kobie, James J.; Maggirwar, Sanjay B.

2015-01-01

Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB) inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK) activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders. PMID:26076359

Virology, Immunology, and Clinical Course of HIV Infection.

ERIC Educational Resources Information Center

McCutchan, J. Allen

1990-01-01

Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

PubMed

Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

2017-10-05

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

A novel de novo activating mutation in STAT3 identified in a patient with common variable immunodeficiency (CVID).

PubMed

Russell, Mark A; Pigors, Manuela; Houssen, Maha E; Manson, Ania; Kelsell, David; Longhurst, Hilary; Morgan, Noel G

2018-02-01

Common variable immunodeficiency (CVID) is characterised by repeated infection associated with primary acquired hypogammaglobulinemia. CVID frequently has a complex aetiology but, in certain cases, it has a monogenic cause. Recently, variants within the gene encoding the transcription factor STAT3 were implicated in monogenic CVID. Here, we describe a patient presenting with symptoms synonymous with CVID, who displayed reduced levels of IgG and IgA, repeated viral infections and multiple additional co-morbidities. Whole-exome sequencing revealed a de novo novel missense mutation in the coiled-coil domain of STAT3 (c.870A>T; p.K290N). Accordingly, the K290N variant of STAT3 was generated, and a STAT3 responsive dual-luciferase reporter assay revealed that the variant strongly enhances STAT3 transcriptional activity both under basal and stimulated (with IL-6) conditions. Overall, these data complement earlier studies in which CVID-associated STAT3 mutations are predicted to enhance transcriptional activity, suggesting that such patients may respond favourably to IL-6 receptor antagonists (e.g. tocilizumab). Copyright © 2017 Elsevier Inc. All rights reserved.

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency

PubMed Central

Maglione, Paul J.; Cols, Montserrat

2018-01-01

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches. PMID:28983810

The Risk of Mental Health Disorders Among U.S. Military Personnel Infected with Human Immunodeficiency Virus, Active Component, U.S. Armed Forces, 2000-2011

DTIC Science & Technology

2012-05-01

Defense Medical Surveillance System (DMSS). An incident case of HSV2 was defi ned as two or more medical encounters with a diagnosis of “ genital ... herpes ” (ICD-9-CM 054.1 with any fi ft h digit) in any diagnostic position. Incidence rates of MHD were com- pared between three groups of active com

Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

PubMed

Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

2011-07-18

The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of neural networks to model complex immunogenetic associations of disease: human leukocyte antigen impact on the progression of human immunodeficiency virus infection.

PubMed

Ioannidis, J P; McQueen, P G; Goedert, J J; Kaslow, R A

1998-03-01

Complex immunogenetic associations of disease involving a large number of gene products are difficult to evaluate with traditional statistical methods and may require complex modeling. The authors evaluated the performance of feed-forward backpropagation neural networks in predicting rapid progression to acquired immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus (HIV) infection on the basis of major histocompatibility complex variables. Networks were trained on data from patients from the Multicenter AIDS Cohort Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102). The outcome of interest was rapid disease progression, defined as progression to AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables were selected as network inputs with multivariate regression and a previously described algorithm selecting markers with extreme point estimates for progression risk. Network performance was compared with that of logistic regression. Networks with 15 HLA inputs and a single hidden layer of five nodes achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs. 77.0% and 76.9%, respectively, achieved by logistic regression. When validated on the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of 74.3%, vs. 53.1% and 61.4%, respectively, for logistic regression. Neural networks offer further support to the notion that HIV disease progression may be dependent on complex interactions between different class I and class II alleles and transporters associated with antigen processing variants. The effect in the current models is of moderate magnitude, and more data as well as other host and pathogen variables may need to be considered to improve the performance of the models. Artificial intelligence methods may complement linear statistical methods for evaluating immunogenetic associations of disease.

Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

PubMed

Sperlich, Johannes M; Grimbacher, Bodo; Workman, Sarita; Haque, Tanzina; Seneviratne, Suranjith L; Burns, Siobhan O; Reiser, Veronika; Vach, Werner; Hurst, John R; Lowe, David M

Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated. To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations. We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID. There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%. Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Human Immunodeficiency Virus Disease Severity, Psychiatric Symptoms, and Functional Outcomes in Perinatally Infected Youth

PubMed Central

Nachman, Sharon; Chernoff, Miriam; Williams, Paige; Hodge, Janice; Heston, Jerry; Gadow, Kenneth D.

2012-01-01

Objective To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Design Cross-sectional analysis of entry data from an observational, prospective 2-year study. Logistic and linear regression models adjusted for potential confounders were used. Setting Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Participants Youth aged 6 to 17 years who had HIV infection (N=319). Main Exposures Antiretroviral treatment and perinatal HIV infection. Main Outcome Measures Youth and primary care-givers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social, and academic functioning; and quality of life. Results Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms, older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms, higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage at study entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms. A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Conclusion Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic, and social functioning, all of which warrant additional study. Trial Registration clinicaltrials.gov Identifier: NCT00100542 PMID:22312169

Herpes simplex encephalitis (HSE) and the immunocompromised: a clinical and autopsy study of HSE in the settings of cancer and human immunodeficiency virus-type 1 infection.

PubMed

Schiff, D; Rosenblum, M K

1998-03-01

Although herpes simplex encephalitis (HSE) is not regarded as an opportunistic infection, the occurrence of HSE in immunocompromised patients has been documented and the suggestion made that unusual clinical and neuropathologic features characterize the disorder in this population. To further characterize HSE as it affects the immunodeficient, the authors reviewed the clinical and pathological findings in three immunocompromised patients with autopsy-proven HSE. Two patients had cancer (one with lymphoma and another with glioblastoma multiforme), one was known to be human immunodeficiency virus-type 1 (HIV-1)-seropositive and a second was suspected of harboring underlying HIV-1 infection. Two were receiving dexamethasone at onset of HSE. All had fever, mental status changes and new, focal neurological deficits or worsening of established deficits. Cerebrospinal fluid (CSF) pleocytosis was absent or minimal and head computerized tomographic (CT) scans, performed in all cases, were unrevealing. No patient was clinically suspected of having HSE, only one received acyclovir (for concurrent mucocutaneous herpes) and HSE played a major role in all deaths. Autopsy revealed an unusual form of HSE characterized by a noninflammatory, pseudoischemic histological presentation and the unexpected persistence of viral antigens in abundance despite survival beyond the clinical stage during which inflammatory responses usually peak and productive brain infection wanes. The incidence of HSE in the immunocompromised may be underestimated. Preexistent neurological disease, a noninflammatory CSF profile and negative CT scan may confound the diagnosis in this population, a typical clinical presentation notwithstanding. Increased clinical suspicion, the use of magnetic resonance imaging and polymerase chain reaction analysis of CSF for herpes simplex virus nucleic acid sequences may permit more rapid diagnosis and treatment. The absence of inflammatory infiltrates in some fatal cases of HSE suggests that an intact immune response is not requisite to the devastating neurological injury characteristic of this disorder.

An Aptamer That Neutralizes R5 Strains of Human Immunodeficiency Virus Type 1 Blocks gp120-CCR5 Interaction

PubMed Central

Dey, Antu K.; Khati, Makobetsa; Tang, Min; Wyatt, Richard; Lea, Susan M.; James, William

2005-01-01

We recently described the isolation and structural characterization of 2′-fluoropyrimidine-substituted RNA aptamers that bind to gp120 of R5 strains of human immunodeficiency virus type 1 and thereby potently neutralize the infectivity of phylogenetically diverse R5 strains. Here we investigate the physical basis of their antiviral action. We show that both N-linked oligosaccharides and the variable loops V1/V2 and V3 are not required for binding of one aptamer, B40, to gp120. Using surface plasmon resonance binding analyses, we show that the aptamer binds to the CCR5-binding site on gp120 in a relatively CD4-independent manner, providing a mechanistic explanation for its neutralizing potency. PMID:16227301

Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a case-control study.

PubMed

Gelenske, Thais; e Farias, Francisco Alfredo Bandeira; de Alencar Ximenes, Ricardo Arraes; de Melo, Heloísa Ramos Lacerda; de Albuquerque, Maria de Fátima Pessoa Militão; de Carvalho, Erico Higino; de Medeiros Barros, Zoraya; Diniz, George Tadeu Nunes; Filho, Demócrito de Barros Miranda

2010-06-01

Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

DTIC Science & Technology

2012-01-01

including; Alzheimer’s disease (Mac- cioni et al. 2009), Parkinson’s disease (Hirsch and Hunot 2009), spinal cord injury (Chan 2008), multiple sclerosis ...states such as multiple sclerosis (Kraus et al. 2000), human immunodeficiency virus dementia (Fischer- Smith et al. 2001), and meningitis (Cauwels et al...Immunologic mechanisms of multiple sclerosis . Neuroi- maging Clin. N. Am. 18, 577–588. Gaylord K. M. (2006) The psychosocial effects of combat: the frequently

Neuropsychological performance in patients with asymptomatic HIV-1 infection.

PubMed

Martínez-Banfi, Martha; Vélez, Jorge I; Perea, M Victoria; García, Ricardo; Puentes-Rozo, Pedro J; Mebarak Chams, Moises; Ladera, Valentina

2018-05-01

Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

Recombinant interleukin 2 therapy in severe combined immunodeficiency disease.

PubMed Central

Pahwa, R; Chatila, T; Pahwa, S; Paradise, C; Day, N K; Geha, R; Schwartz, S A; Slade, H; Oyaizu, N; Good, R A

1989-01-01

Severe combined immunodeficiency disease (SCID) is a congenital disorder of severe B- and T-lymphocyte dysfunction in which several pathogenic mechanisms have been identified. The present study describes a female child with SCID who had a primary defect in the ability of T cells to secrete interleukin 2 (IL-2). B- and T-cell numbers were normal, but their functions were severely deficient. Mitogen and antigen-driven lymphoproliferative responses were diminished but were correctable in vitro with recombinant IL-2 (rIL-2). The patient's phytohemagglutinin-stimulated lymphocytes expressed IL-2 receptors normally. Despite the presence of the gene for IL-2, the patient's cells were grossly deficient in messenger RNA for IL-2 and endogenous IL-2 production. Pokeweed mitogen-driven B-cell differentiation was decreased and was not corrected by the addition of normal T cells to the B cells. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed. Therapy with rIL-2 (30,000 units/kg, given daily i.v.) resulted in marked clinical improvement as well in improved T-cell functions. The child, now 3 yr old, has been on rIL-2 therapy for 2 yr and receives rIL-2 (30,000 units/kg) three times weekly at home. This case study points to a new direction in the treatment of such disorders with rIL-2. Images PMID:2787027

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using Unbiased Network Clustering in Large Electronic Datasets.

PubMed

Farmer, Jocelyn R; Ong, Mei-Sing; Barmettler, Sara; Yonker, Lael M; Fuleihan, Ramsay; Sullivan, Kathleen E; Cunningham-Rundles, Charlotte; Walter, Jolan E

2017-01-01

Common variable immunodeficiency (CVID) is increasingly recognized for its association with autoimmune and inflammatory complications. Despite recent advances in immunophenotypic and genetic discovery, clinical care of CVID remains limited by our inability to accurately model risk for non-infectious disease development. Herein, we demonstrate the utility of unbiased network clustering as a novel method to analyze inter-relationships between non-infectious disease outcomes in CVID using databases at the United States Immunodeficiency Network (USIDNET), the centralized immunodeficiency registry of the United States, and Partners, a tertiary care network in Boston, MA, USA, with a shared electronic medical record amenable to natural language processing. Immunophenotypes were comparable in terms of native antibody deficiencies, low titer response to pneumococcus, and B cell maturation arrest. However, recorded non-infectious disease outcomes were more substantial in the Partners cohort across the spectrum of lymphoproliferation, cytopenias, autoimmunity, atopy, and malignancy. Using unbiased network clustering to analyze 34 non-infectious disease outcomes in the Partners cohort, we further identified unique patterns of lymphoproliferative (two clusters), autoimmune (two clusters), and atopic (one cluster) disease that were defined as CVID non-infectious endotypes according to discrete and non-overlapping immunophenotypes. Markers were both previously described {high serum IgE in the atopic cluster [odds ratio (OR) 6.5] and low class-switched memory B cells in the total lymphoproliferative cluster (OR 9.2)} and novel [low serum C3 in the total lymphoproliferative cluster (OR 5.1)]. Mortality risk in the Partners cohort was significantly associated with individual non-infectious disease outcomes as well as lymphoproliferative cluster 2, specifically (OR 5.9). In contrast, unbiased network clustering failed to associate known comorbidities in the adult USIDNET cohort. Together, these data suggest that unbiased network clustering can be used in CVID to redefine non-infectious disease inter-relationships; however, applicability may be limited to datasets well annotated through mechanisms such as natural language processing. The lymphoproliferative, autoimmune, and atopic Partners CVID endotypes herein described can be used moving forward to streamline genetic and biomarker discovery and to facilitate early screening and intervention in CVID patients at highest risk for autoimmune and inflammatory progression.

[Pneumocystis Pneumonia in 107 HIV Infected Patients Admitted to the Department of Infectious Diseases at Santa Maria Hospital, Lisbon (2002 - 2013)].

PubMed

Grilo, Vilma; Pereira, Aida

2016-10-01

Pneumocystis jirovecii pneumonia remains one of the most common opportunistic illnesses in patients infected with the human immunodeficiency virus. It is currently the most reported AIDS-defining infection in Portugal. The aims of this study were to analyze the features of a human immunodeficiency virus /Pneumocystis jirovecii pneumonia coinfected population, to compare it with the current literature, and to evaluate comparatively subpopulations of patients based on the previous knowledge of the human immunodeficiency virus infection, Pneumocystis jirovecii pneumonia diagnostic method and discharge results. A retrospective, observational, non-controlled study was conducted. The 107 patients admitted to the Department of Infectious Diseases at Santa Maria Hospital, in Lisbon, between the 1st of January 2002 and the 31st of December 2013, that presented the simultaneous diagnosis of human immunodeficiency virus infection and Pneumocystis jirovecii pneumonia were included. We studied epidemiologic and clinical data collected from the patient files, including immunity status, human immunodeficiency virus viral load and treatment options. The variables were analyzed using the Chi-Squared and Mann-Whitney tests. Data from this population evidenced male predominance (81.3%), patient age between 20 - 39 years old in 59.2% and heterossexual human immunodeficiency virus transmission in 48.6%; 24.3% were immigrants. Human immunodeficiency virus infection was previously known in 62.6% patients, but 76.2% were not engaged in medical care. A TCD4+ cell count ≤ 200 cells/mm3, high viral load and oropharyngeal candidiasis (72%) were prevalent risk factors associated with the Pneumocystis jirovecii pneumonia infection; hypoxaemia (78.5%) and LDH (82.2%), which are markers of Pneumocystis jirovecii pneumonia severity, did not translate into a worse prognosis. Pneumocystis jirovecii was only identified in 55.1% patients, pointing out the hardship involved in achieving a definite diagnosis. The inicial drug of choice was TMP-SMX (91.6%), and corticosteroid adjuvant therapy was added in 75.7%. The in-hospital mortality was 13.1%. The comparative analysis between groups of patients showed that injection drug users knew more frequently their human immunodeficiency virus seropositivity before the current hospitalization, which could be explained by the presence of specific programs aiming the early human immunodeficiency virus diagnosis in this population. However, there is lack of adhesion to the treatment and follow up consultations, putting them at a higher risk of Pneumocystis jirovecii pneumonia infection and other AIDS related diseases. Besides showing the classic Pneumocystis jirovecii pneumonia presentation, healthcare seeking was delayed, especially amongst patients with newly diagnosed human immunodeficiency virus infection. Moreover, the Pneumocystis jirovecii pneumonia diagnosis was difficult to obtain, mainly because of the current limitations of Pneumocystis jirovecii pneumonia diagnostic techniques, the simultaneous presence of other respiratory diseases, and the need of a high degree of clinical suspicion. This population of human immunodeficiency virus and Pneumocystis jirovecii pneumonia coinfected patients shows similarities with the data from previous studies, particularly considering Portuguese epidemiological data. The main differences found were the Pneumocystis jirovecii pneumonia diagnostic frequence in injection drug users, the importance of previous/recurrent episodes of Pneumocystis jirovecii pneumonia as a risk factor and the frequency of concurrent pulmonary diseases. The deceased patients showed less imagiologic features suggestive of Pneumocystis jirovecii pneumonia, and advanced age was found to be an indicative of worst prognosis.

Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

PubMed

De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

2014-10-01

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. © The Author(s) 2014.

Predictors of unsafe sexual behavior among people living with human immunodeficiency virus/AIDS attending antiretroviral therapy center in Western India.

PubMed

Mehta, Kedar G; Baxi, Rajendra; Chavda, Parag; Patel, Sangita; Mazumdar, Vihang

2016-01-01

As more and more people with human immunodeficiency virus (HIV) live longer and healthier lives because of antiretroviral therapy (ART), an increasing number of sexual transmissions of HIV may arise from these people living with HIV/AIDS (PLWHA). Hence, this study is conducted to assess the predictors of unsafe sexual behavior among PLWHA on ART in Western India. The current cross-sectional study was carried out among 175 PLWHAs attending ART center of a Tertiary Care Hospital in Western India. Unsafe sex was defined as inconsistent and/or incorrect condom use. A total of 39 variables from four domains viz., sociodemographic, relationship-related, medical and psycho-social factors were studied for their relationship to unsafe sexual behavior. The variables found to be significantly associated with unsafe sex practices in bivariate analysis were explored by multivariate analysis using multiple logistic regression in SPSS 17.0 version. Fifty-eight percentage of PLWHAs were practicing unsafe sex. 15 out of total 39 variables showed significant association in bivariate analysis. Finally, 11 of them showed significant association in multivariate analysis. Young age group, illiteracy, lack of counseling, misbeliefs about condom use, nondisclosure to spouse and lack of partner communication were the major factors found to be independently associated with unsafe sex in multivariate analysis. Appropriate interventions like need-based counseling are required to address risk factors associated with unsafe sex.

Effect of Highly Active Antiretroviral Therapy on Incident AIDS Using Calendar Period as an Instrumental Variable

PubMed Central

Cole, Stephen R.; Greenland, Sander; Brown, Todd T.; Chmiel, Joan S.; Kingsley, Lawrence; Detels, Roger

2009-01-01

Human immunodeficiency virus (HIV) researchers often use calendar periods as an imperfect proxy for highly active antiretroviral therapy (HAART) when estimating the effect of HAART on HIV disease progression. The authors report on 614 HIV-positive homosexual men followed from 1984 to 2007 in 4 US cities. During 5,321 person-years, 268 of 614 men incurred acquired immunodeficiency syndrome, 49 died, and 90 were lost to follow-up. Comparing the pre-HAART calendar period (<1996) with the HAART calendar period (≥1996) resulted in a naive rate ratio of 3.62 (95% confidence limits: 2.67, 4.92). However, this estimate is likely biased because of misclassification of HAART use by calendar period. Simple calendar period approaches may circumvent confounding by indication at the cost of inducing exposure misclassification. To correct this misclassification, the authors propose an instrumental-variable estimator analogous to ones previously used for noncompliance corrections in randomized clinical trials. When the pre-HAART calendar period was compared with the HAART calendar period, the instrumental-variable rate ratio was 5.02 (95% confidence limits: 3.45, 7.31), 39% higher than the naive result. Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence. PMID:19318615

Advances in Basic and Clinical Immunology 2009

PubMed Central

Chinen, Javier; Shearer, William T.

2010-01-01

In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

Correlation between Lymphocyte CD4 Count, Treatment Duration, Opportunistic Infection and Cognitive Function in Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS) Patients.

PubMed

Fitri, Fasihah Irfani; Rambe, Aldy Safruddin; Fitri, Aida

2018-04-15

Human immunodeficiency virus (HIV) infection is an epidemic worldwide, despite the marked benefits of antiretroviral therapy (ARV) in reducing severe HIV-associated dementia. A milder form of neurocognitive disorders are still prevalent and remain a challenge. This study aimed to determine the correlation between plasma cluster of differentiation 4 (CD4) lymphocyte, duration of ARV treatment, opportunistic infections, and cognitive function in HIV-AIDS patients. A cross-sectional study involving 85 HIV-AIDS patients was conducted at Adam Malik General Hospital Medan, Indonesia. All subjects were subjected to physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts. Out of the 85 subjects evaluated, the proportion concerning sexes include 52 males (61.2 %) and 33 females (38.8%). The mean age was 38.53 ± 9.77 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r = 0.271, p = 0.012), but there was no significant correlation between duration of ARV treatment and MoCA-INA score. There was also no difference in MoCA-INA score based on the presence of opportunistic infection. Lymphocyte CD4 count was independently correlated with cognitive function in HIV-AIDS patients.

A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

PubMed Central

Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

2016-01-01

Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

Repetitive sequences based on genotyping of Candida albicans isolates obtained from Iranian patients with human immunodeficiency virus

PubMed Central

Tamai, Iradj Ashrafi; Salehi, Taghi Zahraei; Sharifzadeh, Aghil; Shokri, Hojjatollah; Khosravi, Ali Reza

2014-01-01

Objective(s): Candidiasis infection caused by Candida albicans has been known as a major problem in patients with immune disorders. The objective of this study was to genotype the C. albicans isolates obtained from oral cavity of patients with positive human immunodeficiency virus (HIV+) with or/and without oropharyngeal candidiasis (OPC). Materials and Methods: A total of 100 C. albicans isolates from Iranian HIV+patients were genotyped using specific PCR primers of the 25S rDNA and RPS genes. Results: The frequencies of genotypes A, B and C which were achieved using 25S rDNA , were 66, 24 and 10 percent, respectively. In addition, genotypes D and E were not found in this study. Each C. albicans genotype was further classified into four subtypes (types 2, 3, 2/3 and 3/4) by PCR amplification targeting RPS sequence. Conclusion: In general, genotype A3 constituted the majority of understudy clinical isolates obtained from oral cavity of Iranian HIV+ patients. PMID:25691923

Allogenic fetal liver cells have a distinct competitive engraftment advantage over adult bone marrow cells when infused into fetal as compared with adult severe combined immunodeficient recipients.

PubMed

Taylor, Patricia A; McElmurry, Ronald T; Lees, Christopher J; Harrison, David E; Blazar, Bruce R

2002-03-01

In utero transplantation (IUT) is becoming a viable option for the treatment of various immune and metabolic disorders diagnosed early in gestation. In this study, donor fetal liver cells had a 10-fold competitive engraftment advantage relative to adult bone marrow in allogeneic fetal severe combined immunodeficient (SCID) recipients compared with adult recipients. In contrast, adult bone marrow cells engrafted slightly better than fetal liver cells in allogeneic adult SCID transplant recipients. By using different ratios of fetal and adult cell mixtures, fetal liver cells repopulated 8.2 times better than adult bone marrow cells in fetal recipients, but only 0.8 times as well in adult recipients. Fetal SCID recipients were more permissive to an allogeneic donor graft than adult recipients. These data indicate that the recipient microenvironment may regulate the engraftment efficiency of a given stem cell source and suggest that the use of cord blood should be tested in clinical IUT.

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.

Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.

PubMed

Tuijnenburg, Paul; Lango Allen, Hana; Burns, Siobhan O; Greene, Daniel; Jansen, Machiel H; Staples, Emily; Stephens, Jonathan; Carss, Keren J; Biasci, Daniele; Baxendale, Helen; Thomas, Moira; Chandra, Anita; Kiani-Alikhan, Sorena; Longhurst, Hilary J; Seneviratne, Suranjith L; Oksenhendler, Eric; Simeoni, Ilenia; de Bree, Godelieve J; Tool, Anton T J; van Leeuwen, Ester M M; Ebberink, Eduard H T M; Meijer, Alexander B; Tuna, Salih; Whitehorn, Deborah; Brown, Matthew; Turro, Ernest; Thrasher, Adrian J; Smith, Kenneth G C; Thaventhiran, James E; Kuijpers, Taco W

2018-03-02

The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort. In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21 low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity

PubMed Central

Dendrou, Calliope A.; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G.; Attfield, Kathrine E.; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A.; Desel, Christiane; Faergeman, Soren L.; Cheeseman, Jane; Neville, Matt J.; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R.; Everett, Christine; Bell, John I.; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2017-01-01

Thousands of genetic variants have been identified that contribute to the development of complex diseases, but determining how to fully elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders, subsequent molecular, cellular, in vivo and structural functional follow-up and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for multiple autoimmune disorders. PMID:27807284

The fatigue experience for women with human immunodeficiency virus.

PubMed

Lee, K A; Portillo, C J; Miramontes, H

1999-01-01

To examine fatigue as a symptom experienced by women with human immunodeficiency virus (HIV). A convenience sample of 100 women with HIV. Independent sample t-tests were used to test for mean differences in fatigue related to variables in the women's sociocultural and home environment (ethnicity, employment, marital status, and parenting). Pearson product moment correlations were used to examine significant relationships between fatigue and physiologic variables (age, CD4 cell count, and sleep). Lower CD4 cell counts were related to more daytime sleep, higher evening fatigue, and higher morning fatigue. Morning fatigue was related to duration of wake episodes during the night, napping, and perception of sleep disturbance during the past week. The number of awakenings during the first night predicted the severity of fatigue the next evening. To understand the fatigue experienced by women with HIV, researchers and clinicians must focus on the relative contributions of sociocultural, home, and physiologic environments within which these women live. Additional research is ongoing to identify the strategies these women use to manage daily activities such that gender-relevant and culturally relevant interventions for alleviating fatigue can be tested in women with a variety of chronic illnesses, including HIV and acquired immune deficiency syndrome.

Phylogenetic analysis of feline immunodeficiency virus strains from naturally infected cats in Belgium and The Netherlands.

PubMed

Roukaerts, Inge D M; Theuns, Sebastiaan; Taffin, Elien R L; Daminet, Sylvie; Nauwynck, Hans J

2015-01-22

Feline immunodeficiency virus (FIV) is a major pathogen in feline populations worldwide, with seroprevalences up to 26%. Virus strains circulating in domestic cats are subdivided into different phylogenetic clades (A-E), based on the genetic diversity of the V3-V4 region of the env gene. In this report, a phylogenetic analysis of the V3-V4 env region, and a variable region in the gag gene was made for 36 FIV strains isolated in Belgium and The Netherlands. All newly generated gag sequences clustered together with previously known clade A FIV viruses, confirming the dominance of clade A viruses in Northern Europe. The same was true for the obtained env sequences, with only one sample of an unknown env subtype. Overall, the genetic diversity of FIV strains sequenced in this report was low. This indicates a relatively recent introduction of FIV in Belgium and The Netherlands. However, the sample with an unknown env subtype indicates that new introductions of FIV from unknown origin do occur and this will likely increase genetic variability in time. Copyright © 2014 Elsevier B.V. All rights reserved.

Predictors of sexual risk behaviors among adolescent mothers in a human immunodeficiency virus prevention program.

PubMed

Koniak-Griffin, Deborah; Stein, Judith A

2006-03-01

The purpose of this study was to determine the following: (1) whether adolescent mothers in a human immunodeficiency virus (HIV) prevention program had significantly greater perceived self-efficacy and perceived behavioral control to use condoms, and more favorable outcome expectancies and subjective norms regarding condom use than those in a health education control group, 3 months after intervention; and (2) the impact of the 3-month postintervention theoretical variables on intentions to use condoms at 3 months and sexual risk behaviors at 6 months. Structural equation modeling with latent variables was used to assess the influence of theoretical variables and treatment condition using data from 496 participants (78% Latinas, 18% African-Americans) who completed questionnaires at baseline and at 3- and 6-month follow-up evaluations. Substantial improvements were shown by both groups, with a slight advantage for the HIV prevention group, on all theoretical variables between pretest and the follow-up evaluations. In the predictive model, the intervention group reported significantly fewer sex partners. By using intentions to use condoms as a mediator, greater self-efficacy, hedonistic beliefs, positive subjective norms, and less unprotected sex predicted intentions to use condoms, which, in turn, predicted less unprotected sex. Lower subjective norms modestly predicted multiple partners. Significant indirect paths mediated through intentions to use condoms were observed. These data support a relationship among several constructs from social cognitive theory and the theory of reasoned action, and subsequent sexual risk behaviors. HIV-prevention programs for adolescent mothers should be designed to include these theoretical constructs and to address contextual factors influencing their lives.

A Randomized Controlled Trial of a Resilience-Based Intervention for Children Affected by Parental HIV: Educational Outcomes at 24-, 30-, and 36-Months

ERIC Educational Resources Information Center

Harrison, Sayward E.; Li, Xiaoming; Zhang, JiaJia; Zhao, Junfeng; Zhao, Guoxiang

2018-01-01

Children of parents with human immunodeficiency virus (HIV) are at-risk for a variety of negative outcomes, including poor educational achievement. The multi-level, resilience-based "ChildCARE" intervention has been found to yield short-term improvement in a number of school-related variables for children affected by parental HIV.…

Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.

PubMed

Sazzad, Hossain M S; Rainey, Jeanette J; Kahn, Anna-Lea; Mach, Ondrej; Liyanage, Jayantha B L; Alam, Ahmed Nawsher; Kawser, Choudhury A; Hossain, Asgar; Sutter, Roland; Luby, Stephen P

2014-11-01

Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion. Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD. From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative. The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunodeficiencies

PubMed Central

Ballow, M; Notarangelo, L; Grimbacher, B; Cunningham-Rundles, C; Stein, M; Helbert, M; Gathmann, B; Kindle, G; Knight, A K; Ochs, H D; Sullivan, K; Franco, J L

2009-01-01

Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented. PMID:19883420

Altered White Matter Integrity in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: A Tract-Based Spatial Statistics Study.

PubMed

Oh, Se Won; Shin, Na-Young; Choi, Jun Yong; Lee, Seung-Koo; Bang, Mi Rim

2018-01-01

Human immunodeficiency virus (HIV) infection has been known to damage the microstructural integrity of white matter (WM). However, only a few studies have assessed the brain regions in HIV-associated neurocognitive disorders (HAND) with diffusion tensor imaging (DTI). Therefore, we sought to compare the DTI data between HIV patients with and without HAND using tract-based spatial statistics (TBSS). Twenty-two HIV-infected patients (10 with HAND and 12 without HAND) and 11 healthy controls (HC) were enrolled in this study. A whole-brain analysis of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was performed with TBSS and a subsequent 20 tract-specific region-of-interest (ROI)-based analysis to localize and compare altered WM integrity in all group contrasts. Compared with HC, patients with HAND showed decreased FA in the right frontoparietal WM including the upper corticospinal tract (CST) and increased MD and RD in the bilateral frontoparietal WM, corpus callosum, bilateral CSTs and bilateral cerebellar peduncles. The DTI values did not significantly differ between HIV patients with and without HAND or between HIV patients without HAND and HC. In the ROI-based analysis, decreased FA was observed in the right superior longitudinal fasciculus and was significantly correlated with decreased information processing speed, memory, executive function, and fine motor function in HIV patients. These results suggest that altered integrity of the frontoparietal WM contributes to cognitive dysfunction in HIV patients.

Medical management of adult transsexual persons.

PubMed

Knezevich, Emily L; Viereck, Laura K; Drincic, Andjela T

2012-01-01

Gender identity disorder (GID), or transsexualism, is an increasingly recognized medical condition with an expanding body of medical literature to support the use of established therapeutic guidelines. Transsexualism can be effectively managed through exogenous cross-sex hormone administration used to induce development of desired sex characteristics, as well as use of other agents, such as aldosterone antagonists, aimed at decreasing physical characteristics of the undesired sex. Many complications can arise with the use of the available therapies, and these must be considered before determining the appropriate course of action. This review describes methods, including both pharmacotherapy and surgical interventions, for effective medical management of both male and female adults with GID. In addition, specific goals of therapy as well as safety aspects with long-term use of pharmacotherapeutic agents are discussed. This review also discusses some special considerations for treating patients with significant, yet common, comorbid diseases such as human immunodeficiency virus infection, acquired immunodeficiency syndrome, and viral hepatitis, as these conditions may complicate the clinical course and preclude some patients from using certain therapies. Pharmacist involvement in the management of transsexualism can be extremely beneficial to patients and other health care providers. Pharmacists can help determine the appropriate therapy, optimize dosages, monitor for adverse effects, and educate patients on what to expect during their therapy. Pharmacists should become knowledgeable about guidelines and current literature on transsexualism, understand the monitoring parameters for safe and effective therapy, and establish themselves as partners in the collaborative management of this disorder. © 2012, Pharmacotherapy Publications, Inc.

Vaccination with a feline immunodeficiency virus multiepitopic peptide induces cell-mediated and humoral immune responses in cats, but does not confer protection.

PubMed Central

Flynn, J N; Cannon, C A; Neil, J C; Jarrett, O

1997-01-01

Cats were immunized with a 46-residue multiepitopic synthetic peptide of feline immunodeficiency virus (FIV) comprising immunodominant epitopes present in the third variable domain of the envelope glycoprotein, transmembrane glycoprotein (TM), and p24 Gag core protein, using Quil A as an adjuvant. All vaccinated cats developed a humoral response which recognized the synthetic peptide immunogen and the intact viral core and envelope proteins. A FIV Gag- and Env-specific effector cytotoxic T-lymphocyte response was also detected in the peripheral blood of vaccinated cats, which peaked at week 30. This response appeared to be major histocompatibility complex restricted. Epitope mapping studies revealed that both the cellular and humoral immune responses were directed principally to a peptide within the TM glycoprotein, CNQNQFFCK. However, vaccination did not confer protection when cats were challenged with the Petaluma isolate of FIV at week 35. PMID:9311839

Phenotype Variation in Human Immunodeficiency virus Type 1 Transmission and Disease Progression

PubMed Central

Cavarelli, Mariangela; Scarlatti, Gabriella

2009-01-01

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. PMID:19893208

Phenotype variation in human immunodeficiency virus type 1 transmission and disease progression.

PubMed

Cavarelli, Mariangela; Scarlatti, Gabriella

2009-01-01

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.

Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient.

PubMed

Bernal-Cano, F; Joseph, J T; Koralnik, I J

2007-10-01

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.

Promoting Cardiovascular Health in Patients Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

PubMed

Harris, Robin

2018-03-01

Patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (PLWHA) are at increased risk of cardiovascular disease because of advances in human immunodeficiency virus/acquired immunodeficiency syndrome treatment and increased life expectancy. Cardiovascular health promotion in PLWHA includes strategies for risk factor reduction, disease prevention, early detection, and treatment of cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

PubMed

Dendrou, Calliope A; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G; Attfield, Kathrine E; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A; Desel, Christiane; Faergeman, Soren L; Cheeseman, Jane; Neville, Matt J; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R; Everett, Christine; Bell, John I; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2016-11-02

Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders. Copyright © 2016, American Association for the Advancement of Science.

DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis

PubMed Central

Starokadomskyy, Petro; Gemelli, Terry; Rios, Jonathan J.; Xing, Chao; Wang, Richard C.; Li, Haiying; Pokatayev, Vladislav; Dozmorov, Igor; Khan, Shaheen; Miyata, Naoteru; Fraile, Guadalupe; Raj, Prithvi; Xu, Zhe; Xu, Zigang; Ma, Lin; Lin, Zhimiao; Wang, Huijun; Yang, Yong; Ben-Amitai, Dan; Orenstein, Naama; Mussaffi, Huda; Baselga, Eulalia; Tadini, Gianluca; Grunebaum, Eyal; Sarajlija, Adrijan; Krzewski, Konrad; Wakeland, Edward K.; Yan, Nan; de la Morena, Maria Teresa; Zinn, Andrew R.; Burstein, Ezra

2016-01-01

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts expression of POLA1, the gene encoding the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency results in increased type I interferon production. This enzyme is necessary for RNA:DNA primer synthesis during DNA replication and strikingly, POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Altogether, this work identified POLA1 as a critical regulator of the type I interferon response. PMID:27019227

Targeting methionine cycle as a potential therapeutic strategy for immune disorders.

PubMed

Li, Heng; Lu, Huimin; Tang, Wei; Zuo, Jianping

2017-08-23

Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.

Risk of sexual transmitted infection following bipolar disorder: a nationwide population-based cohort study.

PubMed

Lee, Shyh-Chyang; Hu, Chang-Kuo; Hung, Jeng-Hsiu; Yang, Albert C; Tsai, Shih-Jen; Huang, Min-Wei; Hu, Li-Yu; Shen, Cheng-Che

2018-04-03

Bipolar disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous studies have investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial. We explored the association between bipolar disorder and the subsequent development of STIs, including human immunodeficiency virus infection; primary, secondary, and latent syphilis; genital warts; gonorrhea; chlamydial infection; and trichomoniasis. The bipolar cohort consisted of 1293 patients, and the comparison cohort consisted of 5172 matched control subjects without bipolar disorder. The incidence of subsequent STIs (hazard ratio (HR) = 2.23, 95% confidence interval (CI) 1.68-2.96) was higher among the patients with bipolar disorder than in the comparison cohort. Furthermore, female gender is a risk factor for acquisition of STIs (HR = 2.36, 95% CI 1.73-4.89) among patients with bipolar disorder. For individual STIs, the results indicated that the patients with bipolar disorder exhibited a markedly higher risk for subsequently contracting syphilis, genital warts, and trichomoniasis. Bipolar disorder might increase the risk of subsequent newly diagnosed STIs, including syphilis, genital warts, and trichomoniasis. Clinicians should pay particular attention to STIs in patients with bipolar disorder. Patients with bipolar disorder, especially those with a history of high-risk sexual behaviors, should be routinely screened for STIs. We identified patients who were diagnosed with bipolar disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without bipolar disorder who were matched with the bipolar cohort according to age and gender. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.

Rapid molecular diagnostics of severe primary immunodeficiency determined by using targeted next-generation sequencing.

PubMed

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

2016-10-01

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 (<20× read depth) or high sequence homology (pseudogenes) are complemented by amplicon-based sequencing with specific primers to ensure 100% coverage of all targeted regions. Analysis of 20 patient samples with low T-cell receptor excision circle numbers on newborn screening or a positive family history or clinical suspicion of SCID or other severe PIDD identified deleterious mutations in 14 of them. Identified pathogenic variants included both single nucleotide variants and exonic copy number variants, such as hemizygous nonsense, frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM, RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous nonsense mutation in CHD7. High-throughput deep sequencing analysis with complete clinical validation greatly increases the 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.

Natural Variation of Drug Susceptibility in Wild-Type Human Immunodeficiency Virus Type 1

PubMed Central

Parkin, N. T.; Hellmann, N. S.; Whitcomb, J. M.; Kiss, L.; Chappey, C.; Petropoulos, C. J.

2004-01-01

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,” for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs. PMID:14742192

The European internet-based patient and research database for primary immunodeficiencies: update 2011

PubMed Central

Gathmann, B; Binder, N; Ehl, S; Kindle, G

2012-01-01

In order to build a common data pool and estimate the disease burden of primary immunodeficiencies (PID) in Europe, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Since its start in 2004, 13 708 patients from 41 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity with 2880 patients or 21% of all entries, followed by selective immunoglobulin A (sIgA) deficiency (1424 patients, 10·4%). The total documented prevalence of PID is highest in France, with five patients per 100 000 inhabitants. The highest documented prevalence for a single disease is 1·3 per 100 000 inhabitants for sIgA deficiency in Hungary. The highest reported incidence of PID per 100 000 live births was 16·2 for the period 1999–2002 in France. The highest reported incidence rate for a single disease was 6·7 for sIgA deficiency in Spain for the period 1999–2002. The genetic cause was known in 36·2% of all registered patients. Consanguinity was reported in 8·8%, and 18·5% of patients were reported to be familial cases; 27·9% of patients were diagnosed after the age of 16. We did not observe a significant decrease in the diagnostic delay for most diseases between 1987 and 2010. The most frequently reported long-term medication is immunoglobulin replacement. PMID:22288591

Presentation and outcome amongst older Singaporeans living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): does age alone drive excess mortality?

PubMed

Huggan, Paul J; Foo, Rui Min; Olszyna, Dariusz; Chew, Nicholas S; Smitasen, Nares; Mukhopadhyay, Amartya; Archuleta, Sophia

2012-12-01

There is little detailed information on human immunodeficiency virus (HIV) amongst older adults in Singapore. A retrospective study of 121 consecutive referrals of patients presenting for HIV care was conducted. Demographic, clinical and laboratory variables were collected. A prognostic model derived from the North American Veterans' Affairs Cohort Study (VACS) was used to estimate prognosis. The median age at presentation was 43 (range, 18 to 76). Thirty-eight patients (31%) were aged 50 or older and 106 patients (88%) were male. Older patients were more likely to be of Chinese ethnicity (P = 0.035), married (P = 0.0001), unemployed or retired (P = 0.0001), and to have acquired their infection heterosexually (P = 0.0002). The majority of patients in both groups were symptomatic at presentation. Eighty-one (67%) had CD4 counts less than 200 at baseline with no observable differences in HIV ribonucleic acid (RNA) or clinical stage based on age. Non-Acquired Immunodeficiency Syndrome (AIDS) morbidity was observed more frequently amongst older patients. The estimated prognosis of patients differed significantly based on age. Using the VACS Index and comparing younger patients with those aged 50 and above, mean 5 year mortality estimates were 25% and 50% respectively (P <0.001). A trend towards earlier antiretroviral therapy was noted amongst older patients (P = 0.067) driven mainly by fewer financial difficulties reported as barriers to treatment. Older patients form a high proportion of newly diagnosed HIV/AIDS cases and present with more non-AIDS morbidity. This confers a poor prognosis despite comparable findings with younger patients in terms of clinical stage, AIDS-defining illness, CD4 count and HIV viral load.

Changes in thyroid function in Ethiopian and non-Ethiopian Israeli patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome.

PubMed

Cahn, Avivit; Chairsky-Segal, Irena; Olshtain-Pops, Keren; Maayan, Sholomo; Wolf, Dana; Dresner-Pollak, Rivka

2012-01-01

To investigate whether human immunodeficiency virus (HIV) infection or its treatment is a risk factor for thyroid dysfunction and whether thyroid function changes over time in 2 distinct subpopulations with HIV or acquired immunodeficiency syndrome (AIDS) in Israel: Ethiopian immigrants and Israeli patients. Serum thyroid-stimulating hormone (TSH) and free thyroxine levels were determined in HIV carriers undergoing follow-up at the Hadassah-Hebrew University Medical Center HIV clinic in Jerusalem, Israel, and these thyroid measurements were correlated with clinical and laboratory variables pertaining to their disease, including disease duration, drug therapy, viral load, CD4 count, low-density lipoprotein cholesterol, and creatine kinase. Serum samples stored at -20°C from the time of referral were tested as well. We recruited 121 consecutive patients with HIV or AIDS for this study: 60 Ethiopians and 61 Israeli patients. Of the 121 patients, 4 (3%) had abnormal thyroid function-subclinical hypothyroidism in 2, overt hypothyroidism in 1, and overt hyperthyroidism in 1. Previously stored serum samples were available for 60 of the 121 patients and revealed 2 additional patients with subclinical hypothyroidism, whose TSH has normalized in the subsequent test. Throughout the follow-up period of 3.2 ± 1.9 years, the mean TSH level remained unchanged in the Israeli cohort but significantly declined in the Ethiopian cohort. Thyroid function abnormalities were uncommon in these Israeli patients with HIV or AIDS. This finding does not support the need for routine thyroid function tests in this patient population. The decline in TSH level in the Ethiopian population over time probably represents a shift from an iodine-deficient to an iodine-sufficient country.

Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

PubMed Central

Scarlatti, G; Leitner, T; Halapi, E; Wahlberg, J; Marchisio, P; Clerici-Schoeller, M A; Wigzell, H; Fenyö, E M; Albert, J; Uhlén, M

1993-01-01

We have compared the variable region 3 sequences from 10 human immunodeficiency virus type 1 (HIV-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA of cultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission. PMID:8446584

Space-time Considerations for Hematopoietic Stem Cell Transplantation

PubMed Central

Bhattacharya, Deepta; Ehrlich, Lauren I. Richie; Weissman, Irving L.

2009-01-01

Summary The mammalian blood system contains a multitude of distinct mature cell lineages adapted to serve diverse functional roles. Mutations that abrogate the development or function of one or more of these lineages can lead to profound adverse consequences, such as immunodeficiency, autoimmunity, or anemia. Replacement of hematopoietic stem cells (HSCs) that carry such mutations with HSCs from a healthy donor can reverse such disorders, but because the risks associated with the procedure are often more serious than the blood disorders themselves, bone marrow transplantation is generally not used to treat a number of relatively common inherited blood diseases. Aside from a number of other problems, risks associated with cytoreductive treatments that create "space" for donor HSCs, and the slow kinetics with which immune competence is restored following transplantation hamper progress. This review will focus on how recent studies using experimental model systems may direct future efforts to implement routine use of HSC transplantation to cure inherited blood disorders. PMID:18651698

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

PubMed Central

Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

2012-01-01

Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

The impact of HIV-related stigma on the lives of HIV-positive women: an integrated literature review.

PubMed

Ho, Szu-Szu; Holloway, Aisha

2016-01-01

To critically explore how Human Immunodeficiency Virus-related stigma impacts on the lives of Human Immunodeficiency Virus-positive women through an integrative review of the literature. Throughout history Human Immunodeficiency Virus infection has been associated with sex trade, injecting drug use and other deviant behaviours within society. These historical associations can lead to the generation of negative perceptions of Human Immunodeficiency Virus-positive women. As such, women who contract Human Immunodeficiency Virus infection can be susceptible to societal stigma. An integrative literature review. To identify the publications on the impact of Human Immunodeficiency Virus-related stigma among women, a search was performed using the following databases: CINAHL, Medline, PsycINFO, EMBASE, and Applied Social Sciences Index and Abstract covering the period from 2000-2014. The following key words were included in the search: 'women', 'Human Immunodeficiency Virus', and 'stigma'. Twenty-six articles were retrieved and reviewed. From the results, four key themes merged in relation to the impact of Human Immunodeficiency Virus-related stigma on Human Immunodeficiency Virus-positive women's lives: the individual, relationships, work and the community. Despite great advances in the management and treatment of those who are Human Immunodeficiency Virus positive, it appears the lives of many women living with Human Immunodeficiency Virus remain greatly affected by their Human Immunodeficiency Virus infection with gender-specific stigma and stereotypes. Having a holistic understanding of this impact offers the potential for those responsible for the funding and draws the attention of researchers and policy makers on promoting medical services specifically for Human Immunodeficiency Virus-positive women, minimising social stigmatisation towards this client group, and optimising their health outcomes. In an attempt to amplify Human Immunodeficiency Virus-positive women's ability to resist social injustice, obtain support and optimise their health outcomes, nurses should expand their roles and work with professionals from different sectors to ensure the provision of comprehensive care to women with Human Immunodeficiency Virus infection. © 2015 John Wiley & Sons Ltd.

Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation.

PubMed

Cohen, Jonathan M; Sebire, Neil J; Harvey, Julia; Gaspar, H Bobby; Cathy, Cale; Jones, Alison; Rao, Kanchan; Cubitt, David; Amrolia, Persis J; Davies, E Graham; Veys, Paul

2007-09-15

Lymphoproliferative disease (LPD) is a recognized complication of primary immunodeficiency (PID) and immunodysregulatory syndromes. Historically, it has a very poor outcome. For patients surviving LPD, myeloablative hematopoietic stem cell transplantation (SCT) was the only cure for the underlying PID, with a high risk of developing posttransplantation complications, including recurrent lymphoproliferative disease. We describe 8 patients with a range of PID and immunodysregulatory syndromes complicated by LPD. After initial treatment of the LPD (including the use of anti-CD20 monoclonal antibody, rituximab, in 6 of the patients), all patients underwent reduced-intensity conditioning (RIC) SCT with prospective monitoring for Epstein-Barr virus (EBV) viremia. After transplantation, 3 patients received rituximab, and 3 patients received prophylactic EBV-specific cytotoxic T-lymphocytes. Only 1 patient developed recurrent LPD posttransplantation, which responded to rituximab. All patients who underwent transplantation survive free of LPD and are cured of their PID at a median follow-up of 4 years (range, 1-7 years). With careful monitoring and pre-emptive therapy, we advocate this RIC SCT approach to patients with PID who have pre-existing EBV-LPD.

Primary intestinal lymphangiectasia in an elderly female patient

PubMed Central

Huber, Xaver; Degen, Lukas; Muenst, Simone; Trendelenburg, Marten

2017-01-01

Abstract Protein loss via the gut can be caused by a number of gastrointestinal disorders, among which intestinal lymphangiectasia has been described to not only lead to a loss of proteins but also to a loss of lymphocytes, resembling secondary immunodeficiency. We are reporting on a 75-year-old female patient who came to our hospital because of a minor stroke. She had no history of serious infections. During the diagnostic work-up, we detected an apparent immunodeficiency syndrome associated with primary intestinal lymphangiectasia. Trying to characterize the alterations of the immune system, we not only found hypogammaglobulinemia and lymphopenia primarily affecting CD4+, and also CD8+ T cells, but also marked hypocomplementemia affecting levels of complement C4, C2, and C3. The loss of components of the immune system most likely was due to a chronic loss of immune cells and proteins via the intestinal lymphangiectasia, with levels of complement components following the pattern of protein electrophoresis. Thus, intestinal lymphangiectasia should not only be considered as a potential cause of secondary immune defects in an elderly patient, but can also be associated with additional hypocomplementemia. PMID:28767614

Spondylodiscitis Due to Aspergillus terreus in an Immunocompetent Host: Case Report and Literature Review.

PubMed

Comacle, Pauline; Le Govic, Yohann; Hoche-Delchet, Cyril; Sandrini, Jeremy; Aguilar, Claire; Bouyer, Benjamin; Blanchi, Sophie; Penn, Pascale

2016-08-01

Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen responsible for various infections in human beings. However, bone and joint involvement is uncommon. We report a rare case of A. terreus spondylodiscitis in a 20-year-old male with a past history of recurrent, incompletely treated pulmonary tuberculosis. Clinical signs at the time of admission included cough, low-grade fever, general weakness and left-sided back pain. Histological examination of spinal biopsy samples revealed lesions of necrosis, granulomatous inflammation and septate hyphae with acute-angle branching. A. terreus was recovered from culture. The patient received antifungal therapy with voriconazole plus caspofungin and underwent surgical debridement. Further investigations revealed no cause of primary immunodeficiency such as chronic granulomatous disease, severe combined immunodeficiency syndrome or disorders of the IL-12/IFNγ signaling pathway. Moreover, HIV serological tests resulted negative and the patient was not under immunosuppressive therapy. Unfortunately, owing to precarity and medication non-adherence, vertebral sequelae occurred. This new report emphasizes the need to consider a fungal infection in patients with spondylodiscitis, regardless of the immune status.

Effects of HIV-1 on Cognition in Humanized NSG Mice

NASA Astrophysics Data System (ADS)

Akhter, Sidra Pervez

Host species specificity of human immunodeficiency virus (HIV) creates a challenge to study the pathology, diagnostic tools, and therapeutic agents. The closely related simian immunodeficiency virus and studies of neurocognitive impairments on transgenic animals expressing partial viral genome have significant limitations. The humanized mice model provides a small animal system in which a human immune system can be engrafted and immunopathobiology of HIV-1 infection can be studied. However, features of HIV-associated neurocognitive disorders (HAND) were not evaluated in this model. Open field activity test was selected to characterize behavior of original strain NOD/scid-IL-2Rgammac null (NSG) mice, effects of engraftment of human CD34+ hematopoietic stem cells (HSCs) and functional human immune system (huNSG), and finally, investigate the behavior changes induced by chronic HIV-1 infection. Long-term infected HuNSG mice showed the loss of working memory and increased anxiety in the open field. Additionally, these animals were utilized for evaluation of central nervous system metabolic and structural changes. Detected behavioral abnormalities are correlated with obtained neuroimaging and histological abnormalities published.

Higher plasma CD4 lymphocyte count correlates with better cognitive function in human immunodeficiency virus-acquired immunodeficiency syndrome (HIV-AIDS) patients

NASA Astrophysics Data System (ADS)

Fitri, F. I.; Rambe, A. S.; Fitri, A.

2018-03-01

Neurocognitive disorders in HIV-AIDS are still prevalent despite the use of antiretroviral therapy and seem to be under-recognized. Plasma lymphocyte CD4 count is a marker for general immunology status, but its association with cognitive function remains unclear. The aim of this study was to determine the correlation between plasma CD4 lymphocyte and cognitive function in HIV-AIDS patients.This was a cross-sectional study involving 48 HIV-AIDS patients. All subjects underwent physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts.This study included 48 subjects consisted of 29 males (60.4%) and 19 females (39.6%). The mean age was 39.17±11.21 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r=0.347, p=0.016).Higher plasma CD4 lymphocyte count is correlated with better cognitive function in HIV-AIDS patients.

The development and psychometric analysis of the Chinese HIV-Related Fatigue Scale.

PubMed

Li, Su-Yin; Wu, Hua-Shan; Barroso, Julie

2016-04-01

To develop a Chinese version of the human immunodeficiency virus-related Fatigue Scale and examine its reliability and validity. Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus-positive people has not yet been developed for use in Chinese-speaking countries. A methodologic study involving instrument development and psychometric evaluation was used. The human immunodeficiency virus-related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus-positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's α for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test-retest reliability. The correlation between the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus-related Fatigue Scale scores of human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. The internal consistency and test-retest reliability of the Chinese version of the human immunodeficiency virus-related Fatigue Scale were 0·97 and 0·686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus-related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus-related Fatigue Scale could be used to effectively distinguish fatigue differences between the human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without. The Chinese version of the human immunodeficiency virus-related Fatigue Scale presents good reliability and validity through a robust psychometric analysis. This scale can be appropriately applied to human immunodeficiency virus-positive patients by clinical staff and case managers in Chinese-speaking countries. The Chinese version of the human immunodeficiency virus-related Fatigue Scale is an effective and comprehensive tool that can help clinical professionals measure the frequency, strength and impact on the quality of life of fatigue in Chinese human immunodeficiency virus-positive patients. © 2016 John Wiley & Sons Ltd.

Autoimmunity and primary immunodeficiency: two sides of the same coin?

PubMed

Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

2017-12-19

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.

Appendectomy in patients with human immunodeficiency virus: Not as bad as we once thought.

PubMed

Smith, Michael C; Chung, Paul J; Constable, Yohannes C; Boylan, Matthew R; Alfonso, Antonio E; Sugiyama, Gainosuke

2017-04-01

The number of patients living with human immunodeficiency virus and acquired immunodeficiency syndrome is growing due to advances in antiretroviral therapy. Existing literature on appendectomy within this patient population has been limited by small sample sizes. Therefore, we used a large, multiyear, nationwide database to study this topic comprehensively. Using the Nationwide Inpatient Sample, we identified 338,805 patients between 2005 and 2012 who underwent laparoscopic or open appendectomy for acute appendicitis. Interval appendectomies were excluded. We used multivariable adjusted regression models to test differences between patients with human immunodeficiency virus without acquired immunodeficiency syndrome and a reference group, as well as human immunodeficiency virus with acquired immunodeficiency syndrome and a reference group, with regard to duration of stay, hospital charges, in-hospital complications, and in-hospital mortality. Models were adjusted for patient age, sex, race, insurance, socioeconomic status, Elixhauser comorbidity score, and appendix perforation. There were 1,291 (0.38%) patients with human immunodeficiency virus, among which 497 (0.15%) patients had acquired immunodeficiency syndrome. In regression analysis, human immunodeficiency virus alone was not associated with adverse outcomes, while acquired immunodeficiency syndrome alone was associated with longer duration of stay (incidence rate ratio 1.40 [1.37-1.57 95% confidence interval], P < .0001), increased total charges (exponentiated coefficient 1.16 [1.10-1.23 95% confidence interval], P < .0001), and increased risk of postoperative infection (odds ratio 2.12 [1.44-3.13 95% confidence interval], P = .0002). Patients with acquired immunodeficiency syndrome who undergo appendectomy for acute appendicitis are subject to longer and more expensive hospital admissions and have greater rates of postoperative infections while patients with human immunodeficiency virus alone are not at risk for adverse outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

What motivates use of community-based human immunodeficiency virus testing in rural South Africa?

PubMed Central

Upadhya, Devesh; Moll, Anthony P; Brooks, Ralph P; Friedland, Gerald; Shenoi, Sheela V

2016-01-01

Despite substantial progress in implementing human immunodeficiency virus testing, challenges remain in achieving widespread uptake particularly in rural resource-limited settings. We sought to understand motivations for human immunodeficiency virus testing in a community-based human immunodeficiency virus testing programme in rural South Africa. We conducted a questionnaire survey in participants undergoing voluntary human immunodeficiency virus testing within an ongoing community-based integrated human immunodeficiency virus/TB intensive case finding programme at congregate rural settings. Participants responded to a six-item non-mutually exclusive motivations survey which included the topics of feeling ill, recent HV exposure, risky lifestyle, illness in a family member, and pregnancy. Among 2068 respondents completing the survey, 1393 (67.4%) were women, median age was 40 years (IQR 19–56), and 1235 (59.7%) were first time testers. Among all testers, 142 (6.9%) were human immunodeficiency virus-positive with median CD4 count 346 (IQR 218–542). Community-based testing for human immunodeficiency virus is acceptable and meets the needs of community members in rural South Africa. Motivations for human immunodeficiency virus testing at the community level are complex and differ according to gender, age, site of community testing, and human immunodeficiency virus status. These differences can be utilised to improve the focus and yield of community-based human immunodeficiency virus screening. PMID:26134323

Toll-like receptors (TLRs) and immune disorders.

PubMed

Akashi-Takamura, Sachiko; Miyake, Kensuke

2006-10-01

Upon the invasion of pathogens, the immune system needs to mount defense responses immediately. Over the past 10 years, Toll-like receptors (TLRs) have been discovered in mammals and defined as pathogen sensors. TLRs are considered to bind directly to ligands, discriminate them immediately, and induce defense responses when appropriate. We here review microbial recognition by TLRs, downstream signaling, and the relationship of TLRs to susceptibility to infectious diseases and immune disorders. Recent reports have revealed a requirement for co-receptors in TLR responses. A TLR signaling pathway is required for protection against infectious diseases, but excessive signaling may lead to allergies, autoimmune diseases, or atherosclerosis. In humans, several deficiencies of signaling molecules downstream of TLRs, and TLR polymorphisms that affect recognition or signaling, were reported to cause immunodeficiencies. It is important to understand how TLR signaling is controlled.

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.

PubMed

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

2010-12-01

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.

Deletion of Fanca or Fancd2 dysregulates Treg in mice.

PubMed

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

2014-03-20

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

Influence of Family Structure and School Variables on Behavior Disorders of Children

ERIC Educational Resources Information Center

Lindholm, Byron W.; And Others

1977-01-01

This study examined the influence of family structure and school variables on behavior disorders of children (N=1,162). Results indicated grade in school, sex, social class, ordinal position in the family, and teacher were important variables in the determination of behavior disorders. (Author)

The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren decoction by serum metabonomics approach.

PubMed

Niu, Xiaoyi; He, Bosai; Du, Yiyang; Sui, Zhenyu; Rong, Weiwei; Wang, Xiaotong; Li, Qing; Bi, Kaishun

2018-06-01

Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions, has been most commonly used in Asian countries and reported to inhibit the process of immunodeficiency insomnia. Polysaccharide is important component which also contributes to the role of immunoprotective and sedative hypnotic effects. This study was aimed to explore the immunoprotective and sedative hypnotic mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics approach. With this purpose, complex physical and chemical immunodeficiency insomnia models were firstly established according to its multi-target property. Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to determine endogenous metabolites. Then, principal component analysis was used to distinguish the groups, and partial least squares discriminate analysis was carried out to confirm the important variables. The serum metabolic profiling was identified and pathway analysis was performed after the total polysaccharide administration. The twenty-one potential biomarkers were screened, and the levels were all reversed to different degrees in the total polysaccharide treated groups. These potential biomarkers were mainly related to vitamin, sphingolipid, bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated that total polysaccharide could inhibit insomnia triggered by immunodeficiency stimulation through regulating those metabolic pathways. This study provides a useful approach for exploring the mechanism and evaluating the efficacy of total polysaccharide from Suanzaoren decoction. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of Prevalence and Determinants of Occupational Exposure to HIV Infection among Healthcare Workers in Selected Health Institutions in Debre Berhan Town, North Shoa Zone, Amhara Region, Ethiopia, 2014

PubMed Central

Aynalem Tesfay, Filmawit; Dejenie Habtewold, Tesfa

2014-01-01

Introduction. Health care workers are exposed to different kinds of occupational hazards due to their day to day activities. The most common occupational exposure like body fluids is a potential risk of transmission of blood-borne infection like human immunodeficiency virus. Objective. To assess the prevalence and determinants of occupational exposure to human immunodeficiency virus infection. Methods and Materials. A descriptive cross-sectional institution based study was conducted in selected four health institutions in Debre Berhan town. Quantitative and qualitative data were collected using semistructured interviewer administered questionnaire. The frequency distribution of dependent and independent variables was worked out and presented using frequency table, graph, and chart. Result. The overall prevalence of occupational exposure of the health care workers was found to be 88.6% (n = 187) in the past 12 months. Contact to potentially infectious body fluids accounts for the largest proportion (56.7%) followed by needle stick injury (31.5%) and glove breakage (28.8%). Conclusion. In this study majority (88.6%) of the health care workers had a risky occupational hazard that exposed them to human immunodeficiency virus infection during the past 12 months. The statistically significant determinant factors were professional status, working room, and time of personal protective equipment usage. PMID:25478213

Assessment of Prevalence and Determinants of Occupational Exposure to HIV Infection among Healthcare Workers in Selected Health Institutions in Debre Berhan Town, North Shoa Zone, Amhara Region, Ethiopia, 2014.

PubMed

Aynalem Tesfay, Filmawit; Dejenie Habtewold, Tesfa

2014-01-01

Introduction. Health care workers are exposed to different kinds of occupational hazards due to their day to day activities. The most common occupational exposure like body fluids is a potential risk of transmission of blood-borne infection like human immunodeficiency virus. Objective. To assess the prevalence and determinants of occupational exposure to human immunodeficiency virus infection. Methods and Materials. A descriptive cross-sectional institution based study was conducted in selected four health institutions in Debre Berhan town. Quantitative and qualitative data were collected using semistructured interviewer administered questionnaire. The frequency distribution of dependent and independent variables was worked out and presented using frequency table, graph, and chart. Result. The overall prevalence of occupational exposure of the health care workers was found to be 88.6% (n = 187) in the past 12 months. Contact to potentially infectious body fluids accounts for the largest proportion (56.7%) followed by needle stick injury (31.5%) and glove breakage (28.8%). Conclusion. In this study majority (88.6%) of the health care workers had a risky occupational hazard that exposed them to human immunodeficiency virus infection during the past 12 months. The statistically significant determinant factors were professional status, working room, and time of personal protective equipment usage.

Survey of knowledge, attitude, and practice regarding reproductive health among urban men in China: a descriptive study.

PubMed

Zhang, Ling; Gong, Rui-Long; Han, Qing-Rong; Shi, Yu-Qin; Jia, Quan-An; Xu, Shan-Dan; Wang, Le-Qun; Zhu, Chang-Cai

2015-01-01

There has been little focus on men's reproductive health (RH) in China. This descriptive study conducted in Yiling District, Yichang, China, surveyed male knowledge of sexual physiology and RH to assess levels of knowledge, attitudes and practices (KAPs) regarding prevention of sexually transmitted diseases (STDs). A total of 3933 men, aged 18-59 years (mean, 40.3 years), were recruited by cluster random sampling. They completed a questionnaire in the presence of an interviewer, with items related to subject characteristics, RH knowledge, and subjective symptoms of the reproductive system. Physical examination and reproductive system disease diagnosis were performed. Participants' occupations were predominantly skilled labor (80.5%). Nearly four-fifths (78.5%) respondents had at least one reproductive disease. Over half of respondents were aware of and declared a positive attitude about sexual physiology and safe sex, and 70% of them selected to visit a doctor when they had a reproductive disorder. However, only 41.9% believed human immunodeficiency virus/acquired immunodeficiency syndrome could be transmitted through breastfeeding, and 64.6% incorrectly thought they could avoid contracting STDs by cleaning their genitals after intercourse. In addition, 45% discriminated against and were unwilling to be friends with infected persons. Nearly 45% of those with a reproductive system disorder refused to discuss it with friends or family members. These results indicate that this cohort of Chinese men had a certain degree of KAP about RH, whereas some aspects require further public health education in the general population. It is necessary to disseminate accurate knowledge of STD risk in China based on sociodemographic characteristics.

24 CFR 574.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Grantee and Secretary are defined in 24 CFR part 5. Acquired immunodeficiency syndrome (AIDS) or related diseases means the disease of acquired immunodeficiency syndrome or any conditions arising from the etiologic agent for acquired immunodeficiency syndrome, including infection with the human immunodeficiency...

24 CFR 574.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Grantee and Secretary are defined in 24 CFR part 5. Acquired immunodeficiency syndrome (AIDS) or related diseases means the disease of acquired immunodeficiency syndrome or any conditions arising from the etiologic agent for acquired immunodeficiency syndrome, including infection with the human immunodeficiency...

24 CFR 574.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Grantee and Secretary are defined in 24 CFR part 5. Acquired immunodeficiency syndrome (AIDS) or related diseases means the disease of acquired immunodeficiency syndrome or any conditions arising from the etiologic agent for acquired immunodeficiency syndrome, including infection with the human immunodeficiency...

Determinants of domestic violence among women attending an human immunodeficiency virus voluntary counseling and testing center in Bangalore, India.

PubMed

Chandrasekaran, Varalakshmi; Krupp, Karl; George, Ruja; Madhivanan, Purnima

2007-05-01

Violence against women is a global phenomenon that cuts across all social and economic classes. This study was designed to measure the prevalence and correlates of domestic violence (DV) among women seeking services at a voluntary counseling and testing (VCT) center in Bangalore, India. A cross-sectional survey was conducted among women visiting an human immunodeficiency virus (HIV) VCT center in Bangalore, between September and November 2005. An interviewer-administered questionnaire was used to collect information about violence and other variables. Univariable associations with DV were made using Pearson Chi-squared test for categorical variables and Student t-test or the Mann-Whitney test for continuous variables. Forty-two percent of respondents reported DV, including physical abuse (29%), psychological abuse (69%) and sexual abuse (1%). Among the women who reported violence of any kind, 67% also reported that they were HIV seropositive. The most common reasons reported for DV included financial problems (38%), husband's alcohol use (29%) and woman's HIV status (18%). Older women (P < 0.001) and those with low income levels were the most likely to have experienced DV (P = 0.02). Other factors included husband's education, HIV seropositivity and alcohol or tobacco use (P < 0.001). This study found DV levels comparable to other studies from around the world. The findings highlight the need for additional training among health care providers in VCT centers in screening for DV, detection of signs of physical abuse and provisions and referrals for women suffering from domestic partner violence.

Primary Immunodeficiency Diseases in Aguascalientes, Mexico: Results from an Educational Program.

PubMed

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

2016-04-01

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.

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report

PubMed Central

2011-01-01

Introduction Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. Case presentation A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. Conclusions These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life. PMID:21892961

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report.

PubMed

Mendes, Edmar Lacerda; Ribeiro Andaki, Alynne Christian; Brito, Ciro José; Córdova, Cláudio; Natali, Antônio José; Santos Amorim, Paulo Roberto Dos; de Oliveira, Leandro Licursi; de Paula, Sérgio Oliveira; Mutimura, Eugene

2011-09-05

Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.

Classification of deaths in women with human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth.

PubMed

Brayner, Manuella Coutinho; Alves, Sandra Valongueiro

2017-01-01

To reclassify deaths of women infected with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth in the State of Pernambuco, Brazil, from 2000 to 2010. A descriptive exploratory study, developed from the following steps: translation to Portuguese of the item "HIV and aids" of the United Nations document "The WHO application of ICD-10 to deaths during pregnancy, childbirth and the puerperium: DCI MM 2012"; development of a classification algorithm of deaths of women living with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth; and reclassification of deaths by a group of experts. Among the 25 reclassified deaths, 12 were due to human immunodeficiency virus/acquired immunodeficiency syndrome, and pregnancy condition was coexisting; 9 were reclassified as indirect maternal death, with O98.7 code, proposed by the World Health Organization; 2 as direct/indirect maternal death; and 2 were considered indeterminate. The reclassification showed a possible pattern of change in maternal mortality, since most of the deaths were attributed to the virus and may lead to a reduction in deaths from maternal causes. The algorithm will subsidize the use of the new classification of maternal death and human immunodeficiency virus/acquired immunodeficiency syndrome.

Development of lifetime comorbidity in the WHO World Mental Health (WMH) Surveys

PubMed Central

Kessler, Ronald C.; Ormel, Johan; Petukhova, Maria; McLaughlin, Katie A.; Green, Jennifer Greif; Russo, Leo J.; Stein, Dan J.; Zaslavsky, Alan M; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Andrade, Laura; Benjet, Corina; de Girolamo, Giovanni; de Graaf, Ron; Demyttenaere, Koen; Fayyad, John; Haro, Josep Maria; Hu, Chi yi; Karam, Aimee; Lee, Sing; Lepine, Jean-Pierre; Matchsinger, Herbert; Mihaescu-Pintia, Constanta; Posada-Villa, Jose; Sagar, Rajesh; Üstün, T. Bedirhan

2010-01-01

CONTEXT Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the WHO World Mental Health (WMH) surveys. SETTING/PARTICIPANTS Nationally or regionally representative community surveys in 14 countries with a total of 21,229 respondents. MAIN OUTCOME MEASURES First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the WHO Composite International Diagnostic Interview (CIDI). RESULTS Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (i.e., internalizing or externalizing) associations were generally stronger than between-domain associations. The vast majority of time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity disorder and oppositional-defiant disorder (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered here. These common pathways should be the focus of future research on the development of comorbidity, although several important pair-wise associations that cannot be accounted for by latent variables also exist that warrant further focused study. PMID:21199968

78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

...] Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs... entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment.'' The... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs...

Characteristics of methadone maintenance treatment patients prescribed opioid analgesics.

PubMed

Glenn, Matthew C; Sohler, Nancy L; Starrels, Joanna L; Maradiaga, Jeronimo; Jost, John J; Arnsten, Julia H; Cunningham, Chinazo O

2016-01-01

Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics. We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012 to 2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients' report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-square tests, t tests, and Mann-Whitney U tests. Of 611 MMT patients, most reported chronic pain (62.0%), hepatitis C virus (HCV) infection (52.1%), and current use of illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and chronic pain (aOR = 7.6, 95% CI: 4.6-12.6). Among MMT patients primarily in 3 Bronx clinics, nearly one third reported taking prescribed opioid analgesics. Compared with patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients.

Risky sexual behavior among patients in Turkey with bipolar disorder, schizophrenia, and heroin addiction.

PubMed

Hariri, Aytul Gursu; Karadag, Figen; Gokalp, Peykan; Essizoglu, Altan

2011-08-01

Risky sexual behavior associated with such sexually transmitted infections (STIs) as hepatitis B and C, herpes, Treponema pallidum, and Neisseria gonorrhoeae, is more frequent among psychiatric patients and parenteral drug abusers than the general population. The aim of this study was to investigate risky sexual behavior in psychiatric outpatients diagnosed with schizophrenia (SCH), bipolar disorder, and heroin addiction (HA), and to compare them with those observed in healthy controls. The study group (N = 485; 234 females and 251 males) consisted of patients that consecutively presented to Bakırkoy State and Training Hospital for Psychiatric and Neurological Diseases in Istanbul and normal healthy controls. The chi-squared test was used for comparisons between groups and categorical variables. One-way analysis of variance (post-hoc Bonferroni test) was used for demographic data. A 22-item questionnaire for collecting demographic, illness history, and sexual activity data, and a structured 23-item form for collecting data on risky sexually behavior were administered to the participants. In all, 10% of the participants had a positive history for STIs. The majority of risky sexual behaviors was observed among the HA patients. The frequency of being sexually assaulted and having homosexual acts among the SCH group were higher. None of the patients had a positive human immunodeficiency virus (HIV) test result. The frequency of positivity for hepatitis B and C markers was highest among the HA patients. The provision of information and training about all STIs and risky sexual behavior should become routine in the treatment of mentally ill patients, especially those that abuse drugs. © 2011 International Society for Sexual Medicine.

Examining Affect and Perfectionism in Relation to Eating Disorder Symptoms among Women with Anorexia Nervosa

PubMed Central

Lavender, Jason M.; Mason, Tyler B.; Utzinger, Linsey M.; Wonderlich, Stephen A.; Crosby, Ross D.; Engel, Scott G.; Mitchell, James E.; Le Grange, Daniel; Crow, Scott J.; Peterson, Carol B.

2016-01-01

This study examined personality and affective variables in relation to eating disorder symptoms in anorexia nervosa (AN). Women (N=118) with DSM-IV AN completed baseline questionnaires (Beck Depression Inventory, Frost Multidimensional Perfectionism Scale) and interviews (Eating Disorder Examination, Yale-Brown-Cornell Eating Disorder Scale), followed by two weeks of ecological momentary assessment (EMA) involving multiple daily reports of affective states and eating disorder behaviors. Hierarchical regression analyses were conducted using eating disorder symptoms as dependent variables (i.e., EMA binge eating, EMA self-induced vomiting, eating disorder rituals, eating disorder preoccupations, dietary restraint). Predictor variables were maladaptive perfectionism (baseline), depressive symptoms (baseline), and affect lability (EMA). Results revealed that affect lability was independently associated with binge eating, whereas depressive symptoms were independently associated with self-induced vomiting. Depressive symptoms were independently associated with eating disorder rituals, whereas both depressive symptoms and maladaptive perfectionism were independently associated with eating disorder preoccupations. Finally, maladaptive perfectionism and affect lability were both independently associated with dietary restraint. This pattern of findings suggests the importance of affective and personality constructs in relation to eating disorder symptoms in AN and may highlight the importance of targeting these variables in the context of treatment. PMID:27208513

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

PubMed

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

PubMed Central

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%. PMID:29333065

Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type

NASA Technical Reports Server (NTRS)

He, X. M.; Ruker, F.; Casale, E.; Carter, D. C.

1992-01-01

The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 degrees. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1

NASA Technical Reports Server (NTRS)

He, Xiao M.; Rueker, Florian; Casale, Elena; Carter, Daniel C.

1992-01-01

The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 deg. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

Comparison of an assay using signal amplification of the heat-dissociated p24 antigen with the Roche Monitor human immunodeficiency virus RNA assay.

PubMed

Pascual, Alvaro; Cachafeiro, Ada; Funk, Michele L; Fiscus, Susan A

2002-07-01

We compared an assay using signal amplification of a heat-dissociated p24 antigen (HDAg) with the Roche Monitor human immunodeficiency virus (HIV) RNA assay. The two assays gave comparable results when 130 specimens from 130 patients were tested (r = 0.60, P < 0.0001). The HDAg assay was almost as sensitive (85%) as the Roche HIV RNA kit (95%), just as specific (25 negative results from 25 HIV seronegative volunteers [100%]), less variable (mean log standard deviation of 0.07 compared to 0.11 when eight specimens were tested three or four times), and less expensive (reagent and labor costs, $8 versus $75). The assay appeared to be useful for monitoring established patients (n = 17) and identifying seroconverters (n = 4). HIV subtypes A to F were all recognized. This assay should be useful for monitoring patients in resource-poor countries and for monitoring vaccine recipients.

Best practices in LGBT care: A guide for primary care physicians.

PubMed

McNamara, Megan C; Ng, Henry

2016-07-01

Lesbian, gay, bisexual, and transgender (LGBT) people have unique healthcare needs. While all LGBT people are at an increased risk for mental health and substance abuse disorders, certain health conditions vary by group. Overweight and obesity are more common in lesbian and bisexual women, whereas sexual minority men are at increased risk for infections such as human immunodeficiency virus (HIV) and syphilis. Breast, cervical, and prostate cancer screening should be offered to all LGBT individuals according to national guidelines and with consideration of a transgender person's natal and surgical anatomy. Copyright © 2016 Cleveland Clinic.

Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

PubMed Central

Rakhmanov, Mirzokhid; Keller, Baerbel; Gutenberger, Sylvia; Foerster, Christian; Hoenig, Manfred; Driessen, Gertjan; van der Burg, Mirjam; van Dongen, Jacques J.; Wiech, Elisabeth; Visentini, Marcella; Quinti, Isabella; Prasse, Antje; Voelxen, Nadine; Salzer, Ulrich; Goldacker, Sigune; Fisch, Paul; Eibel, Hermann; Schwarz, Klaus; Peter, Hans-Hartmut; Warnatz, Klaus

2009-01-01

The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. CD21low B cells are polyclonal, unmutated IgM+IgD+ B cells but carry a highly distinct gene expression profile which differs from conventional naïve B cells. Interestingly, while clearly not representing a memory population, they do share several features with the recently defined memory-like tissue, Fc receptor-like 4 positive B cell population in the tonsils of healthy donors. CD21low B cells show signs of previous activation and proliferation in vivo, while exhibiting defective calcium signaling and poor proliferation in response to B cell receptor stimulation. CD21low B cells express decreased amounts of homeostatic but increased levels of inflammatory chemokine receptors. This might explain their preferential homing to peripheral tissues like the bronchoalveolar space of CVID or the synovium of rheumatoid arthritis patients. Therefore, as a result of the close resemblance to the gene expression profile, phenotype, function and preferential tissue homing of murine B1 B cells, we suggest that CD21low B cells represent a human innate-like B cell population. PMID:19666505

Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency.

PubMed

Fliegauf, Manfred; Bryant, Vanessa L; Frede, Natalie; Slade, Charlotte; Woon, See-Tarn; Lehnert, Klaus; Winzer, Sandra; Bulashevska, Alla; Scerri, Thomas; Leung, Euphemia; Jordan, Anthony; Keller, Baerbel; de Vries, Esther; Cao, Hongzhi; Yang, Fang; Schäffer, Alejandro A; Warnatz, Klaus; Browett, Peter; Douglass, Jo; Ameratunga, Rohan V; van der Meer, Jos W M; Grimbacher, Bodo

2015-09-03

Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Reduced numbers of circulating group 2 innate lymphoid cells in patients with common variable immunodeficiency.

PubMed

Geier, Christoph B; Kraupp, Sophie; Bra, David; Eibl, Martha M; Farmer, Jocelyn R; Csomos, Krisztian; Walter, Jolan E; Wolf, Hermann M

2017-11-01

Recent studies identified an emerging role of group 2 and 3 innate lymphoid cells (ILCs) as key players in the generation of T-dependent and T-independent antibody production. In this retrospective case-control study, CD117 + ILCs (including the majority of ILC2 and ILC3) were reduced in patients with common variable immunodeficiency (CVID). The reduction in CD117 + ILCs was distinctive to CVID and could not be observed in patients with X-linked agammaglobulinemia. Patients with a more pronounced reduction in CD117 + ILC numbers showed significantly lower numbers of peripheral MZ-like B cells and an increased prevalence of chronic, non-infectious enteropathy. Subsequent phenotyping of ILC subsets in CVID revealed that the reduction in CD117 + ILC numbers is due to a reduction in ILC2 numbers. In vitro expansion of CVID ILC2 in response to IL-2, IL-7, IL-25 and IL-33 was impaired. Furthermore, upregulation of MHCII and IL-2RA in response to IL-2, IL-7, IL-25 and IL-33 was impaired in CVID ILC2. Thus, our results indicate a dysregulation of ILC subsets with a reduction in ILC2 numbers in CVID, however, further studies are needed to explore whether ILC abnormalities are a primary finding or secondary to disease complications encountered in CVID. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Family climates: family factors specific to disturbed eating and bulimia nervosa.

PubMed

Laliberté, M; Boland, F J; Leichner, P

1999-09-01

More than a decade of research has characterized the families of individuals with bulimia and bulimia anorexia (Anorexia Nervosa, Binge/Purging Type) as less expressive, less cohesive, and experiencing more conflicts than normal control families. This two-part study investigated variables believed more directly related to disturbed eating and bulimia as contributing to a "family climate for eating disorders." In Study 1. a nonclinical sample of 324 women who had just left home for college and a sample of 121 mothers evaluated their families. Principal-components analyses revealed the same factor structure for both students and mothers, with Family Body Satisfaction, Family Social Appearance Orientation, and Family Achievement Emphasis loading together, representing the hypothesized family climate for eating disorders: the remaining variables loaded with the more traditional family process variables (conflict, cohesion, expressiveness), representing a more general family dysfunction. As predicted, the family climate for eating disorders factor score was a more powerful predictor of disturbed eating. Study 2 extended these findings into a clin ical population, examining whether the family climate for eating disorders variables would distinguish individuals with bulimia from both depressed and healthy controls. Groups of eating-disordered patients (n = 40) and depressed (n = 17) and healthy (n = 27) controls completed family measures. The eating-disordered group scored significantly higher on family climate variables than control groups. Family process variables distinguished clinical groups (depressed and eating disordered) from healthy controls, but not from one another. Controlling for depression removed group differences on family process variables, but family climate variables continued to distinguish the eating-disordered group from both control groups. Indications for further research are discussed.

SLEEP AND MENTAL DISORDERS: A META-ANALYSIS OF POLYSOMNOGRAPHIC RESEARCH

PubMed Central

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F.; Riemann, Dieter

2016-01-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, ADHD, and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the “Comprehensive Meta-Analysis” and “R” softwares. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges’g). Sources of variability, i.e., sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in one condition; however, no two conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in one single variable. PMID:27416139

[Discriminant analysis to predict the clinical diagnosis of primary immunodeficiencies: a preliminary report].

PubMed

Murata, Chiharu; Ramírez, Ana Belén; Ramírez, Guadalupe; Cruz, Alonso; Morales, José Luis; Lugo-Reyes, Saul Oswaldo

2015-01-01

The features in a clinical history from a patient with suspected primary immunodeficiency (PID) direct the differential diagnosis through pattern recognition. PIDs are a heterogeneous group of more than 250 congenital diseases with increased susceptibility to infection, inflammation, autoimmunity, allergy and malignancy. Linear discriminant analysis (LDA) is a multivariate supervised classification method to sort objects of study into groups by finding linear combinations of a number of variables. To identify the features that best explain membership of pediatric PID patients to a group of defect or disease. An analytic cross-sectional study was done with a pre-existing database with clinical and laboratory records from 168 patients with PID, followed at the National Institute of Pediatrics during 1991-2012, it was used to build linear discriminant models that would explain membership of each patient to the different group defects and to the most prevalent PIDs in our registry. After a preliminary run only 30 features were included (4 demographic, 10 clinical, 10 laboratory, 6 germs), with which the training models were developed through a stepwise regression algorithm. We compared the automatic feature selection with a selection made by a human expert, and then assessed the diagnostic usefulness of the resulting models (sensitivity, specificity, prediction accuracy and kappa coefficient), with 95% confidence intervals. The models incorporated 6 to 14 features to explain membership of PID patients to the five most abundant defect groups (combined, antibody, well-defined, dysregulation and phagocytosis), and to the four most prevalent PID diseases (X-linked agammaglobulinemia, chronic granulomatous disease, common variable immunodeficiency and ataxiatelangiectasia). In practically all cases of feature selection the machine outperformed the human expert. Diagnosis prediction using the equations created had a global accuracy of 83 to 94%, with sensitivity of 60 to 100%, specificity of 83 to 95% and kappa coefficient of 0.37 to 0.76. In general, the selection of features has clinical plausibility, and the practical advantage of utilizing only clinical attributes, infecting germs and routine lab results (blood cell counts and serum immunoglobulins). The performance of the model as a diagnostic tool was acceptable. The study's main limitations are a limited sample size and a lack of cross validation. This is only the first step in the construction of a machine learning system, with a wider approach that includes a larger database and different methodologies, to assist the clinical diagnosis of primary immunodeficiencies.

Respiratory problems in patients with ectodermal dysplasia syndromes.

PubMed

Fete, Timothy

2014-10-01

The ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a deficiency of ectoderm- and mesoderm-derived tissues and appendages, particularly hair, skin, teeth, and nails. Many of these disorders are associated with a greater risk of respiratory disease than found in the general population. There are no published papers that comprehensively describe these findings and the possible etiologies. Patients have been reported with dramatic decrease in mucous glands in the respiratory tract. Anatomic defects, including cleft palate, that predispose to respiratory infection, are associated with several of the ED syndromes. Atopy and immune deficiencies have been shown to have a higher prevalence in ED syndromes. Clinicians who care for patients affected by ED syndromes should be aware of the potential respiratory complications, and consider evaluation for structural anomalies, atopy and immunodeficiency in individuals with recurrent or chronic respiratory symptoms. © 2014 Wiley Periodicals, Inc.

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

Examining affect and perfectionism in relation to eating disorder symptoms among women with anorexia nervosa.

PubMed

Lavender, Jason M; Mason, Tyler B; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Le Grange, Daniel; Crow, Scott J; Peterson, Carol B

2016-07-30

This study examined personality and affective variables in relation to eating disorder symptoms in anorexia nervosa (AN). Women (N=118) with DSM-IV AN completed baseline questionnaires (Beck Depression Inventory, Frost Multidimensional Perfectionism Scale) and interviews (Eating Disorder Examination, Yale-Brown-Cornell Eating Disorder Scale), followed by two weeks of ecological momentary assessment (EMA) involving multiple daily reports of affective states and eating disorder behaviors. Hierarchical regression analyses were conducted using eating disorder symptoms as dependent variables (i.e., EMA binge eating, EMA self-induced vomiting, eating disorder rituals, eating disorder preoccupations, dietary restraint). Predictor variables were maladaptive perfectionism (baseline), depressive symptoms (baseline), and affect lability (EMA). Results revealed that affect lability was independently associated with binge eating, whereas depressive symptoms were independently associated with self-induced vomiting. Depressive symptoms were independently associated with eating disorder rituals, whereas both depressive symptoms and maladaptive perfectionism were independently associated with eating disorder preoccupations. Finally, maladaptive perfectionism and affect lability were both independently associated with dietary restraint. This pattern of findings suggests the importance of affective and personality constructs in relation to eating disorder symptoms in AN and may highlight the importance of targeting these variables in the context of treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spectrum of primary immunodeficiency disorders in Sri Lanka

PubMed Central

2013-01-01

Background While primary immunodeficiencies (PID has been recognized in the west for decades, recognition has been delayed in the third world. This study attempts to detail the spectrum of PID, the therapy provided, and constraints in the diagnosis and treatment in a middle income country such as Sri Lanka. Methods Nine hundred and forty two patients with recurrent infections and features suggestive of immune deficiency, referred from the entire country in a 4 year period, to the sole immunology unit in Sri Lanka were included. The following tests were performed. Full blood counts, serum Immunoglobulin and complement C3 and C4 levels, functional antibody levels, enumeration of lymphocyte subsets, in vitro and in vivo T cell functional assays,, nitroblue tetrazolium assay to diagnose chronic granulomatous disease, hair shaft assay to diagnose Griscelli syndrome. Sequencing of the common gamma chain to identify x linked severe combined immune deficiency, and X linked agammaglobulinemia was confirmed by assaying for Btk mutations by single sequence conformation polymorphism. HIV/AIDS was excluded in all patients. Results Seventy three patients were diagnosed with a primary immune deficiency. The majority (60.27%) had antibody deficiency. Common variable immune deficiency was the commonest (28.76%), followed by X linked agammaglobulinemia (XLA) (20.54%). Five patients had possible hyper IgM syndrome. Ten patients had severe combined immune deficiency (SCID), including 2 with x linked SCID, in addition to DiGeorge syndrome (2), ataxia telangiectasia (6), autosomal dominant hyper IgE syndrome (2), chronic granulomatous disease (4), leucocyte adhesion deficiency type 1 (2) and Griscelli syndrome (3). Patients with autoinflammatory, innate immune and complement defects could not be identified due to lack of facilities. Conclusions Antibody deficiency is the commonest PID, as in the west.IgA deficiency is rare. Autoinflammatory diseases, innate immune and complement deficiencies could not be identified due to lack of diagnostic facilities. Lack of awareness of PID among adult physicians result in delay in treatment of adult patients. While treatment of antibody deficiencies provided in state hospitals has extended life expectancy, there is no treatment available for severe T cell defects. PMID:24373416

Sleep and mental disorders: A meta-analysis of polysomnographic research.

PubMed

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F; Riemann, Dieter

2016-09-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, attention-deficit-hyperactivity disorder (ADHD), and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the "Comprehensive Meta-Analysis" and "R" software. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges' g). Sources of variability, that is, sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in 1 condition; however, no 2 conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in 1 single variable. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Song; J Willer; P Scherer

2011-12-31

Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent.more » We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.« less

Tele-Interpersonal Psychotherapy Acutely Reduces Depressive Symptoms in Depressed HIV-Infected Rural Persons: A Randomized Clinical Trial.

PubMed

Heckman, Timothy G; Heckman, Bernadette D; Anderson, Timothy; Lovejoy, Travis I; Markowitz, John C; Shen, Ye; Sutton, Mark

2017-01-01

Human immunodeficiency virus (HIV)-positive rural individuals carry a 1.3-times greater risk of a depressive diagnosis than their urban counterparts. This randomized clinical trial tested whether telephone-administered interpersonal psychotherapy (tele-IPT) acutely relieved depressive symptoms in 132 HIV-infected rural persons from 28 states diagnosed with Diagnostic and Statistical Manual of Mental Disorders-IV major depressive disorder (MDD), partially remitted MDD, or dysthymic disorder. Patients were randomized to either 9 sessions of one-on-one tele-IPT (n = 70) or standard care (SC; n = 62). A series of intent-to-treat (ITT), therapy completer, and sensitivity analyses assessed changes in depressive symptoms, interpersonal problems, and social support from pre- to postintervention. Across all analyses, tele-IPT patients reported significantly lower depressive symptoms and interpersonal problems than SC controls; 22% of tele-IPT patients were categorized as a priori "responders" who reported 50% or higher reductions in depressive symptoms compared to only 4% of SC controls in ITT analyses. Brief tele-IPT acutely decreased depressive symptoms and interpersonal problems in depressed rural people living with HIV.

Subjective complaints of cognitive symptoms are related to psychometric findings of memory deficits in patients with HIV-1 infection.

PubMed

Poutiainen, E; Elovaara, I

1996-05-01

Eighty-five subjects at various stages of human immunodeficiency virus (HIV-1) infection and 39 seronegative controls underwent neurological and neuropsychological evaluation to assess the relationship between cognitive test results and subjective complaints (cognitive, affective, motor, and other). The effect of psychiatric disorders on the association between cognitive performance and complaints of the patients was also examined. Patients with symptomatic infection had higher frequency of complaints than subjects at asymptomatic stage. Detailed neuropsychological examination confirmed a strong association between poor verbal memory and cognitive complaints. Poor performance on cognitive speed and flexibility was associated with motor complaints and motor abnormalities. These associations were not explained by psychiatric disorders or elevated depression questionnaire scores. Our observations indicate that, especially in symptomatic HIV-1 infection cognitive changes reported by patients often reflect "objective" cognitive decline, and may be the earliest signs of HIV-1 associated cognitive disorder. No direct relationship was observed between "subjective" complaints and neuropsychological performance of asymptomatic subjects. Understanding the significance of reported cognitive changes have important therapeutic implications.

Kaposi sarcoma and paracoccidioidomycosis in the same fragment of oral mucosa biopsy: a rare association in human immunodeficiency virus-positive patient. A case report.

PubMed

Pontes, Helder Antônio Rebelo; Guimarães, Douglas Magno; Pontes, Flávia Siroteau Corrêa; Paiva, Helena Borges; Pinto, Lara Carolina D'araujo; de Freitas Silva, Brunno Santos; Dos Santos Pinto, Décio

2011-02-01

The immunossuppression caused by HIV infection makes the affected individuals more susceptible to some diseases including infections, neoplasms, or even the association between them. Kaposi sarcoma (KS) is the most common AIDS-related neoplasm, featured as an angioproliferative disorder. Its cause seems to be related to the human herpesvirus type 8 and it is usually associated with lower CD4+ T cell count. Oral involvement is frequent, presenting red to blue-purplish plaques, maculaes, and nodules. On the other hand, paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. This mycosis is not commonly related to human immunodeficiency virus (HIV) infection, although PCM can be present in immunosuppression cases. Oral lesions, as granulomatous ulcers, are often identified in seropositive patients with PCM. A rare case, in which a male HIV-positive patient presented simultaneously Kaposi sarcoma and PCM in the same fragment of oral mucosa biopsy, is described. To the best of our knowledge, this concomitant association had not been previously described. Copyright © 2011 Elsevier Inc. All rights reserved.

In utero hematopoietic stem cell transfer: current status and future strategies.

PubMed

Surbek, D V; Gratwohl, A; Holzgreve, W

1999-07-01

Successful prenatal treatment of severe immunodeficiencies by allogeneic hematopoietic stem cell transplantation in utero has been reported. Though other diseases like hemoglobinopathies or storage diseases are potentially amenable to this novel therapeutic approach, no success has yet been achieved in recipients without severe immunodeficiency. Graft rejection by the developing fetus and/or lack of selective, competitive advantage of donor versus host stem cells preventing stable engraftment seem to be the major obstacles. Several strategies to overcome these hurdles are being explored in preclinical settings, including timing and repeated dosing of stem cell administration to the fetus, ex vivo modification of the transplant, using different fetal compartments as targets for early stem cell transfer, or inducing microchimerism for postnatal transplantation from the same donor. In addition, the exact definition of the basic concept of early fetal immunologic naivete and the understanding of the molecular basics of migration and homing in fetal hematopoiesis system seem mandatory for a successful approach. Gene therapy using ex vivo transduced autologous cord blood cells or direct gene targeting in utero are other potential means to correct hematopoietic and immunologic single gene disorders in utero, though this approach is still away from the stage of clinical trials.

Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature (“FILS syndrome”)

PubMed Central

Pachlopnik Schmid, Jana; Lemoine, Roxane; Nehme, Nadine; Cormier-Daire, Valéry; Revy, Patrick; Debeurme, Franck; Debré, Marianne; Nitschke, Patrick; Bole-Feysot, Christine; Legeai-Mallet, Laurence; Lim, Annick; de Villartay, Jean-Pierre; Picard, Capucine; Durandy, Anne; Fischer, Alain

2012-01-01

DNA polymerase ε (Polε) is a large, four-subunit polymerase that is conserved throughout the eukaryotes. Its primary function is to synthesize DNA at the leading strand during replication. It is also involved in a wide variety of fundamental cellular processes, including cell cycle progression and DNA repair/recombination. Here, we report that a homozygous single base pair substitution in POLE1 (polymerase ε 1), encoding the catalytic subunit of Polε, caused facial dysmorphism, immunodeficiency, livedo, and short stature (“FILS syndrome”) in a large, consanguineous family. The mutation resulted in alternative splicing in the conserved region of intron 34, which strongly decreased protein expression of Polε1 and also to a lesser extent the Polε2 subunit. We observed impairment in proliferation and G1- to S-phase progression in patients’ T lymphocytes. Polε1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. Our results evidence the developmental impact of a Polε catalytic subunit deficiency in humans and its causal relationship with a newly recognized, inherited disorder. PMID:23230001

Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).

PubMed

Booth, Claire; Gaspar, H Bobby

2009-01-01

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.

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

PubMed

Sauer, Aisha V; Mrak, Emanuela; Hernandez, Raisa Jofra; Zacchi, Elena; Cavani, Francesco; Casiraghi, Miriam; Grunebaum, Eyal; Roifman, Chaim M; Cervi, Maria C; Ambrosi, Alessandro; Carlucci, Filippo; Roncarolo, Maria Grazia; Villa, Anna; Rubinacci, Alessandro; Aiuti, Alessandro

2009-10-08

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children's growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling.

The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro.

PubMed

Kuciak, Monika; Gabus, Caroline; Ivanyi-Nagy, Roland; Semrad, Katharina; Storchak, Roman; Chaloin, Olivier; Muller, Sylviane; Mély, Yves; Darlix, Jean-Luc

2008-06-01

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44-61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.

The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro

PubMed Central

Kuciak, Monika; Gabus, Caroline; Ivanyi-Nagy, Roland; Semrad, Katharina; Storchak, Roman; Chaloin, Olivier; Muller, Sylviane; Mély, Yves; Darlix, Jean-Luc

2008-01-01

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44–61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties. PMID:18442994

Endoscopy of the upper gastrointestinal tract as a diagnostic tool for children with human immunodeficiency virus infection.

PubMed

Miller, T L; McQuinn, L B; Orav, E J

1997-05-01

The purpose of this study was to determine the prevalence of upper gastrointestinal tract lesions in children with human immunodeficiency virus (HIV) infection who undergo endoscopy of the upper gastrointestinal tract and to identify important clinical predictors of abnormal endoscopic results. All HIV-infected children who underwent endoscopy and were followed at Children's Hospital, Boston, from January 1985 to August 1994 were studied. The main outcome measure was endoscopic results, which were categorized into observational, histologic, and microbiologic findings. Potential predictors included height, weight, nutritional interventions, HIV disease stage, CD4 T-lymphocyte count, medications, active infections, and indications for endoscopy. Forty-three endoscopies in unique patients are reported. Most children had advanced HIV infection (67% acquired immunodeficiency syndrome, mean CD4 T-lymphocyte count z score = -2.71, weight z score = -2.04). An abnormal endoscopic finding was discovered in 93% of children and confirmed by histologic, microbiologic, or a combination of these studies in 72% of children. Thirty-five percent of children had an opportunistic pathogen identified endoscopically; 65% of these pathogens were previously undiagnosed. Observational findings often were poor indicators of histologic and microbiologic abnormalities. Independent predictors of abnormal histologic findings include younger age at endoscopy (odds ratio (OR) = 1.16 per year, 95% confidence interval (CI) (1.02, 1.33)) and guaiac-negative stools (OR = 16.7, 95% CI (1.92, 142.9)). Independent predictors of finding a pathogen at the time of endoscopy include a greater number of indications for endoscopy (OR = 2.6 per indication, 95% CI (1.3, 5.3)) and diagnosis of acquired immunodeficiency syndrome (OR = 16.4, 95% CI (1.3, 213)). No other gastrointestinal, nutritional, or immunologic parameters were significantly predictive of endoscopic outcomes. Medical management was changed in 70% of children because of the endoscopic findings. Endoscopy is a useful tool to direct therapy against peptic and infectious disorders of the upper gastrointestinal tract in children with HIV infection. Specific gastrointestinal symptoms are not useful predictors of abnormal results.

Effects of Escitalopram on Autonomic Function in Posttraumatic Stress Disorder Among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF).

PubMed

Ramaswamy, Sriram; Selvaraj, Vithyalakshmi; Driscoll, David; Madabushi, Jayakrishna S; Bhatia, Subhash C; Yeragani, Vikram

2015-01-01

Posttraumatic stress disorder is a chronic, debilitating condition that has become a growing concern among combat veterans. Previous research suggests that posttraumatic stress disorder disrupts normal autonomic responding and may increase the risk of cardiovascular disease and mortality. Measures of heart rate variability and QT interval variability have been used extensively to characterize sympathetic and parasympathetic influences on heart rate in a variety of psychiatric populations. The objective of this study was to better understand the effects of pharmacological treatment on autonomic reactivity in posttraumatic stress disorder. A 12-week, Phase IV, prospective, open-label trial of escitalopram in veterans with combat-related posttraumatic stress disorder and comorbid depression. An outpatient mental health clinic at a Veterans Affairs Medical Center. Eleven male veterans of Operations Enduring Freedom and Iraqi Freedom diagnosed with posttraumatic stress disorder and comorbid depression. Autonomic reactivity was measured by examining heart rate variability and QT interval variability. Treatment safety and efficacy were also evaluated pre- and post-treatment. We observed a reduction in posttraumatic stress disorder and depression symptoms from pre- to post-treatment, and escitalopram was generally well tolerated in our sample. In addition, we observed a decrease in high frequency heart rate variability and an increase in QT variability, indicating a reduction in cardiac vagal function and heightened sympathetic activation. These findings suggest that escitalopram treatment in patients with posttraumatic stress disorder and depression can trigger changes in autonomic reactivity that may adversely impact cardiovascular health.

Vaccine-associated Paralytic Poliomyelitis in Immunodeficient Children, Iran, 1995–2008

PubMed Central

Shahmahmoodi, Shohreh; Mamishi, Setareh; Aghamohammadi, Asghar; Aghazadeh, Nessa; Tabatabaie, Hamideh; Gooya, Mohammad Mehdi; Zahraei, Seyed Mohsen; Mousavi, Taha; Yousefi, Maryam; Farrokhi, Kobra; Mohammadpour, Masoud; Ashrafi, Mahmoud Reza; Nategh, Rakhshandeh

2010-01-01

To determine the prevalence of vaccine-associated paralytic poliomyelitis (VAPP) in immunodeficient infants, we reviewed all documented cases caused by immunodeficiency-associated vaccine-derived polioviruses in Iran from 1995 through 2008. Changing to an inactivated polio vaccine vaccination schedule and introduction of screening of neonates for immunodeficiencies could reduce the risk for VAPP infection. PMID:20587188

Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops.

PubMed

Kolchinsky, P; Kiprilov, E; Bartley, P; Rubinstein, R; Sodroski, J

2001-04-01

The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for CD4-independent replication were limited to the V2 loop-V1/V2 stem. Here we show that elimination of a single glycosylation site at asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4 at 4 degrees C than at 37 degrees C. In the absence of the V1/V2 loops, neither removal of the N-linked carbohydrate at asparagine 197 nor lowering of the temperature increased the CD4-independent phenotypes. A CCR5-binding conformation of gp120, achieved by CD4 interaction or by modification of temperature, glycosylation, or variable loops, was preferentially recognized by the monoclonal antibody 48d. These results suggest that the CCR5-binding region of gp120 is occluded by the V1/V2 variable loops, the position of which can be modulated by temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem.

Multisite Comparison of Anti-Human Immunodeficiency Virus Microbicide Activity in Explant Assays Using a Novel Endpoint Analysis ▿ †

PubMed Central

Richardson-Harman, Nicola; Lackman-Smith, Carol; Fletcher, Patricia S.; Anton, Peter A.; Bremer, James W.; Dezzutti, Charlene S.; Elliott, Julie; Grivel, Jean-Charles; Guenthner, Patricia; Gupta, Phalguni; Jones, Maureen; Lurain, Nell S.; Margolis, Leonid B.; Mohan, Swarna; Ratner, Deena; Reichelderfer, Patricia; Roberts, Paula; Shattock, Robin J.; Cummins, James E.

2009-01-01

Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development. PMID:19726602

Decision making under explicit risk is impaired in individuals with human immunodeficiency virus (HIV).

PubMed

Fujiwara, Esther; Tomlinson, Sara E; Purdon, Scot E; Gill, M John; Power, Christopher

2015-01-01

Human immunodeficiency virus (HIV) can affect the frontal-striatal brain regions, which are known to subserve decision-making functions. Previous studies have reported impaired decision making among HIV+ individuals using the Iowa Gambling Task, a task that assesses decision making under ambiguity. Previous study populations often had significant comorbidities such as past or present substance use disorders and/or hepatitis C virus coinfection, complicating conclusions about the unique contributions of HIV-infection to decision making. Decision making under explicit risk has very rarely been examined in HIV+ individuals and was tested here using the Game of Dice Task (GDT). We examined decision making under explicit risk in the GDT in 20 HIV+ individuals without substance use disorder or HCV coinfection, including a demographically matched healthy control group (n = 20). Groups were characterized on a standard neuropsychological test battery. For the HIV+ group, several disease-related parameters (viral load, current and nadir CD4 T-cell count) were included. Analyses focused on the GDT and spanned between-group (t-tests; analysis of covariance, ANCOVA) as well as within-group comparisons (Pearson/Spearman correlations). HIV+ individuals were impaired in the GDT, compared to healthy controls (p = .02). Their decision-making impairments were characterized by less advantageous choices and more random choice strategies, especially towards the end of the task. Deficits in the GDT in the HIV+ group were related to executive dysfunctions, slowed processing/motor speed, and current immune system status (CD4+ T-cell levels, ps < .05). Decision making under explicit risk in the GDT can occur in HIV-infected individuals without comorbidities. The correlational patterns may point to underlying fronto-subcortical dysfunctions in HIV+ individuals. The GDT provides a useful measure to assess risky decision making in this population and should be tested in larger studies.

Human herpesvirus 8 infections in patients with immunodeficiencies.

PubMed

Laurent, Camille; Meggetto, Fabienne; Brousset, Pierre

2008-07-01

In 1994, Chang et al described a novel herpesvirus in tissues from patients with Kaposi sarcoma, referred to as Kaposi sarcoma herpesvirus or human herpesvirus 8. They used a very sophisticated technique of molecular biology to isolate unknown DNA sequences from Kaposi sarcoma lesions, which were not present in normal tissues. It turned out that these sequences corresponded to a previously unrecognized gamma herpesvirus highly homologous to human herpesvirus 4 (Epstein-Barr virus) and to herpesvirus saimiri. Contrary to Epstein-Barr virus, human herpesvirus 8 is not ubiquitous. The seroprevalence of human herpesvirus 8 varies greatly worldwide, with 1% to 10% of people being infected in developed countries and up to 80% of infected individuals in some areas of sub-Saharan and equatorial Africa. Human herpesvirus 8 is associated with a limited spectrum of tumors, mostly observed in immunodeficient individuals with HIV infection. Beside Kaposi sarcoma and multicentric Castleman disease, human herpesvirus 8 is associated with primary effusion lymphoma, but unlike Epstein-Barr virus, human herpesvirus 8 is not involved in epithelial tumors. Different proteins of the virus can be detected in infected cells. Antibodies against the latent nuclear antigen 1 are available in routine pathology and represent a powerful tool to detect the virus in human tissues. Although Epstein-Barr virus is the most frequent causative agent of lymphomas in immunocompromised individuals, a systematic screening of such tumors with specific antibodies reveals that the implication of human herpesvirus 8 infection is probably underestimated. Recent descriptions of non-Hodgkin lymphoma in endemic areas, solid localizations of primary effusion lymphoma, and posttransplantation lymphoproliferations have expanded the spectrum of human herpesvirus 8-related lymphoproliferative disorders. In this review, we will be presenting an overview of the recent concepts regarding human herpesvirus 8 and related disorders.

Survey of knowledge, attitude, and practice regarding reproductive health among urban men in China: a descriptive study

PubMed Central

Zhang, Ling; Gong, Rui-Long; Han, Qing-Rong; Shi, Yu-Qin; Jia, Quan-An; Xu, Shan-Dan; Wang, Le-Qun; Zhu, Chang-Cai

2015-01-01

There has been little focus on men's reproductive health (RH) in China. This descriptive study conducted in Yiling District, Yichang, China, surveyed male knowledge of sexual physiology and RH to assess levels of knowledge, attitudes and practices (KAPs) regarding prevention of sexually transmitted diseases (STDs). A total of 3933 men, aged 18–59 years (mean, 40.3 years), were recruited by cluster random sampling. They completed a questionnaire in the presence of an interviewer, with items related to subject characteristics, RH knowledge, and subjective symptoms of the reproductive system. Physical examination and reproductive system disease diagnosis were performed. Participants’ occupations were predominantly skilled labor (80.5%). Nearly four-fifths (78.5%) respondents had at least one reproductive disease. Over half of respondents were aware of and declared a positive attitude about sexual physiology and safe sex, and 70% of them selected to visit a doctor when they had a reproductive disorder. However, only 41.9% believed human immunodeficiency virus/acquired immunodeficiency syndrome could be transmitted through breastfeeding, and 64.6% incorrectly thought they could avoid contracting STDs by cleaning their genitals after intercourse. In addition, 45% discriminated against and were unwilling to be friends with infected persons. Nearly 45% of those with a reproductive system disorder refused to discuss it with friends or family members. These results indicate that this cohort of Chinese men had a certain degree of KAP about RH, whereas some aspects require further public health education in the general population. It is necessary to disseminate accurate knowledge of STD risk in China based on sociodemographic characteristics. PMID:25532571

Congenital Tracheobronchomegaly (Mounier-Kuhn Syndrome) in a Woman with Human Immunodeficiency Virus: A Case Report.

PubMed

Fletcher, Amanda; Stowell, Justin; Jamoulis, Socrates

2017-04-04

Congenital tracheobronchomegaly (Mounier-Kuhn Syndrome, MKS) is a rare idiopathic disorder characterized by dilation of the central airways, including the trachea and first through fourth order bronchi. MKS disproportionately affects men and results in chronic respiratory tract infections. The diagnosis is made through the synthesis of clinical and radiological data. Here we report a unique case of MKS in a patient with human immunodeficiency virus (HIV) infection. A 45-year-old African American woman with a past medical history of HIV, tobacco and recreational drug abuse, chronic obstructive pulmonary disease, sleep apnea, and a 15-year history of recurrent respiratory infections presented with dyspnea, wheezing, a productive cough, increased yellow-green sputum production, and subjective fevers. Computerized tomography (CT) of the chest revealed striking dilation of the trachea and central bronchi. Fiberoptic bronchoscopy demonstrated a dilated trachea and bronchial tree with complete collapse of the trachea and bilateral mainstem bronchi during expiration. Serial imaging over 14 years allowed the radiologist to confidently diagnose her underlying disorder and recommend appropriate clinical management, which included mucolytics, chest physiotherapy, prophylactic vaccinations, and antibiotics during infectious exacerbations. To the best of our knowledge, there is only one reported case of MKS in the setting of HIV in the English literature. We report the second such case and outline the clinical presentation, diagnostic criteria, and management of MKS with the hope that increased awareness will prevent delayed or misdiagnosis for patients with MKS. This case highlights the common diagnostic delay for MKS and the need to include MKS in the differential diagnosis of recurrent respiratory tract infections.

Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection.

PubMed

Rosenthal, D; LeBoit, P E; Klumpp, L; Berger, T G

1991-02-01

We studied 13 patients with human immunodeficiency virus (HIV) infection and a chronic pruritic folliculitis that was unresponsive to systemic treatment with bactericidal anti-staphylococcal antibiotics. The skin eruption was characterized by multiple urticarial follicular papules scattered on the trunk (100%), the head and neck (85%), and the proximal aspect of the extremities (62%). Absolute peripheral eosinophil counts were increased in six of 13 patients; a relative peripheral eosinophilia was present in 10 of 13 patients. Serum IgE levels were elevated in all seven patients tested (range, 88 to 9050 IU). Histopathologic features included a folliculitis with eosinophils. Pathogenic bacteria were not consistently found by routine bacterial skin cultures, cultures of skin biopsy specimens, or histopathologic evaluation. CD4 counts were decreased in all of the 12 patients tested (less than 300 cells per cubic millimeter) and were below 250 cells per cubic millimeter in 10 patients. A clinical response was noted to astemizole, to ultraviolet light in the B range, and to topical clobetasol propionate. These observations demonstrate that HIV-associated eosinophilic folliculitis is a unique HIV-related cutaneous disorder that is characterized by a culture-negative, chronic, pruritic folliculitis and a characteristic histopathologic picture. Of special importance, because it is associated with CD4 counts of less than 250 to 300 cells per cubic millimeter, eosinophilic folliculitis appears to be an important clinical marker of HIV infection and, particularly, of patients at increased risk of developing opportunistic infections. We suggest that the term eosinophilic pustular folliculitis (Ofuji's disease), previously used to describe this dermatosis in HIV-infected patients, should be discarded.

Cerebral signal intensity abnormalities on T2-weighted MR images in HIV patients with highly active antiretroviral therapy: relationship with clinical parameters and interval changes.

PubMed

Hanning, Uta; Husstedt, Ingo W; Niederstadt, Thomas-Ulrich; Evers, Stefan; Heindel, Walter; Kloska, Stephan P

2011-09-01

The aim of this study was to assess the relationship between immune state and cerebral signal intensity abnormalities (SIAs) on T2-weighted magnetic resonance images in subjects with human immunodeficiency virus type 1 infection and highly active antiretroviral therapy. Thirty-two subjects underwent a total of 109 magnetic resonance studies. The presence of human immunodeficiency virus-associated neurocognitive disorder, categorized CD4(+) T lymphocyte count, and plasma viral load were assessed for relationship with the severity and interval change of SIAs for different anatomic locations of the brain. Subjects with multifocal patterns of SIAs had CD4(+) cell counts < 200 cells/μL in 66.0%, whereas subjects with diffuse patterns of SIAs had CD4(+) cell counts < 200 cells/μL in only 31.4% (P < .001). Subjects without SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 37.0%, whereas subjects with minor and moderate SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 78.3% and 80.0%, respectively (P < .005). The percentage of subjects with CD4(+) cell counts < 200 cells/μL was 85.7% when there were progressive periventricular SIA changes and 45.5% when periventricular SIA changes were stable in follow-up (P < .05). The presence and progression of cerebral SIAs on T2-weighted magnetic resonance images reflecting cerebral infection with human immunodeficiency virus are significantly related to impaired immune state as measured by CD4(+) cell count. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir

PubMed Central

Avalos, Claudia R.; Abreu, Celina M.; Queen, Suzanne E.; Li, Ming; Price, Sarah; Shirk, Erin N.; Engle, Elizabeth L.; Forsyth, Ellen; Bullock, Brandon T.; Mac Gabhann, Feilim; Wietgrefe, Stephen W.; Haase, Ashley T.; Zink, M. Christine; Mankowski, Joseph L.; Clements, Janice E.

2017-01-01

ABSTRACT A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. PMID:28811349

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

PubMed

Rumi, Maria Grazia; Di Marco, Vito; Colombo, Massimo

2018-05-01

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient: A Case Report.

PubMed

ten Berge, Josianne C E M; van Daele, Paul L A; Rothova, Aniki

2016-01-01

Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system.

Immunodeficiency-associated vaccine-derived poliovirus type 3 in infant, South Africa, 2011.

PubMed

Gumede, Nicksy; Muthambi, Vongani; Schoub, Barry D

2012-06-01

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome.

Postural reconfiguration and cycle-to-cycle variability in patients with work-related musculoskeletal disorders compared to healthy controls and in relation to pain emerging during a repetitive movement task.

PubMed

Longo, Alessia; Meulenbroek, Ruud; Haid, Thomas; Federolf, Peter

2018-05-01

Movement variability in sustained repetitive tasks is an important factor in the context of work-related musculoskeletal disorders. While a popular hypothesis suggests that movement variability can prevent overuse injuries, pain evolving during task execution may also cause variability. The aim of the current study was to investigate, first, differences in movement behavior between volunteers with and without work-related pain and, second, the influence of emerging pain on movement variability. Upper-body 3D kinematics were collected as 22 subjects with musculoskeletal disorders and 19 healthy volunteers performed a bimanual repetitive tapping task with a self-chosen and a given rhythm. Three subgroups were formed within the patient group according to the level of pain the participants experienced during the task. Principal component analysis was applied to 30 joint angle coordinates to characterize in a combined analysis the movement variability associated with reconfigurations of the volunteers' postures and the cycle-to-cycle variability that occurred during the execution of the task. Patients with no task-related pain showed lower cycle-to-cycle variability compared to healthy controls. Findings also indicated an increase in movement variability as pain emerged, manifesting both as frequent postural changes and large cycle-to-cycle variability. The findings suggested a relationship between work-related musculoskeletal disorders and movement variability but further investigation is needed on this issue. Additionally, the findings provided clear evidence that pain increased motor variability. Postural reconfigurations and cycle-to-cycle variability should be considered jointly when investigating movement variability and musculoskeletal disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Eruptive dysplastic nevi associated with human immunodeficiency virus infection.

PubMed

Duvic, M; Lowe, L; Rapini, R P; Rodriguez, S; Levy, M L

1989-03-01

The cutaneous manifestations of the acquired immunodeficiency syndrome include infections and neoplasms resulting from the immunodeficient state. Seven patients presenting with the symptom of new eruptive nevi with dysplastic histologic findings are described. These patients noted multiple new moles, which occurred in crops and in individuals without the dysplastic nevus syndrome (familial melanomas). This symptom occurred as the patients became symptomatic from their human immunodeficiency virus infection, developing acquired immunodeficiency syndrome or its related complex. Further confirmation and study of this phenomenon could lead to a better understanding of the pathogenesis of melanocytic dysplasia and its relationship to the immune system.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

PubMed

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

Personality, emotion-related variables, and media pressure predict eating disorders via disordered eating in Lebanese university students.

PubMed

Sanchez-Ruiz, Maria Jose; El-Jor, Claire; Abi Kharma, Joelle; Bassil, Maya; Zeeni, Nadine

2017-04-18

Disordered eating behaviors are on the rise among youth. The present study investigates psychosocial and weight-related variables as predictors of eating disorders (ED) through disordered eating (DE) dimensions (namely restrained, external, and emotional eating) in Lebanese university students. The sample consisted of 244 undergraduates (143 female) aged from 18 to 31 years (M = 20.06; SD = 1.67). Using path analysis, two statistical models were built separately with restrained and emotional eating as dependent variables, and all possible direct and indirect pathways were tested for mediating effects. The variables tested for were media influence, perfectionism, trait emotional intelligence, and the Big Five dimensions. In the first model, media pressure, self-control, and extraversion predicted eating disorders via emotional eating. In the second model, media pressure and perfectionism predicted eating disorders via restrained eating. Findings from this study provide an understanding of the dynamics between DE, ED, and key personality, emotion-related, and social factors in youth. Lastly, implications and recommendations for future studies are advanced.

Cognitive functioning and insight in schizophrenia and in schizoaffective disorder.

PubMed

Birindelli, Nadia; Montemagni, Cristiana; Crivelli, Barbara; Bava, Irene; Mancini, Irene; Rocca, Paola

2014-01-01

The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.

Profiles of drug addicts in relation to personality variables and disorders.

PubMed

Carou, María; Romero, Estrella; Luengo, Mª Ángeles

2016-10-07

In recent decades, research has identified a set of impulsive/disinhibited personality variables closely associated with drug addiction. As well as this, disorders linked with these variables, such as ADHD and personality disorders, are being closely studied in the field of drug addiction. Although much knowledge has been accumulated about the relation of these variables and disorders taken separately, less is known about how these constructs allow identify-specific profiles within the drug dependent population to be identified. This work, on the basis of data collected on a sample of drug addicts in treatment, analyzes how impulsiveness, sensation seeking, self-control, ADHD and personality disorders contribute to identifying specific profiles of addicts. Cluster analysis allowed two profiles to be outlined according to these personality and psychopathology characteristics. Self-control, impulsiveness, impulsive and antisocial personality disorders, as well as scores in ADHD, emerge as the variables that contribute more to profile differentiation. One of these profiles (56.1% of participants) with a high disinhibition pattern, is associated with severe indicators of consumption and criminal career patterns. These results allow us to emphasize the role of personality and impulsiveness-related disorders in the identification of distinctive profiles within the addict population, and suggest the need to generate treatment strategies adapted to personal/psychopathology configurations of drug addicts.

Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

2017-03-01

Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder

PubMed Central

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-01-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion: The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder. PMID:28050180

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder.

PubMed

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-10-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion : The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder.

Aicardi-Goutieres syndrome: from patients to genes and beyond.

PubMed

Chahwan, C; Chahwan, R

2012-05-01

Aicardi-Goutières syndrome (AGS) is a hereditary neurodegenerative disorder characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Although it was initially mistaken for intrauterine viral infections, AGS has now been genetically attributed to a lack of adequate processing of cellular nucleic acid debris, which culminates in the perpetual trigger of the innate and acquired immune responses. Although the exact mechanisms governing AGS are not fully understood, significant strides have been recently achieved in better characterizing the disorder and the molecular functions of the five known proteins found mutated in AGS. Studies have now uncovered that AGS is tightly linked with the predisposition to other autoimmune disorders such as familial chilblain lupus and systemic lupus erythematosus. Moreover, at least two of the proteins mutated in AGS, namely TREX1 and SAMHD1, also seem to have antagonistic roles in safeguarding humans from human immunodeficiency virus (HIV) infections. We hereby synthesize the current developments into the greater framework of AGS and suggest that a better understanding of AGS might help usher a better treatment not only for some autoimmune disorders but also possibly for patients suffering from HIV infections, too. © 2011 John Wiley & Sons A/S.

Deletion of Fanca or Fancd2 dysregulates Treg in mice

PubMed Central

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

2014-01-01

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques

PubMed Central

Grüner, Nico; Stambouli, Oumaima; Ross, R. Stefan

2015-01-01

The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resource-limited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen. PMID:25867233

Variable context Markov chains for HIV protease cleavage site prediction.

PubMed

Oğul, Hasan

2009-06-01

Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

[Refusal of care by a HIV-positive adolescent: role of the cross-cultural approach].

PubMed

Bouaziz, Nora; Titia Rizzi, Alice

The refusal of treatment is frequent in human immunodeficiency virus-positive adolescents. The clinical history of a teenage girl presenting severe immunodepression secondary to the virus, a depressive disorder and a refusal of treatment, illustrates the benefit of combined paediatric, child psychiatric and cross-cultural care as proposed by the Cochin-Paris Adolescent Centre. Working on the meaning of the refusal was a prerequisite for the construction of a care project forming part of a life project, as the psychopathological work could only begin once somatic care ensuring the patient's protection was in place. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Eosinophilic Pustular Folliculitis in Children after Stem Cell Transplantation: An Eruption Distinct from Graft-Versus-Host Disease.

PubMed

Theiler, Martin; Oza, Vikash S; Mathes, Erin F; Dvorak, Christopher C; McCalmont, Timothy H; Yeh, Iwei; Sidbury, Robert; Cordoro, Kelly M

2017-05-01

Eosinophilic pustular folliculitis (EPF) is a rare cutaneous disorder that typically occurs in three clinical contexts: men, individuals who are immunosuppressed or have human immunodeficiency virus, and infants. A fourth subtype occurring 2 to 3 months after hematopoietic stem cell transplantation (HSCT) has recently been described in several adults. We report two cases of EPF arising in children after HSCT. It is important to recognize this form of EPF after HSCT and differentiate it from graft-versus-host disease since it responds readily to topical steroids and appears to have an excellent prognosis. © 2017 Wiley Periodicals, Inc.

Drug treatment of HIV associated neuropsychiatric syndromes.

PubMed

Ayuso Mateos, J L; Singh, A N; Catalán, J

2000-04-01

Psychotropic drugs are frequently used to treat the wide range of neuropsychiatric syndromes that patients infected with the human immunodeficiency virus (HIV) may develop. In order to administer these agents properly, physicians should take into account, among other factors, that: the central nervous system (CNS) of these patients is often impaired; they tend to suffer from one or more physical disorders; and they may be taking various other medications. The present paper reviews the clinical features and the general guidelines for administering neuroleptics, antidepressants, psychostimulants, benzodiazepines, opiates, lithium and carbamazepine in this group of patients, based on the literature and the authors' own clinical experience.

[Skin symptoms associated with human immunodeficiency virus infection].

PubMed

Tamási, Béla; Marschalkó, Márta; Kárpáti, Sarolta

2015-01-04

The recently observed accelerated increase of human immunodeficiency virus infection in Hungary poses a major public concern for the healthcare system. Given the effective only but not the curative therapy, prevention should be emphasized. Current statistics estimate that about 50% of the infected persons are not aware of their human immunodeficiency virus-positivity. Thus, early diagnosis of the infection by serological screening and timely recognition of the disease-associated symptoms are crucial. The authors' intention is to facilitate early infection detection with this review on human immunodeficiency virus-associated skin symptoms, and highlight the significance of human immunodeficiency virus care in the everyday medical practice.

Heterogeneity in Neutralization Sensitivities of Viruses Comprising the Simian Immunodeficiency Virus SIVsmE660 Isolate and Vaccine Challenge Stock

PubMed Central

Lopker, Michael; Easlick, Juliet; Sterrett, Sarah; Decker, Julie M.; Barbian, Hannah; Learn, Gerald; Keele, Brandon F.; Robinson, James E.; Li, Hui; Hahn, Beatrice H.; Shaw, George M.

2013-01-01

The sooty mangabey-derived simian immunodeficiency virus (SIV) strain E660 (SIVsmE660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (NHP) model of human immunodeficiency virus type 1 (HIV-1) infection. Though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. Here, we utilize single-genome sequencing and infectivity assays to analyze the neutralization sensitivity of the uncloned SIVsmE660 isolate, individual viruses comprising the isolate, and transmitted/founder (T/F) viruses arising from low-dose mucosal inoculation of macaques with the isolate. We found that the SIVsmE660 isolate overall was highly sensitive to neutralization by SIV-infected macaque plasma samples (50% inhibitory concentration [IC50] < 10−5) and monoclonal antibodies targeting V3 (IC50 < 0.01 μg/ml), CD4-induced (IC50 < 0.1 μg/ml), CD4 binding site (IC50 ∼ 1 μg/ml), and V4 (IC50, ∼5 μg/ml) epitopes. In comparison, SIVmac251 and SIVmac239 were highly resistant to neutralization by these same antibodies. Differences in neutralization sensitivity between SIVsmE660 and SIVmac251/239 were not dependent on the cell type in which virus was produced or tested. These findings indicate that in comparison to SIVmac251/239 and primary HIV-1 viruses, SIVsmE660 generally exhibits substantially less masking of antigenically conserved Env epitopes. Interestingly, we identified a minor population of viruses (∼10%) in both the SIVsmE660 isolate and T/F viruses arising from it that were substantially more resistant (>1,000-fold) to antibody neutralization and another fraction (∼20%) that was intermediate in neutralization resistance. These findings may explain the variable natural history and variable protection afforded by heterologous Env-based vaccines in rhesus macaques challenged by high-dose versus low-dose SIVsmE660 inoculation regimens. PMID:23468494

Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS.

PubMed Central

Kodama, T; Mori, K; Kawahara, T; Ringler, D J; Desrosiers, R C

1993-01-01

One rhesus macaque displayed severe encephalomyelitis and another displayed severe enterocolitis following infection with molecularly cloned simian immunodeficiency virus (SIV) strain SIVmac239. Little or no free anti-SIV antibody developed in these two macaques, and they died relatively quickly (4 to 6 months) after infection. Manifestation of the tissue-specific disease in these macaques was associated with the emergence of variants with high replicative capacity for macrophages and primary infection of tissue macrophages. The nature of sequence variation in the central region (vif, vpr, and vpx), the env gene, and the nef long terminal repeat (LTR) region in brain, colon, and other tissues was examined to see whether specific genetic changes were associated with SIV replication in brain or gut. Sequence analysis revealed strong conservation of the intergenic central region, nef, and the LTR. However, analysis of env sequences in these two macaques and one other revealed significant, interesting patterns of sequence variation. (i) Changes in env that were found previously to contribute to the replicative ability of SIVmac for macrophages in culture were present in the tissues of these animals. (ii) The greatest variability was located in the regions between V1 and V2 and from "V3" through C3 in gp120, which are different in location from the variable regions observed previously in animals with strong antibody responses and long-term persistent infection. (iii) The predominant sequence change of D-->N at position 385 in C3 is most surprising, since this change in both SIV and human immunodeficiency virus type 1 has been associated with dramatically diminished affinity for CD4 and replication in vitro. (iv) The nature of sequence changes at some positions (146, 178, 345, 385, and "V3") suggests that viral replication in brain and gut may be facilitated by specific sequence changes in env in addition to those that impart a general ability to replicate well in macrophages. These results demonstrate that complex selective pressures, including immune responses and varying cell and tissue specificity, can influence the nature of sequence changes in env. Images PMID:8411355

Evaluating the Genetics of Common Variable Immunodeficiency: Monogenetic Model and Beyond.

PubMed

de Valles-Ibáñez, Guillem; Esteve-Solé, Ana; Piquer, Mònica; González-Navarro, E Azucena; Hernandez-Rodriguez, Jessica; Laayouni, Hafid; González-Roca, Eva; Plaza-Martin, Ana María; Deyà-Martínez, Ángela; Martín-Nalda, Andrea; Martínez-Gallo, Mónica; García-Prat, Marina; Del Pino-Molina, Lucía; Cuscó, Ivón; Codina-Solà, Marta; Batlle-Masó, Laura; Solís-Moruno, Manuel; Marquès-Bonet, Tomàs; Bosch, Elena; López-Granados, Eduardo; Aróstegui, Juan Ignacio; Soler-Palacín, Pere; Colobran, Roger; Yagüe, Jordi; Alsina, Laia; Juan, Manel; Casals, Ferran

2018-01-01

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis is made based on clinical and immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20% of cases of CVID have a known underlying genetic cause. We have analyzed whole-exome sequencing and copy number variants data of 36 children and adolescents diagnosed with CVID and healthy relatives to estimate the proportion of monogenic cases. We have replicated an association of CVID to p.C104R in TNFRSF13B and reported the second case of homozygous patient to date. Our results also identify five causative genetic variants in LRBA, CTLA4, NFKB1 , and PIK3R1 , as well as other very likely causative variants in PRKCD, MAPK8 , or DOCK8 among others. We experimentally validate the effect of the LRBA stop-gain mutation which abolishes protein production and downregulates the expression of CTLA4, and of the frameshift indel in CTLA4 producing expression downregulation of the protein. Our results indicate a monogenic origin of at least 15-24% of the CVID cases included in the study. The proportion of monogenic patients seems to be lower in CVID than in other PID that have also been analyzed by whole exome or targeted gene panels sequencing. Regardless of the exact proportion of CVID monogenic cases, other genetic models have to be considered for CVID. We propose that because of its prevalence and other features as intermediate penetrancies and phenotypic variation within families, CVID could fit with other more complex genetic scenarios. In particular, in this work, we explore the possibility of CVID being originated by an oligogenic model with the presence of heterozygous mutations in interacting proteins or by the accumulation of detrimental variants in particular immunological pathways, as well as perform association tests to detect association with rare genetic functional variation in the CVID cohort compared to healthy controls.

Genetics Home Reference: X-linked severe combined immunodeficiency

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked SCID X-linked severe combined immunodeficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked severe combined immunodeficiency (SCID) is an inherited ...

Unmet needs among men with human immunodeficiency virus in community mental health care: a cross-sectional study.

PubMed

Durbin, Anna; Sirotich, Frank; Antoniou, Tony; Roesslein, Kay; Durbin, Janet; Lunsky, Yona

2016-07-01

While community-based mental health services play an important role in caring for persons with HIV (human immunodeficiency virus) and co-existing mental health disorders, the extent to which their support needs are addressed in this setting is unknown. Accordingly, we examined if HIV infection was associated with unmet support needs among men living with and without HIV receiving community mental health care. This cross-sectional study examined 215 men (135 living with HIV and 80 without HIV) receiving case management services in urban Ontario. Using the Camberwell Assessment of Need, we ascertained the prevalence of support needs in 13 domains grouped into three clusters: Basic needs (accommodation, food, benefits, and money management); self-care/functional needs (daytime activities, self-care, and looking after the home); and health/safety needs (physical, psychological distress, psychotic symptoms, safety to self, and safety to others). We used generalized estimating equations with a logit link to examine the association between HIV and unmet need in each domain. Compared to HIV-negative men, men with HIV were more likely to have mood and concurrent disorders, and intellectual and developmental disabilities. Following multivariable analyses, men with HIV had greater unmet needs related to food (odds ratio + 95% confidence interval: 9.36 (4.03, 21.75), p < 0.001); money (OR: 1.90 (1.04, 3.47), p = 0.036) [basic need domains]; psychological distress (OR: 2.39 (1.68, 3.41), p < 0.001); drug use (OR: 5.10 (2.16, 12.08) p < 0.001); and safety to self (OR: 3.35 (1.51, 7.52), p < 0.003) [health and safety domains]. Despite living in a setting with universal health insurance, men with HIV receiving community mental health support had greater unmet need in basic and health domains than HIV-negative men receiving such support. Further research is required to develop and evaluate interventions to best support community-dwelling persons with HIV and mental health disorders.

Harm reduction in the USA: the research perspective and an archive to David Purchase.

PubMed

Des Jarlais, Don C

2017-07-26

The history of harm reduction in the USA has led to the development of some of the most important methods for treating persons for drug use disorders, such as methadone and buprenorphine for opiate use disorder. However, there has been fierce political resistance to implementation and scale-up of harm reduction in the USA. This resistance is rooted in historical demonization of particular psychoactive drugs that were associated with stigmatized racial/ethnic groups.With the discovery of acquired immunodeficiency syndrome (AIDS) in 1981, harm reduction became important not only for treating substance use disorders, but for reducing transmission of blood-borne infection. However, within the context of the crack cocaine epidemic in the 1980s, it was very difficult to implement any programs that appeared to "condone" drug use.It was not until the late 1980s that syringe exchange programs began at the state and local level in the USA. With funding primarily from state and local governments and the support of the North American Syringe Exchange Network (NASEN), there are now approximately 200 programs for syringe exchange in the USA. Research has shown that these programs have been extremely effective in reducing human immunodeficiency virus (HIV) transmission among persons who inject drugs (PWID). The programs in the USA also offer many additional services for drug users, including condom distribution, referrals to substance abuse treatment, HIV, hepatitis C virus (HCV), hepatitis B virus (HBV) counseling and testing, overdose education and naloxone distribution to reverse for overdose.Currently, the USA is experiencing an opioid/heroin epidemic, with significant increases in overdose deaths among drug users. Much of this epidemic is occurring in suburban and rural of the country without harm reduction services. The current challenges for harm reduction and harm reduction research involve expansion of services to suburban and rural areas and implementation science on how to effectively and efficiently address HCV transmission and overdose. Most importantly, continued research efforts are needed to reduce the stigma of psychoactive drug use. While political opposition continues, harm reduction activists and researchers have developed a highly effective partnership based on a common core values.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

PubMed Central

Marsh, Angie K.; Huibner, Sanja; Shahabi, Kamnoosh; Liu, Cindy; Contente, Tania; Nagelkerke, Nico J. D.; Kovacs, Colin; Benko, Erika; Price, Lance; MacDonald, Kelly S.; Kaul, Rupert

2017-01-01

Abstract Background. This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. Methods. Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. Results. Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels. Conclusions. Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway. PMID:28534034

Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding.

PubMed

Ceballos, Ana; Andreani, Guadalupe; Ripamonti, Chiara; Dilernia, Dario; Mendez, Ramiro; Rabinovich, Roberto D; Cárdenas, Patricia Coll; Zala, Carlos; Cahn, Pedro; Scarlatti, Gabriella; Martínez Peralta, Liliana

2008-11-01

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

Predictors of reported condom use in central Harlem youth as conceptualized by the health belief model.

PubMed

Laraque, D; McLean, D E; Brown-Peterside, P; Ashton, D; Diamond, B

1997-11-01

To examine the relationship of reported condom use to specific sociodemographics, psychosocial variables, and perceptions of and motivations for condom use as conceptualized by the Health Belief Model. This study performed a cross-sectional survey of 557 adolescents enrolled in a hospital-based pregnancy prevention program in an urban community hospital (Harlem Hospital). Multiple logistic regression analysis examined the combined relationship of the significant psychosocial variables to consistent condom use. Males were less likely than females to report teen-parent conflict and depression and more likely to report support for birth control, participation in community activities, and favorable attitudes toward delaying parenthood. Consistent with the Health Belief Model adjusting for age, the strongest predictors of consistent condom use were partner preference for condoms, perceived benefit of avoidance of pregnancy, male gender, and support for birth control (usually by a parent). The data on this urban, predominantly African-American sample of adolescents suggest the importance of the influences on specific motivations to use protection--that is, the wish to avoid pregnancy, human immunodeficiency virus/acquired immunodeficiency syndrome, and sexually transmitted diseases, although the mechanisms are still unclear. In addition, gender and the modifying effects of parental and partner support of the use of protection strongly influence the reported use of condoms by adolescents. These factors (in addition to psychosocial factors such as depression) may be important in planning interventions to increase condom use by sexually active teens.

Serum killing of Ureaplasma parvum shows serovar-determined susceptibility for normal individuals and common variable immuno-deficiency patients.

PubMed

Beeton, Michael L; Daha, Mohamed R; El-Shanawany, Tariq; Jolles, Stephen R; Kotecha, Sailesh; Spiller, O Brad

2012-02-01

Many Gram-negative bacteria, unlike Gram-positive, are directly lysed by complement. Ureaplasma can cause septic arthritis and meningitis in immunocompromised individuals and induce premature birth. Ureaplasma has no cell wall, cannot be Gram-stain classified and its serum susceptibility is unknown. Survival of Ureaplasma serovars (SV) 1, 3, 6 and 14 (collectively Ureaplasma parvum) were measured following incubation with normal or immunoglobulin-deficient patient serum (relative to heat-inactivated controls). Blocking monoclonal anti-C1q antibody and depletion of calcium, immunoglobulins, or lectins were used to determine the complement pathway responsible for killing. Eighty-three percent of normal sera killed SV1, 67% killed SV6 and 25% killed SV14; greater killing correlating to strong immunoblot identification of anti-Ureaplasma antibodies; killing was abrogated following ProteinA removal of IgG1. All normal sera killed SV3 in a C1q-dependent fashion, irrespective of immunoblot identification of anti-Ureaplasma antibodies; SV3 killing was unaffected by total IgG removal by ProteinG, where complement activity was retained. Only one of four common variable immunodeficient (CVID) patient sera failed to kill SV3, despite profound IgM and IgG deficiency for all; however, killing of SV3 and SV1 was restored with therapeutic intravenous immunoglobulin therapy. Only the classical complement pathway mediated Ureaplasma-cidal activity, sometimes in the absence of observable immunoblot reactive bands. Copyright © 2011 Elsevier GmbH. All rights reserved.

A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.

PubMed Central

Levi, M; Sällberg, M; Rudén, U; Herlyn, D; Maruyama, H; Wigzell, H; Marks, J; Wahren, B

1993-01-01

A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons. PMID:7685100

Determination of Coreceptor Usage of Human Immunodeficiency Virus Type 1 from Patient Plasma Samples by Using a Recombinant Phenotypic Assay

PubMed Central

Trouplin, Virginie; Salvatori, Francesca; Cappello, Fanny; Obry, Veronique; Brelot, Anne; Heveker, Nikolaus; Alizon, Marc; Scarlatti, Gabriella; Clavel, François; Mammano, Fabrizio

2001-01-01

We developed a recombinant virus technique to determine the coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from plasma samples, the source expected to represent the most actively replicating virus population in infected subjects. This method is not subject to selective bias associated with virus isolation in culture, a step required for conventional tropism determination procedures. The addition of a simple subcloning step allowed semiquantitative evaluation of virus populations with a different coreceptor (CCR5 or CXCR4) usage specificity present in each plasma sample. This procedure detected mixtures of CCR5- and CXCR4-exclusive virus populations as well as dualtropic viral variants, in variable proportions. Sequence analysis of dualtropic clones indicated that changes in the V3 loop are necessary for the use of CXCR4 as a coreceptor, but the overall context of the V1-V3 region is important to preserve the capacity to use CCR5. This convenient technique can greatly assist the study of virus evolution and compartmentalization in infected individuals. PMID:11119595

Spiritual activities as a resistance resource for women with human immunodeficiency virus.

PubMed

Sowell, R; Moneyham, L; Hennessy, M; Guillory, J; Demi, A; Seals, B

2000-01-01

Few studies have investigated the role that spiritual activities play in the adaptational outcomes of women with human immunodeficiency virus (HIV) disease. To examine the role of spiritual activities as a resource that may reduce the negative effects of disease-related stressors on the adaptational outcomes in HIV-infected women. A theoretically based causal model was tested to examine the role of spiritual activities as a moderator of the impact of HIV-related stressors (functional impairment, work impairment, and HIV-related symptoms) on two stress-related adaptational outcomes (emotional distress and quality of life), using a clinic-based sample of 184 HIV-positive women. Findings indicated that as spiritual activities increased, emotional distress decreased even when adjustments were made for HIV-related stressors. A positive relationship between spiritual activities and quality of life was found, which approached significance. Findings showed that HIV-related stressors have a significant negative effect on both emotional distress and quality of life. The findings support the hypothesis that spiritual activities are an important psychological resource accounting for individual variability in adjustment to the stressors associated with HIV disease.

The Dynamics of Self-Esteem in Cognitive Therapy for Avoidant and Obsessive-Compulsive Personality Disorders: An Adaptive Role of Self-Esteem Variability?

PubMed Central

Cummings, Jorden A.; Hayes, Adele M.; Cardaciotto, LeeAnn; Newman, Cory F.

2011-01-01

Self-esteem variability is often associated with poor functioning. However, in disorders with entrenched negative views of self and in a context designed to challenge those views, variable self-esteem might represent a marker of change. We examined self-esteem variability in a sample of 27 patients with Avoidant and Obsessive-Compulsive Personality Disorders who received Cognitive Therapy (CT). A therapy coding system was used to rate patients’ positive and negative views of self expressed in the first ten sessions of a 52-week treatment. Ratings of negative (reverse scored) and positive view of self were summed to create a composite score for each session. Self-esteem variability was calculated as the standard deviation of self-esteem scores across sessions. More self-esteem variability predicted more improvement in personality disorder and depression symptoms at the end of treatment, beyond baseline and average self-esteem. Early variability in self-esteem, in this population and context, appeared to be a marker of therapeutic change. PMID:22923855

Human immunodeficiency virus infection and pneumothorax

PubMed Central

Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

2014-01-01

Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

Differences in clinical intrusive thoughts between obsessive-compulsive disorder, generalized anxiety disorder, and hypochondria.

PubMed

Romero-Sanchiz, Pablo; Nogueira-Arjona, Raquel; Godoy-Ávila, Antonio; Gavino-Lázaro, Aurora; Freeston, Mark H

2017-11-01

Differences and similarities between intrusive thoughts typical of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis are relevant for their differential diagnosis, formulation, and psychological treatment. Previous research in non-clinical samples pointed out the relevance of some process variables, such as responsibility, guilt, or neutralization strategies. This research is aimed to investigate the differences and similarities between clinical obsessions, worries, and illness intrusions in some of these process variables. A second aim is to identify models based on these variables that could reliably differentiate between them. Three groups of patients with obsessive-compulsive disorder (n = 35; 60% women, mean age 38.57), generalized anxiety disorder (n = 36; 61.1% women, mean age 41.50), and hypochondriasis (n = 34; 70.6% women, mean age 31.59) were evaluated using the Cognitive Intrusions Questionnaire-Transdiagnostic Version (Romero-Sanchiz, Nogueira-Arjona, Godoy-Ávila, Gavino-Lázaro, & Freeston, ). The results showed that some appraisals (e.g., responsibility or egodystonicity), emotions (e.g., guilt or insecurity), neutralization strategies, and other variables (e.g., verbal content or trigger from body sensation) are relevant for the discrimination between obsessions, worries, and illness intrusions. The results also showed 3 stable models based on these variables for the discrimination between these thoughts. The implication of these results in the diagnosis, formulation, and psychological treatment of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis is discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Clinical Spectrum, Etiology, and Outcome of Neurological Disorders in the Rural Hospital of Mosango, the Democratic Republic of Congo.

PubMed

Mukendi, Deby; Lilo Kalo, Jean-Roger; Mpanya, Alain; Minikulu, Luigi; Kayembe, Tharcisse; Lutumba, Pascal; Barbé, Barbara; Gillet, Philippe; Jacobs, Jan; Van Loen, Harry; Yansouni, Cédric P; Chappuis, François; Ravinetto, Raffaella; Verdonck, Kristien; Boelaert, Marleen; Winkler, Andrea S; Bottieau, Emmanuel

2017-11-01

There is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children > 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3-6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.

Corpus Callosum Size, Reaction Time Speed and Variability in Mild Cognitive Disorders and in a Normative Sample

ERIC Educational Resources Information Center

Anstey, Kaarin J.; Mack, Holly A.; Christensen, Helen; Li, Shu-Chen; Reglade-Meslin, Chantal; Maller, Jerome; Kumar, Rajeev; Dear, Keith; Easteal, Simon; Sachdev, Perminder

2007-01-01

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and…

Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

PubMed

Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

2016-08-01

SEE MATTAR ET AL DOI101093/AWW151 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correlates Associated with Unipolar Depressive Disorders in a Latino Population

PubMed Central

Correa-Fernandez, Virmarie; Carrión-Baralt, José R.; Alegría, Margarita; Albizu-García, Carmen E.

2014-01-01

Background This study reports the comparison and associations of demographic, clinical, and psychosocial correlates with three unipolar depressive disorders: dysthymia (DYS), major depression (MD), and double depression (DD), and examines to which extent these variables predict the disorders. Sampling and Method Previously collected data from 563 adults from a community in Puerto Rico were analyzed. One hundred and thirty individuals with DYS, 260 with MD, and 173 with DD were compared by demographic variables, psychiatric and physical comorbidity, familial psychopathology, psychosocial stressors, functional impairment, self-reliance, problem recognition and formal use of mental health services. Multinomial regression was used to assess the association of the predictor variables with each of the three disorders. Results Similarities outweighed the discrepancies between disorders. The main differences observed were between MD and DD, while DYS shared common characteristics with both MD and DD. After other variables were controlled, anxiety, functional impairment, and problem recognition most strongly predicted a DD diagnosis while age predicted a DYS diagnosis. Conclusion MD, DYS, and DD are not completely different disorders but they do differ in key aspects that might be relevant for nosology, research, and practice. A dimensional system that incorporates specific categories of disorders would better reflect the different manifestations of unipolar depressive disorders. PMID:23006435

The Role of Faith-Based Organizations in the Education, Support, and Services for Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

PubMed

Stephens, Teresa M

2018-03-01

Faith-based organizations are in a unique position to provide resilience-enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many persons living with human immunodeficiency virus/AIDS report having a strong faith or religious affiliation, with a large percentage attending church services on a regular basis. Faith-based organizations can use these factors to reach out to these individuals and effectively promote health, well-being, education, and support. Faith-based organizations can contribute to the reduction of stigma and isolation for persons living with human immunodeficiency virus/AIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

Condensation with two constraints and disorder

NASA Astrophysics Data System (ADS)

Barré, J.; Mangeolle, L.

2018-04-01

We consider a set of positive random variables obeying two additive constraints, a linear and a quadratic one; these constraints mimic the conservation laws of a dynamical system. In the simplest setting, without disorder, it is known that such a system may undergo a ‘condensation’ transition, whereby one random variable becomes much larger than the others; this transition has been related to the spontaneous appearance of non linear localized excitations in certain nonlinear chains, called breathers. Motivated by the study of breathers in a disordered discrete nonlinear Schrödinger equation, we study different instances of this problem in presence of a quenched disorder. Unless the disorder is too strong, the phase diagram looks like the one without disorder, with a transition separating a fluid phase, where all variables have the same order of magnitude, and a condensed phase, where one variable is much larger than the others. We then show that the condensed phase exhibits various degrees of ‘intermediate symmetry breaking’: the site hosting the condensate is chosen neither uniformly at random, nor is it fixed by the disorder realization. Throughout the article, our heuristic arguments are complemented with direct Monte Carlo simulations.

[Association between the viruses of the acquired immunodeficiency syndrome and the hepatitis C virus among young blood donors in Kinshasa: Retrospective analysis of 10 years].

PubMed

Sumbu, B M M; Longo-Mbenza, B; Ahuka-Mundeke, S; Muwonga, J M; Mvumbi-Lelo, G; Maphana, H M; Kayembe Nzongola-Nkasu, D; Kalumbu, F M

2018-02-01

The screening of anti-Human Immunodeficiency Virus antibodies is mandatory in every blood donor admitted to the Blood Bank of Kinshasa University Clinics since 1984. However, no compiled data are available to date. The objective of this study was to establish the trend, prevalence, viral co-infections, and determinants of Human Immunodeficiency anti-Virus serology in blood donors admitted between 2003-2006 and 2008-2013. A retrospective analysis was carried out at University Kinshasa Clinics, using blood donors' records during 2003-2006 and 2008-2013. The prevalence of the human immunodeficiency virus per year, age, sex and type of blood donors were estimated. Independent predictors of human immunodeficiency virus seropositivity were also identified. Out of 26,341 blood donors, 2.2% (n=576/26,341) were seropositive for Human Immunodeficiency Virus. Age<25 years (OR=1.7; 95% CI: 1.4-2; P<0.0001) and Hepatitis C virus seropositivity (OR=3; 95% CI; 1.8-4.9; P<0.001) emerged as independent predictors of Human Immunodeficiency Virus seropositivity. This study shows a strong association between the Human Immunodeficiency Virus and hepatitis C and younger age respectively. Further studies are needed to ensure safety of Blood donation in Democratic Republic of Congo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mental capacity, diagnosis and insight in psychiatric in-patients: a cross-sectional study.

PubMed

Owen, G S; David, A S; Richardson, G; Szmukler, G; Hayward, P; Hotopf, M

2009-08-01

Mental capacity is now a core part of UK mental health law and clinicians will increasingly be expected to assess it. Because it is a legal concept there is a need to clarify associations with variables that clinicians are more familiar with, especially insight. In this cross-sectional study we recruited consecutive psychiatric admissions to the Maudsley Hospital, London. We carried out structured assessments of decision making using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), resulting in a clinical judgement about capacity status. We analysed associations with a range of sociodemographic and clinical variables, including insight score on the Expanded Schedule for the Assessment of Insight (SAI-E). The same variables were compared in an analysis stratified according to diagnostic group: psychotic disorders/bipolar affective disorder (BPAD)/non-psychotic disorders. Psychotic disorders and manic episodes of BPAD are most strongly associated with incapacity. In such patients, insight is the best discriminator of capacity status. In patients with non-psychotic disorders, insight is less strongly associated with capacity; in this group depressed mood discriminates capacity status whereas it does not in psychotic disorders. Cognitive performance does not discriminate capacity status in patients with psychotic disorders. Mental capacity has complex relationships with psychopathological variables, and these relationships are different according to diagnostic group. Insight is the best discriminator of capacity status in psychotic disorders and BPAD but not in non-psychotic disorders.

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

PubMed

Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

2013-02-01

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

PubMed Central

Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F.; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S. Munir; Fenizia, Claudio; Lifson, Jeffrey D.; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David

2013-01-01

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8+ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4+ and CD8+ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of α4β7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. PMID:23175374

Statistically Characterizing Intra- and Inter-Individual Variability in Children with Developmental Coordination Disorder

ERIC Educational Resources Information Center

King, Bradley R.; Harring, Jeffrey R.; Oliveira, Marcio A.; Clark, Jane E.

2011-01-01

Previous research investigating children with Developmental Coordination Disorder (DCD) has consistently reported increased intra- and inter-individual variability during motor skill performance. Statistically characterizing this variability is not only critical for the analysis and interpretation of behavioral data, but also may facilitate our…

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

MedlinePlus

... Share: Email Facebook Twitter Home Health Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ... Javascript to view the expand/collapse boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ...

Capturing public interest toward new tools for controlling human immunodeficiency virus (HIV) infection exploiting data from Google Trends.

PubMed

Mahroum, Naim; Bragazzi, Nicola Luigi; Brigo, Francesco; Waknin, Roy; Sharif, Kassem; Mahagna, Hussein; Amital, Howard; Watad, Abdulla

2018-04-01

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.

Temporary stages and motivational variables: Two complementary perspectives in the help-seeking process for mental disorders.

PubMed

Del Valle Del Valle, Gema; Carrió, Carmen; Belloch, Amparo

2017-10-09

Help-seeking for mental disorders is a complex process, which includes different temporary stages, and in which the motivational variables play an especially relevant role. However, there is a lack of instruments to evaluate in depth both the temporary and motivational variables involved in the help-seeking process. This study aims to analyse in detail these two sets of variables, using a specific instrument designed for the purpose, to gain a better understanding of the process of treatment seeking. A total of 152 patients seeking treatment in mental health outpatient clinics of the NHS were individually interviewed: 71 had Obsessive-Compulsive Disorder, 21 had Agoraphobia, 18 had Major Depressive Disorder), 20 had Anorexia Nervosa, and 22 had Cocaine Dependence. The patients completed a structured interview assessing the help-seeking process. Disorder severity and quality of life was also assessed. The patients with agoraphobia and with major depression took significantly less time in recognising their mental health symptoms. Similarly, patients with major depression were faster in seeking professional help. Motivational variables were grouped in 3 sets: motivators for seeking treatment, related to the negative impact of symptoms on mood and to loss of control over symptoms; motivators for delaying treatment, related to minimisation of the disorder; and stigma-associated variables. The results support the importance of considering the different motivational variables involved in the several stages of the help-seeking process. The interview designed to that end has shown its usefulness in this endeavour. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Ecto-5′-Nucleotidase Activity in Human T Cell Subsets. DECREASED NUMBERS OF ECTO-5′-NUCLEOTIDASE POSITIVE CELLS FROM BOTH OKT4+ AND OKT8+ CELLS IN PATIENTS WITH HYPOGAMMAGLOBULINEMIA

PubMed Central

Thompson, Linda F.; Saxon, Andrew; O'Connor, Richard D.; Fox, Robert I.

1983-01-01

T lymphocytes from control subjects were separated into subsets using monoclonal antibodies of the OKT series and complement lysis and analyzed for ecto-5′-nucleotidase activity both by quantitative radiochemical assay and a histochemical stain. T cells from 15 control subjects contained 54±4% OKT4+ (helper/inducer) cells and 32±3% OKT8+ (cytotoxic/suppressor) cells. Total T cell ecto-5′-nucleotidase activity was 10.9±2.1 nmol/h per 106 cells with 25±7% positive by histochemical stain. Ecto-5′-nucleotidase activity in OKT4-enriched populations was 5.43±1.8 nmol/h per 106 cells with 14±2% positive by histochemical stain; that in OKT8-enriched populations was 17.1±5.9 nmol/h per 106 cells with 35±8% positive by histochemical stain. Two of four patients with congenital agammaglobulinemia and four of seven patients with common variable immunodeficiency had decreased proportions of OKT4+ T cells with corresponding increases in the proportions of OKT8+ T cells (OKT4/OKT8 = 0.60 to 1.0 as compared with 1.7±0.2 for control subjects). All four patients with congenital agammaglobulinemia, and three of seven patients with common variable immunodeficiency also had low T cell ecto-5′-nucleotidase activity (<5.5 nmol/h per 106 cells). Ecto-5′-nucleotidase activity in OKT4- enriched populations isolated from four patients with low total T cell activity was 2.85±0.90 nmol/h per 106 cells with 10±4% positive by histochemical stain; that in OKT8-enriched populations was 6.82±1.7 nmol/h per 106 cells with 7.5±3% positive by histochemical stain. Thus, the number of ecto-5′-nucleotidase positive cells is decreased, especially in the OKT8+ subpopulation, and the low total T cell ecto-5′-nucleotidase activity seen in these patients is due to fewer positive cells rather than to substantially less activity per cell. Our data indicate that ecto-5′-nucleotidase activity defines two subpopulations of T lymphocytes (ecto-5′-nucleotidase positive and negative), the proportions of which are markedly altered in many patients with hypogammaglobulinemia. In preliminary studies with seven patients, increased numbers of ecto-5′-nucleotidase negative T cells appeared to correlate with increased suppressor T cell activity toward in vitro immunoglobulin synthesis. Therefore, ecto-5′-nucleotidase may be a useful cell surface marker in the study of imbalances of regulatory T cell subsets in patients with antibody synthesis disorders. PMID:6300192

Consanguinity and primary immunodeficiencies.

PubMed

Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima

2014-01-01

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.

Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia

PubMed Central

Boisson, Bertrand; Laplantine, Emmanuel; Dobbs, Kerry; Cobat, Aurélie; Tarantino, Nadine; Hazen, Melissa; Lidov, Hart G.W.; Hopkins, Gregory; Du, Likun; Belkadi, Aziz; Chrabieh, Maya; Itan, Yuval; Picard, Capucine; Fournet, Jean-Christophe; Eibel, Hermann; Tsitsikov, Erdyni; Pai, Sung-Yun; Abel, Laurent; Al-Herz, Waleed; Israel, Alain

2015-01-01

Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-κB activation are impaired in the patient’s fibroblasts stimulated by IL-1β or TNF. In contrast, the patient’s monocytes respond to IL-1β more vigorously than control monocytes. However, the activation and differentiation of the patient’s B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells. PMID:26008899

Epstein–Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency

PubMed Central

Carpier, Jean-Marie; Lucas, Carrie L.

2018-01-01

Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID) is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein–Barr virus (EBV) infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility. PMID:29387064

[Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy].

PubMed

Vázquez, C; Reyes, R; Alcaraz, F; Balsa, J A; Botella-Carretero, J I

2006-01-01

Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.

PubMed

Leveque, Lucie; Hodgson, Samantha; Peyton, Stephen; Koyama, Motoko; MacDonald, Kelli P A; Khosrotehrani, Kiarash

2014-05-01

The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

The Soriano Award Lecture. Emerging infections of the nervous system.

PubMed

Johnson, R T

1994-06-01

The epidemic of acquired immunodeficiency disease [AIDS] has focused interest on the origins of "new" infectious agents. Great plagues are well known from the distant past, but a number of novel diseases affecting the nervous system infections have emerged in recent years. The causes of such new disorders are diverse: whereas rapid mutations of microbes allow the evolution of truly novel agents, the appearance of new diseases is more often due to changes in human or vector populations or changes in societal mores that result in dissemination of preexistent microbes. Examples of recently emerging infections that involve the nervous system include the enterovirus 70 epidemics with poliomyelitis-like disease, the appearance of California virus encephalitis in the midwestern United States, the rapid spread of Lyme disease with its many neurological complications in the eastern United States, and the outbreak of bovine spongiform encephalopathy in the United Kingdom, in addition to the devastating epidemic of human immunodeficiency virus (HIV), which will cause nervous system disease in over half of those infected. As the world population increases and modern transportation brings us closer into a "global village" more new agents will emerge and more will be sustained. Knowledge of the molecular biology and ecology of the agents and awareness of how our actions can alter their behavior are our best defense.

2017 HIV Medicine Association of Infectious Diseases Society of America Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With Human Immunodeficiency Virus.

PubMed

Bruce, R Douglas; Merlin, Jessica; Lum, Paula J; Ahmed, Ebtesam; Alexander, Carla; Corbett, Amanda H; Foley, Kathleen; Leonard, Kate; Treisman, Glenn Jordan; Selwyn, Peter

2017-10-30

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Type I Interferon Responses by HIV-1 Infection: Association with Disease Progression and Control.

PubMed

Soper, Andrew; Kimura, Izumi; Nagaoka, Shumpei; Konno, Yoriyuki; Yamamoto, Keisuke; Koyanagi, Yoshio; Sato, Kei

2017-01-01

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome and its infection leads to the onset of several disorders such as the depletion of peripheral CD4 + T cells and immune activation. HIV-1 is recognized by innate immune sensors that then trigger the production of type I interferons (IFN-Is). IFN-Is are well-known cytokines eliciting broad anti-viral effects by inducing the expression of anti-viral genes called interferon-stimulated genes (ISGs). Extensive in vitro studies using cell culture systems have elucidated that certain ISGs such as APOBEC3G, tetherin, SAM domain and HD domain-containing protein 1, MX dynamin-like GTPase 2, guanylate-binding protein 5, and schlafen 11 exert robust anti-HIV-1 activity, suggesting that IFN-I responses triggered by HIV-1 infection are detrimental for viral replication and spread. However, recent studies using animal models have demonstrated that at both the acute and chronic phase of infection, the role of IFN-Is produced by HIV or SIV infection in viral replication, spread, and pathogenesis, may not be that straightforward. In this review, we describe the pluses and minuses of HIV-1 infection stimulated IFN-I responses on viral replication and pathogenesis, and further discuss the possibility for therapeutic approaches.

Gene correction of induced pluripotent stem cells derived from a murine model of X-linked chronic granulomatous disorder.

PubMed

Mukherjee, Sayandip; Thrasher, Adrian J

2014-01-01

Gene therapy presents an attractive alternative to allogeneic haematopoietic stem cell transplantation (HSCT) for treating patients suffering from primary immunodeficiency disorder (PID). The conceptual advantage of gene correcting a patient's autologous HSCs lies in minimizing or completely avoiding immunological complications arising from allogeneic transplantation while conferring the same benefits of immune reconstitution upon long-term engraftment. Clinical trials targeting X-linked chronic granulomatous disorder (X-CGD) have shown promising results in this context. However, long-term clinical benefits in these patients have been limited by issues of poor engraftment of gene-transduced cells coupled with transgene silencing and vector induced clonal proliferation. Novel vectors incorporating safety features such as self-inactivating (SIN) mutations in the long terminal repeats (LTRs) along with synthetic promoters driving lineage-restricted sustainable expression of the gp91phox transgene are expected to resolve the current pitfalls and require rigorous preclinical testing. In this chapter, we have outlined a protocol in which X-CGD mouse model derived induced pluripotent stem cells (iPSCs) have been utilized to develop a platform for investigating the efficacy and safety profiles of novel vectors prior to clinical evaluation.

Rapid Detection of Dendritic Cell and Monocyte Disorders Using CD4 as a Lineage Marker of the Human Peripheral Blood Antigen-Presenting Cell Compartment

PubMed Central

Jardine, Laura; Barge, Dawn; Ames-Draycott, Ashley; Pagan, Sarah; Cookson, Sharon; Spickett, Gavin; Haniffa, Muzlifah; Collin, Matthew; Bigley, Venetia

2013-01-01

Dendritic cells (DCs) and monocytes are critical regulators and effectors of innate and adaptive immune responses. Monocyte expansion has been described in many pathological states while monocyte and DC deficiency syndromes are relatively recent additions to the catalog of human primary immunodeficiency disorders. Clinically applicable screening tests to diagnose and monitor these conditions are lacking. Conventional strategies for identifying human DCs and monocytes have been based on the use of a lineage gate to exclude lymphocytes, thus preventing simultaneous detection of DCs, monocytes, and lymphocyte subsets. Here we demonstrate that CD4 is a reliable lineage marker for the human peripheral blood antigen-presenting cell compartment that can be used to identify DCs and monocytes in parallel with lymphocytes. Based on this principle, simple modification of a standard lymphocyte phenotyping assay permits simultaneous enumeration of four lymphocyte and five DC/monocyte populations from a single sample. This approach is applicable to clinical samples and facilitates the diagnosis of DC and monocyte disorders in a wide range of clinical settings, including genetic deficiency, neoplasia, and inflammation. PMID:24416034

Benjamin P. Flower (1962-2012)

NASA Astrophysics Data System (ADS)

Hastings, David W.; Shevenell, Amelia E.; Kennett, James P.

2012-10-01

Benjamin P. Flower, a gifted paleoceanographer and marine geologist, supportive colleague, and dedicated educator at the University of South Florida (USF) College of Marine Science (CMS) passed away on 1 July 2012 from complications related to a rare genetic immune dysfunction, Common Variable Immunodeficiency. He was 49 years old. During his brief illness, Ben's love of life and boundless high spirits were an inspiration to his family, friends, and colleagues. He exhibited remarkable courage and kept his sense of humor in face of adversity. Ben's intellectualism and enduring love of science remained intact, even in his last hours.

An unexpected diagnosis of human immunodeficiency virus-2 infection in an overseas visitor: a case report.

PubMed

Sohail, Asma; Van Leer, Lyndal; Holmes, Natasha

2017-03-04

Human immunodeficiency virus 2 infection is endemic in West Africa but is also found in parts of Europe, North and South America, and India where it is thought to have been introduced secondary to migration and commercial trade ties. It is less common than Human immunodeficiency virus 1, with differences in pathogenicity, lower rates of transmission, longer asymptomatic period and slower progression to acquired immunodeficiency syndrome. Human immunodeficiency virus 2 is also associated with diagnostic challenges given the lack of commercially available diagnostic tests, and management challenges given intrinsic resistance to many anti-retroviral therapies. We describe a case of a 65 year old South Indian female, visiting her family in Australia, who presented with weight loss, pancytopaenia and generalised lymphadenopathy on a background of newly diagnosed congestive cardiac failure. Multiple investigations were performed to elucidate the cause of her presentation, with the eventual unexpected diagnosis of human immunodeficiency virus 2. She was commenced on anti-retroviral treatment and made a remarkable recovery. We describe the challenges associated with diagnosis of human immunodeficiency virus 2 due to lack of commercially available diagnostics, as well as the treatment and management challenges including the fact that human immunodeficiency virus 2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors. Human immunodeficiency virus 2 infection should be considered in patients who present with symptoms and signs that do not point towards a clear diagnosis, such as unexplained pancytopaenia or lymphadenopathy, and who have risk factors such as being from an endemic area or having had blood transfusions, especially prior to the commencement of blood-borne virus screening of blood donors.

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.

PubMed

Savitsky, K; Bar-Shira, A; Gilad, S; Rotman, G; Ziv, Y; Vanagaite, L; Tagle, D A; Smith, S; Uziel, T; Sfez, S; Ashkenazi, M; Pecker, I; Frydman, M; Harnik, R; Patanjali, S R; Simmons, A; Clines, G A; Sartiel, A; Gatti, R A; Chessa, L; Sanal, O; Lavin, M F; Jaspers, N G; Taylor, A M; Arlett, C F; Miki, T; Weissman, S M; Lovett, M; Collins, F S; Shiloh, Y

1995-06-23

A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.

Multiple myeloma and related disorders. Lessons from an animal model.

PubMed

Radl, J

1999-02-01

This short review of our own work presents two aspects of the studies on multiple myeloma (MM) in an animal model--the aging C57BL/KaLwRij mouse: 1. the immunological/biological aspect of the development of monoclonal B-cell proliferative disorders, the so-called monoclonal gammopathies (MG), and 2. the use of the mouse myeloma of the 5TMM lines for studies on the etiology/pathogenesis of MM and for developing new ways of treatment of this disease. Our research revealed that there are at least four major mechanisms in the development of MG. Many of the results were confirmed in clinical studies and lead to a new classification of MG according to their biology and possible pathogenesis. Most of MG can be classified into one of the following categories: 1. B-cell malignancies, 2. B-cell benign neoplasia, 3. MG due to an immunodeficiency with T/B cell imbalance, and 4. Antigen driven MG.

Monogenic Autoinflammatory Diseases: Concept And Clinical Manifestations

PubMed Central

De Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela

2013-01-01

The objectives of this review are to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary “periodic fever syndromes”, familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) 6. very rare conditions presenting with autoinflammation and immunodeficiency. PMID:23711932

Assessment, Diagnosis, and Treatment of HIV-Associated Neurocognitive Disorder: A Consensus Report of the Mind Exchange Program

PubMed Central

Antinori, Andrea; Arendt, Gabriele; Grant, Igor; Letendre, Scott; Chair; Muñoz-Moreno, Jose A.; Eggers, Christian; Brew, Bruce; Brouillette, Marie-Josée; Bernal-Cano, Francisco; Carvalhal, Adriana; Christo, Paulo Pereira; Cinque, Paola; Cysique, Lucette; Ellis, Ronald; Everall, Ian; Gasnault, Jacques; Husstedt, Ingo; Korten, Volkan; Machala, Ladislav; Obermann, Mark; Ouakinin, Silvia; Podzamczer, Daniel; Portegies, Peter; Rackstraw, Simon; Rourke, Sean; Sherr, Lorraine; Streinu-Cercel, Adrian; Winston, Alan; Wojna, Valerie; Yazdanpannah, Yazdan; Arbess, Gordon; Baril, Jean-Guy; Begovac, Josip; Bergin, Colm; Bonfanti, Paolo; Bonora, Stefano; Brinkman, Kees; Canestri, Ana; Cholewińska-Szymańska, Graźyna; Chowers, Michal; Cooney, John; Corti, Marcelo; Doherty, Colin; Elbirt, Daniel; Esser, Stefan; Florence, Eric; Force, Gilles; Gill, John; Goffard, Jean-Christophe; Harrer, Thomas; Li, Patrick; de Kerckhove, Linos Van; Knecht, Gaby; Matsushita, Shuzo; Matulionyte, Raimonda; McConkey, Sam; Mouglignier, Antoine; Oka, Shinichi; Penalva, Augusto; Riesenberg, Klaris; Sambatakou, Helen; Tozzi, Valerio; Vassallo, Matteo; Wetterberg, Peter; Drapato, Alicia Wiercińska

2013-01-01

Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)–associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND. PMID:23175555

Rapid Lymphocyte Reconstitution of Unconditioned Immunodeficient Mice with Non-Self-Renewing Multipotent Hematopoietic Progenitors

PubMed Central

Bhattacharya, Deepta; Bryder, David; Rossi, Derrick J.; Weissman, Irving L.

2015-01-01

The replacement of abnormal hematopoietic stem cells (HSCs) with normal transplanted HSCs can correct a wide range of hematologic disorders. Here, we provide evidence that transplantation of more differentiated progenitor cells can be used to more rapidly correct lymphoid deficiencies in unconditioned immunocompromised mice. Transplantation of flk2+ multipotent progenitors led to robust B and T cell reconstitution that was maintained for at least 16 weeks. Antigenic challenge at 16 weeks post-transplantation revealed that reconstituted lymphocytes maintained a functional repertoire. In contrast to the persistent lymphocytic engraftment, myeloid chimerism was lost by 12 weeks post-transplantation consistent with the fact that flk2+ progenitors are non-self-renewing. Thus, while more differentiated progenitors are capable of rescuing lymphoid deficiencies, transplantation of HSCs must be used for the correction of non-lymphoid disorders, and, we propose, very long-term immune reconstitution. Based on recent evidence, we discuss novel strategies to achieve the replacement of abnormal HSCs without the use of cytotoxic conditioning regimens. PMID:16760650

Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification

PubMed Central

Kim, Hyun-Jung; Ko, Young Hyeh; Kim, Ji Eun; Lee, Seung-Sook; Lee, Hyekyung; Park, Gyeongsin; Paik, Jin Ho; Cha, Hee Jeong; Choi, Yoo-Duk; Han, Jae Ho; Huh, Jooryung

2017-01-01

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management. PMID:28592786

Emotional Variability and Clarity in Depression and Social Anxiety

PubMed Central

Thompson, Renee J.; Boden, Matthew Tyler; Gotlib, Ian H.

2016-01-01

Recent research has underscored the importance of elucidating specific patterns of emotion that characterize mental disorders. We examined two emotion traits, emotional variability and emotional clarity, in relation to both categorical (diagnostic interview) and dimensional (self-report) measures of Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) in women diagnosed with MDD only (n=35), SAD only (n=31), MDD and SAD (n=26), or no psychiatric disorder (n=38). Results of the categorical analyses suggest that elevated emotional variability and diminished emotional clarity are transdiagnostic of MDD and SAD. More specifically, emotional variability was elevated for MDD and SAD diagnoses compared to no diagnosis, showing an additive effect for co-occurring MDD and SAD. Similarly diminished levels of emotional clarity characterized all three clinical groups compared to the healthy control group. Dimensional findings suggest that whereas emotional variability is associated more consistently with depression than with social anxiety, emotional clarity is associated more consistently with social anxiety than with depression. Results are interpreted using a threshold- and dose-response framework. PMID:26371579

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

HIV Structural Database

National Institute of Standards and Technology Data Gateway

SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

Induction and Characterization of Immune Responses in Small Animals Using a Venezuelan Equine Encephalitis Virus (VEE) Replicon System, Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Genes

DTIC Science & Technology

2003-01-01

Immunodeficiency Virus Type-1 (HIV-1) Envelope Genes beyond brief excerpts is with permission of the copyright owner, and will save and hold harmless the...VEE) REPLICON SYSTEM, EXPRESSING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) ENVELOPE GENES 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...release, distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Human immunodeficiency virus type 1 (HIV-1) is the lentivirus responsible for the

Clinical status of comorbid bipolar disorder and borderline personality disorder.

PubMed

Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

Molecular mechanisms of mucocutaneous immunity against Candida and Staphylococci

PubMed Central

Maródi, László; Cypowyj, Sophie; Tóth, Beáta; Chernyshova, Liudmyla; Puel, Anne; Casanova, Jean-Laurent

2013-01-01

Signal transducer and activator of transcription (STAT) proteins are key components of the innate and adaptive immune responses to pathogenic microorganisms. Recent research on primary immunodeficiency disorders and the identification of patients carrying germline mutations in STAT1, STAT3, and STAT5B have highlighted the role of human STATs in host defense against various viruses, bacteria, and fungi. Mutations in STAT1 and STAT3 may disrupt various cytokine pathways that control mucocutaneous immunity against Candida species, especially Candida albicans, and Staphylococci, especially Staphylococcus aureus. Here, we consider inborn errors of immunity arising from mutations in either STAT1 or STAT3 that affect mucocutaneous immunity to Candida and Staphylococci. PMID:23040277

Nasal erosion as an uncommon sign of child abuse.

PubMed

Culotta, Paige A; Isaac, Reena; Sarpong, Kwabena; Chandy, Binoy; Cruz, Andrea; Donaruma-Kwoh, Marcella

2018-05-01

While various forms of facial trauma, bruising, burns, and fractures are frequently seen in cases of child abuse, purposeful nasal erosion has rarely been identified as a form of abusive injury. Progressive destruction of nasal tissue in children provokes a wide differential diagnosis crossing multiple subspecialties: infectious, primary immunodeficiencies, inflammatory conditions, malignancy, and genetic disorders. Progressive nasal erosion also can be a manifestation of child abuse. The proposed mechanism is repetitive mechanical denudation of the soft tissue and cartilage resulting in chronic inflammation, bleeding, and ultimately destruction of the insulted tissue. We report 6 cases of child abuse manifesting as overt nasal destruction. Copyright © 2018 Elsevier B.V. All rights reserved.

Depression, Impulse Control Disorder, and Life Style According to Smartphone Addiction.

PubMed

Kim, E Y; Joo, S W; Han, S J; Kim, M J; Choi, S Y

2017-01-01

We examined depression, impulse control disorder, and life style by degree of smartphone addiction. Chi-square tests and ANOVA were used to identify significant variables. CART was used to generate a decision making diagram of variables affecting smartphone addiction. The severe smartphone addiction group had rates of depression and impulse control disorder than the initial smartphone group.

Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

PubMed

Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

2016-02-28

The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

PubMed

Galimberti, Daniela; Prunas, Cecilia; Paoli, Riccardo A; Dell'Osso, Bernardo; Fenoglio, Chiara; Villa, Chiara; Palazzo, Carlotta; Cigliobianco, Michela; Camuri, Giulia; Serpente, Maria; Scarpini, Elio; Altamura, A Carlo

2014-11-01

Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examining Differences between Students with Specific Learning Disabilities and Those with Specific Language Disorders on Cognition, Emotions and Psychopathology

ERIC Educational Resources Information Center

Filippatou, Diamanto; Dimitropoulou, Panagiota; Sideridis, Georgios

2009-01-01

The purpose of the present study was to investigate the differences between students with LD and SLI on emotional psychopathology and cognitive variables. In particular, the study examined whether cognitive, emotional, and psychopathology variables are significant discriminatory variables of speech and language disordered groups versus those…

Family Histories of Anxiety in Overweight Men and Women with Binge Eating Disorder: A Preliminary Investigation

PubMed Central

Blomquist, Kerstin K.; Grilo, Carlos M.

2015-01-01

Objective A preliminary examination of the significance of family histories of anxiety in the expression of binge eating disorder (BED) and associated functioning. Methods Participants were 166 overweight patients with BED assessed using diagnostic interviews. Participants were administered a structured psychiatric history interview about their first-degree relatives (parents, siblings, children) (N=897) to determine lifetime diagnoses of DSM-IV anxiety disorders and completed a battery of questionnaires assessing current and historical eating and weight variables and associated psychological functioning (depression). Results BED patients with a family history of anxiety disorder were significantly more likely than BED patients without a family history of anxiety disorder to have lifetime diagnoses of anxiety disorders and mood disorders but not substance use disorders. A family history of anxiety was not significantly associated with timing or sequencing of age at onset of anxiety disorder, binge eating, dieting, or obesity, or with variability in current levels of binge eating, eating disorder psychopathology, or psychological functioning. Conclusions Although replication with direct interview method is needed, our preliminary findings suggest that a family history of anxiety confers greater risk for comorbid anxiety and mood disorders but is largely unrelated to the development of binge eating, dieting, or obesity and unrelated to variability in eating disorder psychopathology or psychological functioning in overweight patients with BED. PMID:26343481

Mental disorders in HIV/HCV coinfected patients under antiviral treatment for hepatitis C.

PubMed

Martin-Subero, Marta; Diez-Quevedo, Crisanto

2016-12-30

This paper aims to review the epidemiology and management of mental disorders in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, the need for antiviral therapy in this specific population, and current treatment strategies for HIV/HCV patients with psychiatric and/or substance use disorders. This is a narrative review. Data was sourced from electronic databases and was not limited by language or date of publication. HIV infection has become a survivable chronic illness. Prevalence of HCV infection among HIV-infected patients is high ranging from 50% to 90%. Patients with psychiatric diseases have also an increased risk for HIV/HCV coinfection. The most effective strategy to decrease HCV-related morbidity and mortality in coinfection is to achieve viral eradication. Although psychiatric symptoms often appear during antiviral treatment and may be associated with the use of interferon-alpha (IFN-α), recent evidence suggests that many patients with comorbid mental and substance use disorders can be treated safely. Recent data indicate that IFNα-induced psychiatric side effects have a similar prevalence in HIV/HCV coinfected patients than in monoinfected patients and they can be managed and even prevented successfully with psychopharmacological strategies in the frame of a multidisciplinary team. New antivirals offer INF-free therapies for this specific population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Risk factors for eating disorders in Greek- and Anglo-Australian adolescent girls.

PubMed

Mildred, H; Paxton, S J; Wertheim, E H

1995-01-01

Past research indicates ethnicity may be related to eating disorder and related risk factors. The present study examines risk factors for eating disorders in 50 Anglo- and 50 Greek-Australian girls (mean age = 13.5 years). The variables assessed included bulimic tendencies, body dissatisfaction, use of extreme weight loss behaviors (EWLBs), self-esteem, depression and family cohesion and adaptability. Cultural eating patterns were also explored. A stepwise discriminant function analysis to examine whether the two groups could be discriminated on these variables was significant and correctly classified 73.9% of the sample, the chief discriminating variables being Pressure to Eat, EWLBs, and Family Adaptability. Univariate analyses indicated differences between the groups on Pressure to Eat, Family Adaptability, and Mother's Shape. Although the groups were discriminable, a number of variables generally associated with eating disorder did not contribute to the function. These data are discussed in terms of cultural assimilation.

Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help.

PubMed

Compeer, Ewoud B; Janssen, Willemijn; van Royen-Kerkhof, Annet; van Gijn, Marielle; van Montfrans, Joris M; Boes, Marianne

2015-05-10

Common Variable Immunodeficiency (CVID) is the most prevalent primary antibody deficiency, and characterized by defective generation of high-affinity antibodies. Patients have therefore increased risk to recurrent infections of the respiratory and intestinal tract. Development of high-affinity antigen-specific antibodies involves two key actions of B-cell receptors (BCR): transmembrane signaling through BCR-complexes to induce B-cell differentiation and proliferation, and BCR-mediated antigen internalization for class-II MHC-mediated presentation to acquire antigen-specific CD4(+) T-cell help.We identified a variant (L3P) in the B-lymphoid tyrosine kinase (BLK) gene of 2 related CVID-patients, which was absent in healthy relatives. BLK belongs to the Src-kinases family and involved in BCR-signaling. Here, we sought to clarify BLK function in healthy human B-cells and its association to CVID.BLK expression was comparable in patient and healthy B-cells. Functional analysis of L3P-BLK showed reduced BCR crosslinking-induced Syk phosphorylation and proliferation, in both primary B-cells and B-LCLs. B-cells expressing L3P-BLK showed accelerated destruction of BCR-internalized antigen and reduced ability to elicit CD40L-expression on antigen-specific CD4(+) T-cells.In conclusion, we found a novel BLK gene variant in CVID-patients that causes suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4(+) T-cell responses. Both these mechanisms may contribute to hypogammaglobulinemia in CVID-patients.

Predicting human immunodeficiency virus inhibitors using multi-dimensional Bayesian network classifiers.

PubMed

Borchani, Hanen; Bielza, Concha; Toro, Carlos; Larrañaga, Pedro

2013-03-01

Our aim is to use multi-dimensional Bayesian network classifiers in order to predict the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease inhibitors given an input set of respective resistance mutations that an HIV patient carries. Multi-dimensional Bayesian network classifiers (MBCs) are probabilistic graphical models especially designed to solve multi-dimensional classification problems, where each input instance in the data set has to be assigned simultaneously to multiple output class variables that are not necessarily binary. In this paper, we introduce a new method, named MB-MBC, for learning MBCs from data by determining the Markov blanket around each class variable using the HITON algorithm. Our method is applied to both reverse transcriptase and protease data sets obtained from the Stanford HIV-1 database. Regarding the prediction of antiretroviral combination therapies, the experimental study shows promising results in terms of classification accuracy compared with state-of-the-art MBC learning algorithms. For reverse transcriptase inhibitors, we get 71% and 11% in mean and global accuracy, respectively; while for protease inhibitors, we get more than 84% and 31% in mean and global accuracy, respectively. In addition, the analysis of MBC graphical structures lets us gain insight into both known and novel interactions between reverse transcriptase and protease inhibitors and their respective resistance mutations. MB-MBC algorithm is a valuable tool to analyze the HIV-1 reverse transcriptase and protease inhibitors prediction problem and to discover interactions within and between these two classes of inhibitors. Copyright © 2012 Elsevier B.V. All rights reserved.

[Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment].

PubMed

Reus Bañuls, Sergio; Portilla Sogorb, Joaquín; Sanchez-Paya, José; Boix Martínez, Vicente; Giner Oncina, Livia; Frances, Rubén; Such, José; Merino Lucas, Esperanza; Gimeno Gascón, Adelina

2014-01-21

Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. Transversal observational study. HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Accelerated Loss of TCR Repertoire Diversity in Common Variable Immunodeficiency

PubMed Central

Wong, Gabriel K.; Millar, David; Penny, Sarah; Heather, James M.; Mistry, Punam; Buettner, Nico; Bryon, Jane; Huissoon, Aarnoud P.

2016-01-01

Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab deficiencies, growing experimental data now suggest a global disruption of the entire adaptive immune response in a segment of patients. Oligoclonality of the TCR repertoire was previously demonstrated; however, the manner in which it relates to other B cell and T cell findings reported in CVID remains unclear. Using a combination approach of high-throughput TCRβ sequencing and multiparametric flow cytometry, we compared the TCR repertoire diversity between various subgroups of CVID patients according to their B cell immunophenotypes. Our data suggest that the reduction in repertoire diversity is predominantly restricted to those patients with severely reduced class-switched memory B cells and an elevated level of CD21lo B cells (Freiburg 1a), and may be driven by a reduced number of naive T cells unmasking underlying memory clonality. Moreover, our data indicate that this loss in repertoire diversity progresses with advancing age far exceeding the expected physiological rate. Radiological evidence supports the loss in thymic volume, correlating with the decrease in repertoire diversity. Evidence now suggests that primary thymic failure along with other well-described B cell abnormalities play an important role in the pathophysiology in Freiburg group 1a patients. Clinically, our findings emphasize the integration of combined B and T cell testing to identify those patients at the greatest risk for infection. Future work should focus on investigating the link between thymic failure and the severe reduction in class-switched memory B cells, while gathering longitudinal laboratory data to examine the progressive nature of the disease. PMID:27481850

Identifying Challenges to the Integration of Computer-Based Surveillance Information Systems in a Large City Health Department: A Case Study.

PubMed

Jennings, Jacky M; Stover, Jeffrey A; Bair-Merritt, Megan H; Fichtenberg, Caroline; Munoz, Mary Grace; Maziad, Rafiq; Ketemepi, Sherry Johnson; Zenilman, Jonathan

2009-01-01

Integrated infectious disease surveillance information systems have the potential to provide important new surveillance capacities and business efficiencies for local health departments. We conducted a case study at a large city health department of the primary computer-based infectious disease surveillance information systems during a 10-year period to identify the major challenges for information integration across the systems. The assessment included key informant interviews and evaluations of the computer-based surveillance information systems used for acute communicable diseases, human immunodeficiency virus/acquired immunodeficiency syndrome, sexually transmitted diseases, and tuberculosis. Assessments were conducted in 1998 with a follow-up in 2008. Assessments specifically identified and described the primary computer-based surveillance information system, any duplicative information systems, and selected variables collected. Persistent challenges to information integration across the information systems included the existence of duplicative data systems, differences in the variables used to collect similar information, and differences in basic architecture. The assessments identified a number of challenges for information integration across the infectious disease surveillance information systems at this city health department. The results suggest that local disease control programs use computer-based surveillance information systems that were not designed for data integration. To the extent that integration provides important new surveillance capacities and business efficiencies, we recommend that patient-centric information systems be designed that provide all the epidemiologic, clinical, and research needs in one system. In addition, the systems should include a standard system of elements and fields across similar surveillance systems.

Sleep Disturbances in Child and Adolescent Mental Health Disorders: A Review of the Variability of Objective Sleep Markers.

PubMed

Baddam, Suman K R; Canapari, Craig A; van Noordt, Stefon J R; Crowley, Michael J

2018-06-04

Sleep disturbances are often observed in child and adolescent mental health disorders. Although previous research has identified consistent subjective reports of sleep disturbances, specific objective sleep markers have not yet been identified. We evaluated the current research on subjective and objective sleep markers in relation to attention deficit hyperactivity disorders, autism spectrum disorders, anxiety and depressive disorders. Subjective sleep markers are more consistent than objective markers of actigraphy, polysomnography, and circadian measures. We discuss the causes of variability in objective sleep findings and suggest future directions for research.

Seroprevalence of Toxoplasma gondii and concurrent Bartonella spp., feline immunodeficiency virus, feline leukemia virus, and Dirofilaria immitis infections in Egyptian cats

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Immunodeficiency Virus, and Human Leukemia Virus, respectively, and these viruses are immunosuppressive. In the present study, the prevalen...

Microsporum gypseum dermatophytosis in a patient of acquired immunodeficiency syndrome: a rare case report.

PubMed

Bhagra, S; Ganju, S A; Sood, A; Guleria, R C; Kanga, A K

2013-01-01

Microsporum gypseum, a geophillic dermatophyte is rarely isolated from patients with acquired immunodeficiency syndrome. We report tinea corporis due to Microsporum gypseum, an uncommon aetiological agent, in a patient with acquired immunodeficiency syndrome from our region. The clinical presentation resembled psoriasis characterised by atypical, scaly and hyperkeratotic lesions.

78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal Register of May 21, 2013 (78 FR 29755). In that... HIV, symptoms experienced because of HIV or its treatment, and issues related to HIV cure research...

76 FR 72417 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY... Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus... Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) through...

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

PubMed Central

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-01

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

PubMed

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-20

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

Use of the TAT in the assessment of DSM-IV cluster B personality disorders.

PubMed

Ackerman, S J; Clemence, A J; Weatherill, R; Hilsenroth, M J

1999-12-01

The Social Cognition and Object Relations Scale (SCORS), developed by Western, Lohr, Silk, Kerber, and Goodrich (1985), is a diagnostic instrument used to assess an array of psychological functioning by using clinical narratives such as the Thematic Apperception Test (TAT; Murray, 1943) stories. This study investigated the utility of the SCORS to differentiate between Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) antisocial personality disorder (ANPD), borderline personality disorder (BPD), narcissistic personality disorder (NPD), and Cluster C personality disorder (CPD). A sample of 58 patients was separated into four groups: ANPD (n = 9), BPD (n = 21; 18 with a primary BPD diagnosis and 3 with prominent borderline traits who met 4 of the 5 DSM-IV criteria necessary for a BPD diagnosis), NPD (n = 16; 8 with a primary NPD diagnosis and 8 with prominent narcissistic traits who met 4 of the 5 DSM-IV criteria necessary for a NPD diagnosis), and CPD (n = 12). These groups were then compared on the 8 SCORS variables by using 5 TAT cards (1, 2, 3BM, 4, and 13MF). Spearman-Brown correction for 2-way mixed effects model of reliability for the 8 SCORS variables ranged from .70 to .95. The results of categorical and dimensional analyses indicate that (a) SCORS variables can be used to differentiate ANPD, BPD, and NPD; (b) the BPD group scored significantly lower (greater maladjustment) than did the CPD group on certain variables; (c) the BPD group scored significantly lower (greater maladjustment) than did the NPD group on all 8 SCORS variables; (d) the ANPD group scored significantly lower than did the NPD group on certain variables; (e) certain variables were found to be empirically related to the total number of DSM-IV ANPD, BPD, and NPD criteria; and (f) certain variables were found to be empirically related to Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Personality disorder scales. The results of this study are discussed in terms of clinical utility, conceptual, and theoretical implications.

Novel aspects of defensins' involvement in virus-induced autoimmunity in the central nervous system.

PubMed

Kazakos, Evangelos I; Kountouras, Jannis; Polyzos, Stergios A; Deretzi, Georgia

2017-05-01

Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes. Therefore, in this review we describe current contributions in this field and we propose novel hypotheses regarding the potential impact of defensin-related pathways on virus-driven autoimmune neurodegeneration. In this regard, we have previously proposed that abnormal expression of defensins by penetrating the blood-brain barrier (BBB) may contribute to the pathophysiology of Helicobacter pylori-related brain neurodegenerative disorders through variable modulations of innate and adaptive immune responses. We hereby propose that impaired expression of defensins by structural components of the BBB may impede glymphatic circulation and disrupt receptor signalling in pericytes that is essential for microvascular stability, thereby retaining blood-derived toxins and bystander activated T-cells in the brain and further impairing BBB integrity and hampering viral clearance. Autoreactive T-cell infiltrates in neuronaxonal lesions characteristic of chronic central nervous system diseases, such as multiple sclerosis, are directed against both, myelin and non-myelin, antigens the precise nature of which remains enigmatic. Inadequate expression of the autoimmune regulator (AIRE), a gene expressed in medullary thymic epithelial cells, induces the recruitment of defensin-specific T-cells. These cells may access the brain, thereby causing a decrease in defensin expression and subsequent down-regulation of CD91/LRP1-mediated clearance of amyloid-β that ultimately accumulates as protein deposits. It should be highlighted that β-amyloid brain deposits are a hallmark of many neurodegenerative diseases. During human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections, selective elicitation of the VH1-69 antibody subfamily directed against specific, viral glycoprotein epitopes, often correlates with a higher likelihood of developing autoimmune disorders. In addition, we propose that recently described defensin affinity towards the same epitopes may prevent proper viral fusion, but at the expense of augmenting autoimmune reactivity. Moreover, in the context of complex and largely unknown symbiotic relations between host microbiota and pathogenic viruses, we propose that co-stimulation of defensin expression may modulate adaptive immune responses thereby enhancing inflammatory cascades responsible for autoimmunity. Finally, we describe current evidence that supports the hypothesis of a possible involvement of defensins in HCV-related autoimmunity. Exploring further potential implications of human defensins in virus-related autoimmunity may lead to improved strategies for the treatment of neurodegenerative disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality of Human Immunodeficiency Virus Viral Load Testing in Australia

PubMed Central

Best, Susan J.; Gust, Anthony P.; Johnson, Elizabeth I. M.; McGavin, Catherine H.; Dax, Elizabeth M.

2000-01-01

This study determined the proficiencies of laboratories measuring human immunodeficiency virus type 1 (HIV-1) viral loads and the accuracies of two assays used for HIV-1 viral load measurement in Australia and investigated the variability of the new versions of these assays. Quality assessment program panels containing (i) dilutions of HIV-1 subtype B, (ii) replicates of identical samples of HIV-1 subtype B, and (iii) samples of subtype E and B were tested by laboratories. Total variability (within and between laboratories) was tested with quality control samples. The coefficients of variation (CVs) for the Roche AMPLICOR HIV-1 MONITOR version (v) 1.0 and Chiron Quantiplex bDNA 2.0 assays ranged from 53 to 87% and 22 to 31%, respectively. The widespread occurrence of invalid runs with the AMPLICOR HIV-1 MONITOR 1.0 assay was identified. The CVs of the new versions of the assays were 82 to 86% for the AMPLICOR HIV-1 MONITOR v 1.5 assay and 16 to 23% for the Quantiplex bDNA 3.0 assay. For virus dilution samples, all but 5 of 19 laboratories obtained results within 2 standard deviations of the mean. The Quantiplex bDNA 2.0 assay reported values lower than those reported by the AMPLICOR HIV-1 MONITOR version 1.0 assay for samples containing HIV-1 subtype B, whereas the reverse was true for subtype E. Identification and resolution of the problem of invalid runs markedly improved the quality of HIV-1 viral load testing. The variability observed between laboratories and between assays, even the most recent versions, dictates that monitoring of viral load in an individual should always be by the same laboratory and by the same assay. Results for an individual which differ by less than 0.5 log10 HIV-1 RNA copy number/ml should not be considered clinically significant. PMID:11060062

Alexithymia and illness behaviour among female Indian outpatients with multiple somatic symptoms

PubMed Central

Sarkar, Jaydip; Chandra, Prabha

2003-01-01

Sixty Indian muslim women outpatients with multiple somatic complaints of nonorganic origin were assessed for alexithymia and abnormal illness behavior using the Toronto Alexithymia Scale (TAS) and the Illness Behaviour Assessment Schedule (IBAS). Alexithymia represented by TAS scores correlated best with the IBAS variables of communication of affect, somatic illness causal beliefs and denial. Correlation with other IBAS variables was modest to poor.There was no correlation of IBAS variables with age of patient, duration of illness or nature of diagnosis: somatoform disorder or anxiety and depressive disorders, The study showed that alexithymia and illness behaviour are overlapping constructs and confirmed the usefulness of TAS as an instrument to discriminate between patients with anxiety/ depressive disorders and somatoform disorders PMID:21206863

Primary immunodeficiency diseases: a 30-year patient registry from the referral center for primary immunodeficiencies in Greece.

PubMed

Michos, Athanasios; Raptaki, Maria; Tantou, Sofia; Tzanoudaki, Marianna; Spanou, Kleopatra; Liatsis, Manolis; Constantinidou, Nikki; Paschali, Evangelia; Varela, Ioanna; Moraloglou, Olga; Bakoula, Chryssa; Kanariou, Maria

2014-10-01

Primary Immunodeficiencies (PID) represent a group of heterogeneous immune diseases with important biological significance. We reviewed the records of children diagnosed with PID in the Referral Center for PID in our country in order to describe the epidemiological, clinical and laboratory characteristics of immunodeficient patients. During a 30-year period, 147 patients (101 males, 68.7 %), with a mean age of 6.5 years at the time of diagnosis, were diagnosed with PID. The most prevalent diagnoses of PID were: "Combined Immunodeficiency" in 46 (31.3 %) patients, "Well-defined immunodeficiency syndrome" in 35 (23.1 %) patients, "Predominantly antibody deficiency" in 30 (20.4 %) patients and "Congenital defect of phagocyte function or both" in 28 (19 %) patients. There was a higher prevalence of males with "Combined immunodeficiency" (p < 0.033) and "Predominantly antibody deficiency" (p < 0.02) compared to females. The median age of children at the onset of symptoms and at the time of diagnosis was 0.5y (IQR: 0.1-2.5) and 2y (IQR: 0.6-7.2), respectively. The median diagnostic delay was 0.9y (IQR: 0.2-4.8). This period was shorter for patients with "Combined immunodeficiency" [median 0.3y (IQR: 0.1-1)], and longer for those with "Predominantly antibody deficiency" [median 3.2y (IQR: 0.2-5.9) or "Disease of immune dysregulation" [median 3.2y (IQR: 0.1-6.6)]. Comparing the rates in our population with those of the European Registry (ESID), the rates of "Combined immunodeficiencies", "Well-defined syndromes" and "Congenital birth defects and/or function of phagocytes" were significantly higher in this study (p <0,001). PID registry analysis improves knowledge in the field of Immunology and enhances awareness, early detection, diagnosis, and management of this rare but significant group of diseases.

Estimating the impact of vaccination in acute SHIV-SIV infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro, Ruy

2008-01-01

Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required,more » in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.« less

Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with visual function.

PubMed

Kalyani, Partho S; Fawzi, Amani A; Gangaputra, Sapna; van Natta, Mark L; Hubbard, Larry D; Danis, Ronald P; Thorne, Jennifer E; Holland, Gary N

2012-03-01

To evaluate relationships between retinal vessel caliber and tests of visual function among people with AIDS. Longitudinal, observational cohort study. We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Visual function was evaluated with best-corrected visual acuity, Goldmann perimetry, automated perimetry (Humphrey Field Analyzer), and contrast sensitivity (CS) testing. Semi-automated grading of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, sought independent relationships between indices and visual function variables. Included were 1250 participants. Smaller AVR was associated with reduced visual field by Goldmann perimetry (P = .003) and worse mean deviation (P = .02) on automated perimetry and possibly with worse pattern standard deviation (PSD) on automated perimetry (P = .06). There was a weak association between smaller AVR and worse CS (P = .07). Relationships were independent of antiretroviral therapy and level of immunodeficiency (CD4+ T lymphocyte count, human immunodeficiency virus [HIV] RNA blood level). On longitudinal analysis, retinal vascular indices at baseline did not predict changes in visual function. Variation in retinal vascular indices is associated with abnormal visual function in people with AIDS, manifested by visual field loss and possibly by reduced CS. Relationships are consistent with the hypothesis that HIV-related retinal vasculopathy is a contributing factor to vision dysfunction among HIV-infected individuals. Longitudinal studies are needed to determine whether changes in indices predict change in visual function. Copyright © 2012 Elsevier Inc. All rights reserved.

Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group.

PubMed

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

2017-11-01

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 across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1-12 months for adult patients and every 3-6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients. © 2017 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group

PubMed Central

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.

2017-01-01

Summary 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 across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1–12 months for adult patients and every 3–6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients. PMID:28708268

The effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth in squamous cell carcinoma of the head and neck.

PubMed

Teknos, Theodoros N; Islam, Mozaffarul; Arenberg, Douglas A; Pan, Quintin; Carskadon, Shannon L; Abarbanell, Aaron M; Marcus, Benjamin; Paul, Supriti; Vandenberg, Curtis D; Carron, Michael; Nor, Jacques E; Merajver, Sofia D

2005-03-01

To assess the effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth rate in human squamous cell carcinoma (SCC). Three human SCC cell lines were used in this study for both in vitro and in vivo investigations. Conditioned media from untreated and tetrathiomolybdate-treated cell lines were compared with regard to cytokine levels, endothelial cell chemotaxis, endothelial cell tubule formation, and migration and the ability to induce angiogenesis in a rat aortic ring array. In vivo UM-SCC-38 was seeded onto tissue-engineered scaffolds and surgically implanted into the flanks of immunodeficient mice. Tumor growth rates and the level of angiogenesis were compared after 2 weeks of therapy. A tertiary care facility. In this study, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by head and neck SCC (HNSCC) cell lines in vitro. Furthermore, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by HNSCC cell lines in vitro. Furthermore, tetrathiomolybdate treatment of HNSCC cell lines results in significantly decreased endothelial cell chemotaxis, tubule formation, and neovascularization in a rat aortic ring assay. This in vitro evidence of decreased angiogenesis by tetrathiomolybdate is confirmed in vivo by using a severe combined immunodeficiency disorder mouse model in which tetrathiomolybdate therapy is shown to prevent human blood vessel formation. Finally, human HNSCC implanted into immunodeficient mice grow to a much larger size in untreated mice compared with those treated with 0.7 mL/kg per day of oral tetrathiomolybdate. These findings illustrate the ability of tetrathiomolybdate to down-regulate proinflammatory and proangiogenic cytokines in HNSCC. These observations are potentially exciting from a clinical perspective because a global decrease in these cytokines may decrease tumor aggressiveness and reverse the resistance to chemotherapy and radiation therapy seen in this tumor type.

Fatal Human Case of Zika and Chikungunya Virus Co-Infection with Prolonged Viremia and Viruria.

PubMed

Silva, Kelly R; Bica, Blanca E R G; Pimenta, Eduardo S; Serafim, Rodrigo B; Abreu, Mirhelen M; Gonçalves, Jorge L S; Santana, Larissa de S; Cabral-Castro, Mauro J; Peralta, José M; Cavalcanti, Marta G

2018-06-21

Zika virus (ZIKV) infection usually presents as a mild and self-limited illness, but it may be associated with severe outcomes. We describe a case of a 30-year-old man with systemic erythematous lupus and common variable immunodeficiency who became infected with both Zika (ZIKV) and Chikungunya (CHIKV) virus during the 2016 outbreak in Rio de Janeiro, Brazil. The patient presented with intense wrist and right ankle arthritis, and ZIKV RNA and virus particles were detected in synovial tissue, blood and urine, and CHIKV RNA in serum sample, at the time of the diagnosis. During the follow up, ZIKV RNA persisted for 275 days post symptoms onset. The patient evolved with severe arthralgia/arthritis and progressive deterioration of renal function. Fatal outcome occurred after 310 days post ZIKV and CHIKV co-infection onset. The results show the development of severe disease and fatal outcome of ZIKV infection in an immunosuppressed adult. The data suggests a correlation between immunodeficiency and prolonged ZIKV RNA shedding in both blood and urine with progressive disease. The results also indicate a possible role for arbovirus co-infections as risk factors for severe and fatal outcomes from ZIKV infection.

Is AIDS education related to condom acquisition?

PubMed

Rickert, V I; Gottlieb, A A; Jay, M S

1992-04-01

The acquisition and subsequent use of condoms are two important behaviors that sexually active adolescents must adopt to reduce the transmission of human immunodeficiency virus (HIV). The aims of this study were: first, to evaluate whether combining prescriptions for free condoms with anticipatory guidance would increase the number of adolescents actually using the prescription-redemption plan; and second, to see if education about acquired immunodeficiency syndrome (AIDS) might make adolescents more willing to obtain an HIV blood test. Adolescents were randomly assigned to one of three groups, but only those who were sexually active were included in the data analyses. Each participant was given a prescription to be redeemed for free condoms at the hospital pharmacy, and each was privately offered a confidential, free HIV blood test. Education about AIDS did not increase the likelihood that adolescents would take the blood test, since only seven subjects did so. Our logistic regression model showed the most significant variables influencing a teenager to obtain condoms were gender, socioeconomic status, lifetime number of partners, and experimental condition. Anticipatory guidance concerning HIV promoted the use of the prescription-redemption plan especially among more sexually active males who come from middle-class families.

A Cognitive Dimensional Approach to Understanding Shared and Unique Contributions to Reading, Math, and Attention Skills.

PubMed

Child, Amanda E; Cirino, Paul T; Fletcher, Jack M; Willcutt, Erik G; Fuchs, Lynn S

2018-05-01

Disorders of reading, math, and attention frequently co-occur in children. However, it is not yet clear which cognitive factors contribute to comorbidities among multiple disorders and which uniquely relate to one, especially because they have rarely been studied as a triad. Thus, the present study considers how reading, math, and attention relate to phonological awareness, numerosity, working memory, and processing speed, all implicated as either unique or shared correlates of these disorders. In response to findings that the attributes of all three disorders exist on a continuum rather than representing qualitatively different groups, this study employed a dimensional approach. Furthermore, we used both timed and untimed academic variables in addition to attention and activity level variables. The results supported the role of working memory and phonological awareness in the overlap among reading, math, and attention, with a limited role of processing speed. Numerosity was related to the comorbidity between math and attention. The results from timed variables and activity level were similar to those from untimed and attention variables, although activity level was less strongly related to cognitive and academic/attention variables. These findings have implications for understanding cognitive deficits that contribute to comorbid reading disability, math disability, and/or attention-deficit/hyperactivity disorder.

38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... to an individual whom the patient has, during the process of professional counseling or of testing to...

38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... to an individual whom the patient has, during the process of professional counseling or of testing to...

38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... to an individual whom the patient has, during the process of professional counseling or of testing to...

38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... to an individual whom the patient has, during the process of professional counseling or of testing to...

38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... to an individual whom the patient has, during the process of professional counseling or of testing to...

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in...

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in...

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in...

Tinea imbricata as a clue to occult immunodeficiency.

PubMed

Maroñas Jiménez, Lidia; Monsálvez, Verónica; Gutiérrez García-Rodrigo, Carlota; Postigo Llorente, Concepción

2014-01-01

Tinea imbricata (TI) is a geographically restricted dermatophytosis with distinctive clinical and immunologic features. We present a case of TI occurring in a native Brazilian child with previously undiagnosed human immunodeficiency virus infection. Physicians should bear in mind that diagnosis of TI may be a clinical clue to potentially serious underlying immunodeficiency. © 2014 Wiley Periodicals, Inc.

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent...

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent...

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent...

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent...

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid reagent...

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

Code of Federal Regulations, 2010 CFR

2010-07-01

... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in... may be disclosed to a Federal, State, or local public health authority, charged under Federal or State...

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

Code of Federal Regulations, 2011 CFR

2011-07-01

... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in... may be disclosed to a Federal, State, or local public health authority, charged under Federal or State...

Responsibility for managing musculoskeletal disorders--a cross-sectional postal survey of attitudes.

PubMed

Larsson, Maria E H; Nordholm, Lena A

2008-08-05

Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683-693 individuals could be included. Attitudes were measured by the "Attitudes regarding Responsibility for Musculoskeletal disorders" (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found. The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92-9.20), musculoskeletal disorder related sick leave (OR 2.31-3.07) and no education beyond the compulsory level (OR 3.12-4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else. Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people's attitudes should be taken into account.

Responsibility for managing musculoskeletal disorders – A cross-sectional postal survey of attitudes

PubMed Central

Larsson, Maria EH; Nordholm, Lena A

2008-01-01

Background Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. Methods A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683–693 individuals could be included. Attitudes were measured by the "Attitudes regarding Responsibility for Musculoskeletal disorders" (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. Results A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found. The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92–9.20), musculoskeletal disorder related sick leave (OR 2.31–3.07) and no education beyond the compulsory level (OR 3.12–4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else. Conclusion Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people's attitudes should be taken into account. PMID:18681967

Immunoglobulin deficiency in patients with Streptococcus pneumoniae or Haemophilus influenzae invasive infections.

PubMed

Martinot, Martin; Oswald, Laetitia; Parisi, Elisabeth; Etienne, Elodie; Argy, Nicolas; Grawey, Isabelle; De Briel, Dominique; Zadeh, Mahsa Mohseni; Federici, Laure; Blaison, Gilles; Koebel, Christelle; Jaulhac, Benoit; Hansmann, Yves; Christmann, Daniel

2014-02-01

Immunoglobulin (Ig) deficiency is a well-known risk factor for Streptococcus pneumoniae or Haemophilus influenzae infections and noteworthy invasive diseases. However, the proportion of these deficiencies in cases of invasive disease is unknown. The objective of this study was to evaluate the rate of Ig deficiency in cases of invasive disease. A prospective study was conducted from January 2008 to October 2010 in two French hospitals. Measurement of Ig levels was carried out in patients hospitalized for invasive diseases. A total of 119 patients were enrolled in the study, with nine cases of H. influenzae and 110 cases of S. pneumoniae invasive disease. There were 18 cases of meningitis, 79 of invasive pneumonia, and 22 other invasive diseases. Forty-five patients (37.8%) had an Ig abnormality, 37 of whom had an Ig deficiency (20 IgG <6g/l, four isolated IgA <0.7g/l, and 13 isolated IgM <0.5g/l), while eight had an elevated monoclonal paraprotein. Nineteen of these 45 patients had a clearly defined Ig abnormality, with five primary deficiencies (three common variable immunodeficiencies and two complete IgA deficiencies) and 14 secondary deficiencies, mainly lymphoproliferative disorders. All these deficiencies were either not known or not substituted. Humoral deficiency is frequent in patients with S. pneumoniae or H. influenzae invasive disease and Ig dosage should be proposed systematically after such infections. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Homeless and Nonhomeless United States Veterans.

PubMed

Noska, Amanda J; Belperio, Pamela S; Loomis, Timothy P; O'Toole, Thomas P; Backus, Lisa I

2017-07-15

Veterans are disproportionately affected by human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Homeless veterans are at particularly high risk for HIV, HCV, and HBV due to a variety of overlapping risk factors, including high rates of mental health disorders and substance use disorders. The prevalence of HIV, HCV, and HBV among homeless veterans nationally is currently unknown. This study describes national testing rates and prevalence of HIV, HCV, and HBV among homeless veterans. Using data from the Department of Veterans Affairs (VA) Corporate Warehouse Data from 2015, we evaluated HIV, HCV, and HBV laboratory testing and infection confirmation rates and diagnoses on the Problem List for nonhomeless veterans and for veterans utilizing homeless services in 2015. Among 242740 homeless veterans in VA care in 2015, HIV, HCV, and HBV testing occurred in 63.8% (n = 154812), 78.1% (n = 189508), and 52.8% (n = 128262), respectively. The HIV population prevalence was 1.52% (3684/242740) among homeless veterans, compared with 0.44% (23797/5424685) among nonhomeless veterans. The HCV population prevalence among homeless veterans was 12.1% (29311/242740), compared with 2.7% (148079/5424685) among nonhomeless veterans, while the HBV population prevalence was 0.99% (2395/242740) for homeless veterans and 0.40% (21611/5424685) among nonhomeless veterans. To our knowledge this work represents the most comprehensive tested prevalence and population prevalence estimates of HIV, HCV, and HBV among homeless veterans nationally. The data demonstrate high prevalence of HIV, HCV, and HBV among homeless veterans, and reinforce the need for integrated healthcare services along with homeless programming. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chronic alcohol increases CD8+ T-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques.

PubMed

Katz, Paige S; Siggins, Robert W; Porretta, Connie; Armstrong, Megan L; Zea, Arnold H; Mercante, Donald E; Parsons, Christopher; Veazey, Ronald S; Bagby, Gregory J; Nelson, Steve; Molina, Patricia E; Welsh, David A

2015-12-01

Activated CD8+ T-cells correlate with viral load and may foretell antiretroviral therapy (ART) failure. HIV infection has been suggested to accelerate immunosenescence through chronic persistent inflammation. Alcohol-use disorders (AUD) are prevalent in persons living with HIV/AIDS (PLWHA). We tested the hypothesis that hazardous alcohol consumption accelerates immune activation and immunosenescence. Immune activation and immunosenescence were examined in CD8+ T lymphocytes (CD3+CD4-CD8+) isolated from intestinal biopsies, axillary lymph nodes, and peripheral blood mononuclear cells (PBMCs) of chronic binge alcohol (CBA)-consuming simian immunodeficiency virus (SIV)-infected male rhesus macaques with and without antiretroviral therapy (ART; CBA/ART+, CBA/ART-) and in PBMCs isolated from a cohort of PLWHA. Polychromatic flow cytometry was used to phenotype cells isolated from intestinal biopsies, lymph nodes, and peripheral blood from rhesus macaques and PLWHA. The Alcohol Use Disorders Identification Test (AUDIT) identified hazardous alcohol drinking in PLWHA. Viral load was determined by RT-qPCR and telomere length was measured using qPCR. PBMC CD8+ T-cell activation (CD38+HLA-DR+) and immunosenescence (CD28-) were increased over baseline levels (857% ± 334, p < 0.05; 398% ± 80, p < 0.05, respectively) only in CBA animals not receiving ART. Viral load correlated with CD8+ T-cell immunosenescence in macaque PBMCs (r(s) = 0.49, p = 0.02). Activated immunosenescent T-cell (CD8+CD38+CD28-) frequencies in PBMCs from PLWHA significantly correlated with AUDIT scores (r(s) = 0.75, p = 0.001), while no correlation was observed with CD4+ T-cell and AUDIT scores (r(s) = -0.24, p = 0.38). Activated immunosenescent T-cells had shorter telomeres than CD8+ T-cells (CD8+CD28+) from PLWHA. Our results suggest that CBA and AUD augment immune activation and immunosenescence in SIV-infected macaques and PLWHA. Copyright © 2015 Elsevier Inc. All rights reserved.

The interaction between awareness of one's own speech disorder with linguistics variables: distinctive features and severity of phonological disorder.

PubMed

Dias, Roberta Freitas; Melo, Roberta Michelon; Mezzomo, Carolina Lisbôa; Mota, Helena Bolli

2013-01-01

To analyze the possible relationship among the awareness of one's own speech disorder and some aspects of the phonological system, as the number and the type of changed distinctive features, as well as the interaction among the severity of the disorder and the non-specification of distinctive features. The analyzed group has 23 children with diagnosis of speech disorder, aged 5:0 to 7:7. The speech data were analyzed through the Distinctive Features Analysis and classified by the Percentage of Correct Consonants. One also applied the Awareness of one's own speech disorder test. The children were separated in two groups: with awareness of their own speech disorder established (more than 50% of correct identification) and without awareness of their own speech disorder established (less than 50% of correct identification). Finally, the variables of this research were submitted to analysis using descriptive and inferential statistics. The type of changed distinctive features weren't different between the groups, as well as the total of changed features and the severity disorder. However, a correlation between the severity disorder and the non-specification of distinctive features was verified, because the more severe disorders have more changes in these linguistic variables. The awareness of one's own speech disorder doesn't seem to be directly influenced by the type and by the number of changed distinctive features, neither by the speech disorder severity. Moreover, one verifies that the greater phonological disorder severity, the greater the number of changed distinctive features.

Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

PubMed Central

Karalunas, Sarah L.; Geurts, Hilde M.; Konrad, Kerstin; Bender, Stephan; Nigg, Joel T.

2014-01-01

Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and Methodology Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. Findings Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders. PMID:24628425

Surface receptors on neutrophils and monocytes from immunodeficient and normal horses.

PubMed Central

Banks, K L; McGuire, T C

1975-01-01

Surface receptors on peripheral blood neutrophils and monocytes from normal and immunodeficient horses have been studied. Sheep erythrocytes (SRBC) coated with IgG, IgM, and complement but not IgG(T), readily bound to normal equine monocytes and neutrophils. More than 4000 molecules of IgG were required to sensitize each SRBC for adherence to monocytes, and more than 12,000 molecules were required for adherence to neutrophils. Young horses with a severe combined immunodeficiency had an almost total absence of lymphocytes, but normal numbers of monocytes and neutrophils. The number of receptors for immunoglobulin, complement, and phytolectin on monocytes and neutrophils from immunodeficient animals were similar to those on the cells of normal horses. Although the precursor cells of lymphocytes of horses with combined immunodeficiency appear to be defective, no defect in the other cellular products of the bone marrow were apparent. PMID:1126740

Glutathione and growth inhibition of Mycobacterium tuberculosis in healthy and HIV infected subjects

PubMed Central

Venketaraman, Vishwanath; Rodgers, Tatanisha; Linares, Rafael; Reilly, Nancy; Swaminathan, Shobha; Hom, David; Millman, Ariel C; Wallis, Robert; Connell, Nancy D

2006-01-01

Intracellular levels of glutathione are depleted in patients with acquired immunodeficiency syndrome in whom the risk of tuberculosis, particularly disseminated disease is many times that of healthy individuals. In this study, we examined the role of glutathione in immunity against tuberculosis infection in samples derived from healthy and human immunodeficiency virus infected subjects. Our studies confirm that glutathione levels are reduced in peripheral blood mononuclear cells and in red blood cells isolated from human immunodeficiency virus-infected subjects (CD4>400/cumm). Furthermore, treatment of blood cultures from human immunodeficiency virus infected subjects with N-acetyl cysteine, a glutathione precursor, caused improved control of intracellular M. tuberculosis infection. N-acetyl cysteine treatment decreased the levels of IL-1, TNF-α, and IL-6, and increased the levels of IFN-γ in blood cultures derived from human immunodeficiency virus-infected subjects, promoting the host immune responses to contain M. tuberculosis infection successfully. PMID:16504020

Relationship of Social Network to Protective Factors in Suicide and Alcohol Use Disorder Intervention for Rural Yup’ik Alaska Native Youth

PubMed Central

Philip, Jacques; Ford, Tara; Henry, David; Rasmus, Stacy; Allen, James

2015-01-01

Suicide and alcohol use disorders are significant Alaska Native health disparities, yet there is limited understanding of protection and no studies of social network factors in protection in this or other populations. The Qungasvik intervention enhances protective factors from suicide and alcohol use disorders through activities grounded in Yup’ik cultural practices and values. Identification of social network factors associated with protection within the cultural context of these tight, close knit, and high density rural Yup’ik Alaska Native communities in southwest Alaska can help identify effective prevention strategies for suicide and alcohol use disorder risk. Using data from ego-centered social network and protective factors from suicide and alcohol use disorders surveys with 50 Yup’ik adolescents, we provide descriptive data on structural and network composition variables, identify key network variables that explain major proportions of the variance in a four principal component structure of these network variables, and demonstrate the utility of these key network variables as predictors of family and community protective factors from suicide and alcohol use disorder risk. Connections to adults and connections to elders, but not peer connections, emerged as predictors of family and community level protection, suggesting these network factors as important intervention targets for intervention. PMID:27110094

Variety Is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-Life Events

ERIC Educational Resources Information Center

Loth, Eva; Happe, Francesca; Gomez, Juan Carlos

2010-01-01

This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in…

Feline vaccine-associated fibrosarcoma induced by aluminium compound in two cats: short communication.

PubMed

Deim, Zoltán; Palmai, Nimród; Cserni, Gábor

2008-03-01

Two cases of feline vaccine-associated fibrosarcoma (FVAF) are reported. The excised tumours were both characterised as well circumscribed, subcutaneous, firm and white with central necrosis. Histopathologically, they consisted of well-differentiated and variably sized and shaped anaplastic cells, characterised by marked nuclear and cellular pleomorphism including giant cells. The mitotic activity was low. Aluminium was demonstrated in the central necrosis and giant cells. Neoplastic cells were positive for vimentin and negative for desmin and cytokeratin. The presence of feline sarcoma virus and feline immunodeficiency virus could not be detected by PCR in either case.

Hypogammaglobulinemia associated with nodular lymphoid hyperplasia of the intestine and pernicious anaemia.

PubMed

Ouakaa-Kchaou, Asma; Trad, Dorra; Boussourra, Houda; Bibani, Norsaf; Elloumi, Héla; Kochlef, Asma; Gargouri, Dalila; Kharrat, Jamel

2015-11-01

Nodular lymphoid hyperplasia of the gastrointestinal tract, recurrent acute pulmonary infections and autoimmune disease are well-recognized complications of common variable immunodeficiency. We aimed to focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid and hyperplasia of the gastrointestinal tract coexisting with hypogammaglobulinemia. We report the case of nodular lymphoid hyperplasia associated with pernicious anaemia in a young man with hypogammaglobulinemia and a long history of pulmonary infections. The considerable point was a mismatch primary clinical diagnosis of familial adenomatous polyposis, due to prominent polyplike endoscopic appearance of the lesions throughout the digestive tract.

Intra cranial granulomatous disease in common variable immunodeficiency: Case series and review of the literature.

PubMed

Najem, Catherine E; Springer, Jason; Prayson, Richard; Culver, Daniel A; Fernandez, James; Tavee, Jinny; Hajj-Ali, Rula A

2018-06-01

Common variable immunodeficiency (CVID) is typically characterized by hypogammaglobulinemia and often but not always recurrent infections. Paradoxically, 8-22% of patients with CVID develop granulomatous disease. Granulomata have been described in many organs including the lungs, skin, liver, spleen, kidneys, eyes, lymph nodes, and intestines. Data about central nervous system (CNS) involvement in CVID are extremely rare. We aim to describe a case series and include an extensive literature review of CNS involvement in CVID to understand the different features and patterns of the disease. We searched the English Pubmed database for relevant articles between 1950 and 2014 using the Key Words "common variable immunodeficiency", "granulomatous disease", "brain", "sarcoidosis", and "sarcoid-like syndrome". Data from all case series, surveys, systematic reviews, and individual case reports, as well as retrospective studies were extracted. A total of 15 patients were reported in the literature. We combined our experience with four additional patients from The Cleveland Clinic between 2009 and 2014. Demographics, clinical features, laboratory and imaging findings, treatment and follow-up were extracted for the 19 patients and summarized descriptively. Female sex and Caucasian race represented 63.2% (12/19), and 80% of the patients, respectively. The mean age of CVID diagnosis was 24 years; mean age when the CNS disease was diagnosed was 21.5 years. 68.4% of the patients (13/19) had granulomas involving ≥2 organs including the central nervous system, 31.6% (6/19) had CNS granulomas only. Associated granulomatous diseases occurred in lungs (72.7%), lymph nodes (27.2%), spleen (27.2%), eyes (18.1%), liver (18.1%), parotid glands (9%), and skin (9%). Fifty-three percent (10/19) of the patients had documented recurrent infections, all of them being upper respiratory tract infections. CNS manifestations included seizures (31.6%), headaches (21%), vision loss (15.7%), decreased cognition (10.5%), focal weakness (5.2%), nystagmus (5.2%), ataxia (5.2%), coma (5.2%), polyuria, and polydipsia (5.2%). Brain mass was the most common radiologic finding (70%) followed by leptomeningeal enhancement (10%), non-specific white matter lesions (10%) and absence of normal signal of the neurohypophysis (10%). Brain pathology was available in 12 patients: findings included granulomatous disease in 83.3%, angiocentric granulomas in 50%, vasculitis without granulomas in 8.3%, and lymphocytic infiltrate of the meninges with diffuse non-caseating granulomas in 8.3%. Cerebrospinal fluid analysis revealed elevated total proteins with/or without lymphocytic pleocytosis in 80%. CNS disease is a rare challenging complication of CVID. Patients with brain involvement are generally female, Caucasian, and likely have lung involvement. Although immunoglobulin and steroids remain the first line of treatment, other immunosuppressive agents have shown some promise with regards to recurrent relapsing presentations. Copyright © 2017. Published by Elsevier Inc.

Exploring Rural Disparities in Medical Diagnoses Among Veterans With Transgender-related Diagnoses Utilizing Veterans Health Administration Care.

PubMed

Bukowski, Leigh A; Blosnich, John; Shipherd, Jillian C; Kauth, Michael R; Brown, George R; Gordon, Adam J

2017-09-01

Research shows transgender individuals experience pronounced health disparities compared with their nontransgender peers. Yet, there remains insufficient research about health differences within transgender populations. This study seeks to fill this gap by exploring how current urban/rural status is associated with lifetime diagnosis of mood disorder, alcohol dependence disorder, illicit drug abuse disorder, tobacco use, posttraumatic stress disorder, human immunodeficiency virus, and suicidal ideation or attempt among veterans with transgender-related diagnoses. This study used a retrospective review of The Department of Veterans Affairs (VA) administrative data for transgender patients who received VA care from 1997 through 2014. Transgender patients were defined as individuals that had a lifetime diagnosis of any of 4 International Classification of Diseases-9 diagnosis codes associated with transgender status. Independent multivariable logistic regression models were used to explore associations of rural status with medical conditions. Veterans with transgender-related diagnoses residing in small/isolated rural towns had increased odds of tobacco use disorder (adjusted odds ratio=1.39; 95% confidence intervals, 1.09-1.78) and posttraumatic stress disorder (adjusted odds ratio=1.33; 95% confidence intervals, 1.03-1.71) compared with their urban transgender peers. Urban/rural status was not significantly associated with other medical conditions of interest. This study contributes the first empirical investigations of how place of residence is associated with medical diagnoses among veterans with transgender-related diagnoses. The importance of place as a determinant of health is increasingly clear, but for veterans with transgender-related diagnoses this line of research is currently limited. The addition of self-reported sex identity data within VA electronic health records is one way to advance this line of research.

Mechanisms of Cytotoxicity of the AIDS Virus.

DTIC Science & Technology

1991-10-10

lentiviruses causes immunosuppression in cats ( feline immunodeficiency virus) (Pederson et al., 1987; Luciw et al., 1989), sheep (visna virus) (Haas et...determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. 4. Simian... Immunodeficiency Virus Negative Factor Suppresses the Level of Viral mRNA in COS cells 5. Protein N-myristoylation/AIDS/fatty acid analogs 6. Functional

75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor Deferral... Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus... Acid Test (NAT) and Hepatitis C Virus (HCV) NAT, on testing individual samples or pooled samples from...

Toxoplasmic Encephalitis in Patient with Acquired Immunodeficiency Syndrome.

PubMed

Lee, Sang-Bok; Lee, Tae-Gyu

2017-04-01

Toxoplasmic encephalitis (TE) is an opportunistic infection found in immunocompromised patients and TE related cerebral mass lesion is often reported in acquired immunodeficiency acquired immunodeficiency syndrome (AIDS) patients. However, incidence of TE related AIDS in Korea is still rare and is unfamiliar to neurosurgeons. Differential diagnosis is needed to rule out other brain lesions. A 39-year-old man visited the emergency room with rapid progressive left hemiparesis. Magnetic resonance imaging showed a ring-enhanced mass lesion in his right frontal lobe. Human immunodeficiency virus and Toxoplasma gondii immunoglobulin G were tested positive by a serologic test. We report here a rare case of patient with TE related AIDS.

Distribution and clinical aspects of primary immunodeficiencies in a Taiwan pediatric tertiary hospital during a 20-year period.

PubMed

Lee, Wen-I; Kuo, Ming-Ling; Huang, Jing-Long; Lin, Syh-Jae; Wu, Cheng-Jang

2005-03-01

Recent advances in immunologic techniques have lead to increased recognition of primary immunodeficiencies. A review of patients with suspected immunodeficiencies in a Taiwan tertiary hospital from January 1985 to October 2004 and molecular/genetic analyses done on some patients were investigated. Of the 403 patients selected based on the International Classification of Disease, Ninth Revision, 37 patients with PID (8 females and 29 males) were identified: 17 (46%) with antibody production deficiencies, nine (24%) with defective phagocyte function, four (11%) with combined B and T cell immunodeficiencies, seven (19%) with T cell deficiencies, but none with primary complement deficiencies. Those with secondary immunodeficiencies were excluded from the study. Recurrent sinopulmonary infections (62%) were the most common clinical manifestation, followed by sepsis (57%), severe skin infection (40%), splenomegaly/hepatomegaly (27%), central nervous system dysfunction (22%), chronic diarrhea (22%), and failure to thrive (19%). Seven (19%) patients died, five of infections, one of disseminated intravascular coagulopathy and one of hepatocellular carcinoma. Six novel mutations were found from 11 agreed patients. This is the first report on primary immunodeficiencies in Taiwan covering a 20-year period.

Comparing immunocompetent and immunodeficient mice as animal models for bone tissue engineering.

PubMed

Zhang, Y; Li, X; Chihara, T; Mizoguchi, T; Hori, A; Udagawa, N; Nakamura, H; Hasegawa, H; Taguchi, A; Shinohara, A; Kagami, H

2015-07-01

To understand the differences and similarities between immunocompetent and immunodeficient mice as ectopic transplantation animal models for bone tissue engineering. Osteogenic cells from mouse leg bones were cultured, seeded on β-TCP granules, and transplanted onto the backs of either immunocompetent or immunodeficient nude mice. At 1, 2, 4, and 8 weeks postoperatively, samples were harvested and evaluated by hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemical staining and quantitative PCR. In immunocompetent mice, inflammatory cell infiltration was evident at 1 week postoperatively and relatively higher expression of TNF-α and IL-4 was observed. In immunodeficient mice, new bone area and the number of TRAP-positive cells were larger at 4 weeks than in immunocompetent mice. The volume of new bone area in immunodeficient mice was reduced by 8 weeks. Bone regeneration was feasible in immunocompetent mice. However, some differences were observed between immunocompetent and immunodeficient mice in the bone regeneration process possibly due to different cytokine expression, which should be considered when utilizing in vivo animal models. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human immunodeficiency virus-associated precursor T-lymphoblastic leukemia/lymphoblastic lymphoma: report of a case and review of the literature.

PubMed

Lorenzon, Debora; Perin, Tiziana; Bulian, Pietro; De Re, Valli; Caggiari, Laura; Michieli, Mariagrazia; Manuele, Rosa; Spina, Michele; Gattei, Valter; Fasan, Marco; Tirelli, Umberto; Canzonieri, Vincenzo

2009-07-01

We describe a case of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma in a 43-year-old Italian man with a history of human immunodeficiency virus infection lasting 9 years. Immunoperoxidase stains showed that neoplastic cells were positive for CD3, TdT, CD45, CD10, CD1a, CD2, CD7, CD5, and CD43 (focal). The proliferation rate was approximately 70%, assessed by Ki-67/MIB-1 staining. Flow cytometry of the marrow aspirate revealed an intermediate/cortical T-lymphoblastic phenotype: negative for surface CD3 and positive for cytoplasmic CD3, CD1a, TdT, CD2, CD7, CD5, and CD8, with partial coexpression of dimCD4. Analysis of T-cell receptor gamma polymerase chain reaction products showed clonality. T-lymphoblastic leukemia/lymphoblastic lymphoma is a very rare occurrence in the clinical setting of human immunodeficiency virus infection. It is not listed in the World Health Organization classification of lymphomas associated with human immunodeficiency virus infection. Only 4 cases of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma are reported in the current medical literature.

[Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature].

PubMed

Fayand, A; Sarrabay, G; Belot, A; Hentgen, V; Kone-Paut, I; Grateau, G; Melki, I; Georgin-Lavialle, S

2018-04-01

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.

Mannose-Binding Lectin Protein Deficiency Among Patients with Primary Immunodeficiency Disease Receiving IVIG Therapy.

PubMed

Azizi, Gholamreza; Kiaee, Fatemeh; Yaslianifard, Somaye; Rafiemanesh, Hosein; Mohammadikhajehdehi, Sara; Mohammadi, Hamed; Miresmaeeli, Seyed Sakineh; Pour, Leila H; Poor Heravi, Sina Abdolrahim; Sharifi, Laleh; Yazdani, Reza; Abolhassani, Hassan; Aghamohammadi, Asghar

2018-02-13

Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of the immune system are defective. Immunoglobulin replacement therapy is the mainstay of treatment for patients with impaired antibody production. However, recurrent infections would continue to occur in some patients due to the other high frequent concomitant defects, such as mannose-binding lectin (MBL) deficiency. A total of 51 PID patients participated in this cross-sectional study. A detailed questionnaire was completed by interviewing patients in order to record demographic, clinical and laboratory data. The levels of MBL were determined in the serums of patients by a sandwich enzyme-linked immunosorbent assay (ELISA) technique. MBL deficiency was found in 29.4% of cases; 11.8% patients had mild, 3.9% patients had moderate and 13.7% patients had severe MBL deficiency. In patients with MBL deficiency, the rate of meningitis, sepsis, pneumonia, and otitis media was higher than patients with normal MBL levels. Immunoglobulin replacement therapy reduced the rate of infectious complications in PID patients; however, these reductions were more apparent in patients with normal MBL levels than patients with MBL deficiency. Antibody deficient patients with a concomitant immune defect in MBL production have higher rates of recurrent infections despite receiving Immunoglobulin replacement therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Blastocystis, an unrecognized parasite: an overview of pathogenesis and diagnosis.

PubMed

Wawrzyniak, Ivan; Poirier, Philippe; Viscogliosi, Eric; Dionigia, Meloni; Texier, Catherine; Delbac, Frédéric; Alaoui, Hicham El

2013-10-01

Blastocystis sp. is among the few enteric parasites with a prevalence that often exceeds 5% in the general population of industrialized countries and can reach 30-60% in developing countries. This parasite is frequently found in people who are immunocompromised (patients with human immunodeficiency virus/acquired immunodeficiency syndrome or cancer) and a higher risk of Blastocystis sp. infection has been found in people with close animal contact. Such prevalence in the human population and the zoonotic potential naturally raise questions about the impact of these parasites on public health and has increased interest in this area. Recent in vitro and in vivo studies have shed new light on the pathogenic power of this parasite, suggesting that Blastocystis sp. infection is associated with a variety of gastrointestinal disorders, may play a significant role in irritable bowel syndrome, and may be linked with cutaneous lesions (urticaria). Despite recent significant advances in the knowledge of the extensive genetic diversity of this species, the identification of extracellular proteases as virulence factors and the publication of one isolate genome, many aspects of the biology of Blastocystis sp. remain poorly investigated. In this review, we investigate several biological aspects of Blastocystis sp. (diversity and epidemiology, diagnosis tools and pathophysiology). These data pave the way for the following challenges concerning Blastocystis sp. research: deciphering key biological mechanisms and pathways of this parasite and clarification of its clinical impact in humans.

Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.

PubMed

Wallace, J M; Hannah, J B

1988-08-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series.

Pulmonary Disease at Autopsy in Patients With the Acquired Immunodeficiency Syndrome

PubMed Central

Wallace, Jeanne M.; Hannah, James B.

1988-01-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series. PMID:3266812

Increased Intrasubject Variability in Response Time in Youths with Bipolar Disorder and At-Risk Family Members

ERIC Educational Resources Information Center

Brotman, Melissa A.; Rooney, Melissa H.; Skup, Martha; Pine, Daniel S.; Leibenluft, Ellen

2009-01-01

Intrasubject variability in response time (ISV-RT) was higher in youths with bipolar disorder (BD) and those with first-degree relatives with BD compared to youths without BD. ISV-RT may be a risk marker for BD.

Predictors of premature discontinuation of outpatient treatment after discharge of patients with posttraumatic stress disorder.

PubMed

Wang, Hee Ryung; Woo, Young Sup; Jun, Tae-Youn; Bahk, Won-Myong

2015-01-01

This study aimed to examine the sociodemographic and disease-related variables associated with the premature discontinuation of psychiatric outpatient treatment after discharge among patients with noncombat-related posttraumatic stress disorder. We retrospectively reviewed the medical records of patients who were discharged with a diagnosis of posttraumatic stress disorder. Fifty-five percent of subjects (57/104) prematurely discontinued outpatient treatment within 6 months of discharge. Comparing sociodemographic variables between the 6-month non-follow-up group and 6-month follow-up group, there were no variables that differed between the two groups. However, comparing disease-related variables, the 6-month follow-up group showed a longer hospitalization duration and higher Global Assessment of Function score at discharge. The logistic regression analysis showed that a shorter duration of hospitalization predicted premature discontinuation of outpatient treatment within 6 months of discharge. The duration of psychiatric hospitalization for posttraumatic stress disorder appeared to influence the premature discontinuation of outpatient treatment after discharge.

amamutdb.no: A relational database for MAN2B1 allelic variants that compiles genotypes, clinical phenotypes, and biochemical and structural data of mutant MAN2B1 in α-mannosidosis.

PubMed

Riise Stensland, Hilde Monica Frostad; Frantzen, Gabrio; Kuokkanen, Elina; Buvang, Elisabeth Kjeldsen; Klenow, Helle Bagterp; Heikinheimo, Pirkko; Malm, Dag; Nilssen, Øivind

2015-06-01

α-Mannosidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the MAN2B1 gene, encoding lysosomal α-mannosidase. The disorder is characterized by a range of clinical phenotypes of which the major manifestations are mental impairment, hearing impairment, skeletal changes, and immunodeficiency. Here, we report an α-mannosidosis mutation database, amamutdb.no, which has been constructed as a publicly accessible online resource for recording and analyzing MAN2B1 variants (http://amamutdb.no). Our aim has been to offer structured and relational information on MAN2B1 mutations and genotypes along with associated clinical phenotypes. Classifying missense mutations, as pathogenic or benign, is a challenge. Therefore, they have been given special attention as we have compiled all available data that relate to their biochemical, functional, and structural properties. The α-mannosidosis mutation database is comprehensive and relational in the sense that information can be retrieved and compiled across datasets; hence, it will facilitate diagnostics and increase our understanding of the clinical and molecular aspects of α-mannosidosis. We believe that the amamutdb.no structure and architecture will be applicable for the development of databases for any monogenic disorder. © 2015 WILEY PERIODICALS, INC.

Enzymes approved for human therapy: indications, mechanisms and adverse effects.

PubMed

Baldo, Brian A

2015-02-01

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

Clinical features that identify children with primary immunodeficiency diseases.

PubMed

Subbarayan, Anbezhil; Colarusso, Gloria; Hughes, Stephen M; Gennery, Andrew R; Slatter, Mary; Cant, Andrew J; Arkwright, Peter D

2011-05-01

The 10 warning signs of primary immunodeficiency diseases (PID) have been promoted by various organizations in Europe and the United States to predict PID. However, the ability of these warning signs to identify children with PID has not been rigorously tested. The main goal of this study was to determine the effectiveness of these 10 warning signs in predicting defined PID among children who presented to 2 tertiary pediatric immunodeficiency centers in the north of England. A retrospective survey of 563 children who presented to 2 pediatric immunodeficiency centers was undertaken. The clinical records of 430 patients with a defined PID and 133 patients for whom detailed investigations failed to establish a specific PID were reviewed. Overall, 96% of the children with PID were referred by hospital clinicians. The strongest identifiers of PID were a family history of immunodeficiency disease in addition to use of intravenous antibiotics for sepsis in children with neutrophil PID and failure to thrive in children with T-lymphocyte PID. With these 3 signs, 96% of patients with neutrophil and complement deficiencies and 89% of children with T-lymphocyte immunodeficiencies could be identified correctly. Family history was the only warning sign that identified children with B-lymphocyte PID. PID awareness initiatives should be targeted at hospital pediatricians and families with a history of PID rather than the general public. Our results provide the general pediatrician with a simple refinement of 10 warning signs for identifying children with underlying immunodeficiency diseases.

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

PubMed

Bayes, Adam; Graham, Rebecca K; Parker, Gordon B; McCraw, Stacey

2018-06-01

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene therapy for immune disorders: good news tempered by bad news.

PubMed

Puck, Jennifer M; Malech, Harry L

2006-04-01

After a dozen years of human gene therapy trials characterized by minimal gene correction and disappointing clinical impact, the field of gene therapy received some good news in 2000. Infants with X-linked severe combined immunodeficiency who received retroviral gene addition to cells from their bone marrow developed impressive immune reconstitution. During the following 2 years, additional patients were treated and the news was even better-babies receiving gene therapy had sustained T-cell production and in several cases developed better cell function than most patients treated with standard bone marrow transplants. Unfortunately, bad news followed. Three of the patients experienced leukemic T-cell expansions, found to be associated with retroviral insertions into genomic DNA. Where does the field stand today?

Genetic modification of lymphocytes by retrovirus-based vectors.

PubMed

Suerth, Julia D; Schambach, Axel; Baum, Christopher

2012-10-01

The genetic modification of lymphocytes is an important topic in the emerging field of gene therapy. Many clinical trials targeting immunodeficiency syndromes or cancer have shown therapeutic benefit; further applications address inflammatory and infectious disorders. Retroviral vector development requires a detailed understanding of the interactions with the host. Most researchers have used simple gammaretroviral vectors to modify lymphocytes, either directly or via hematopoietic stem and progenitor cells. Lentiviral, spumaviral (foamyviral) and alpharetroviral vectors were designed to reduce the necessity for cell stimulation and to utilize potentially safer integration properties. Novel surface modifications (pseudotyping) and transgenes, built using synthetic components, expand the retroviral toolbox, altogether promising increased specificity and potency. Product consistency will be an important criterion for routine clinical use. Copyright © 2012. Published by Elsevier Ltd.

Infectious mononucleosis.

PubMed

Cozad, J

1996-03-01

Infectious mononucleosis is an acute, self-limiting, nonneoplastic lymphoreticular proliferative disorder characterized by peripheral lymphocytosis and circulating atypical lymphocytes. Epstein-Barr virus is the causative agent in 90% of cases. Highest incidence is in the 15- to 25-year-old age-group, with 1% to 3% of all college students in the United States affected each year. Clinical manifestations vary according to age at presentation. Incubation period is 4 to 7 weeks. Diagnosis is primarily made with the monospot test but may include throat culture and complete blood count with differential. Cytomegalovirus and human immunodeficiency virus are among the many other conditions that may present initially as infectious mononucleosis. Treatment is supportive with prevention of complications as the goal; good personal hygiene and avoidance of contact sports should be stressed.