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

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.

Infectious and Non-infectious Etiologies of Cardiovascular Disease in Human Immunodeficiency Virus Infection.

PubMed

Chastain, Daniel B; King, Travis S; Stover, Kayla R

2016-01-01

Increasing rates of HIV have been observed in women, African Americans, and Hispanics, particularly those residing in rural areas of the United States. Although cardiovascular (CV) complications in patients infected with human immunodeficiency virus (HIV) have significantly decreased following the introduction of antiretroviral therapy on a global scale, in many rural areas, residents face geographic, social, and cultural barriers that result in decreased access to care. Despite the advancements to combat the disease, many patients in these medically underserved areas are not linked to care, and fewer than half achieve viral suppression. Databases were systematically searched for peer-reviewed publications reporting infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Relevant articles cited in the retrieved publications were also reviewed for inclusion. A variety of outcomes studies and literature reviews were included in the analysis. Relevant literature discussed the manifestations, diagnosis, treatment, and outcomes of infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. In these medically underserved areas, it is vital that clinicians are knowledgeable in the manifestations, diagnosis, and treatment of CV complications in patients with untreated HIV. This review summarizes the epidemiology and causes of CV complications associated with untreated HIV and provide recommendations for management of these complications.

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.

Feline Immunodeficiency Virus in South America

PubMed Central

Teixeira, Bruno M.; Hagiwara, Mitika K.; Cruz, Juliano C. M.; Hosie, Margaret J.

2012-01-01

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America. PMID:22590677

Feline immunodeficiency virus in South America.

PubMed

Teixeira, Bruno M; Hagiwara, Mitika K; Cruz, Juliano C M; Hosie, Margaret J

2012-03-01

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.

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.

Immunophenotypic characterization of the cutaneous exanthem of SIV-infected rhesus monkeys. Apposition of degenerative Langerhans cells and cytotoxic lymphocytes during the development of acquired immunodeficiency syndrome.

PubMed Central

Ringler, D. J.; Hancock, W. W.; King, N. W.; Letvin, N. L.; Daniel, M. D.; Desrosiers, R. C.; Murphy, G. F.

1987-01-01

A T-cell tropic retrovirus, simian immunodeficiency virus (SIV), has recently been isolated from immunodeficient rhesus monkeys. This virus has remarkable similarities to human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome. Subsequent studies of simian infection with SIV have shown it to be a relevant animal model for studying the pathogenesis of AIDS in man. In both HIV-infected humans and SIV-infected monkeys, a cutaneous maculopapular eruption has been described. To date, the pathogenesis and possible relationship of these exanthema to the evolution of systemic immunosuppression have remained obscure. In this study, the mononuclear cell infiltrates that characterize skin rashes of SIV-infected rhesus monkeys were found to be composed predominantly of cells with phenotypic characteristics of cytotoxic/suppressor (T8+) lymphocytes and natural killer cells. Many of these cells expressed membrane-bound interleukin-2 receptor molecules. Double labeling and immunoelectron microscopy revealed these cells in direct contact with degenerative Langerhans cells within the epidermis and dermis. These observations suggest that the cutaneous rash associated with SIV infection may be the consequence of target cell injury of Langerhans cells by effector cells with cytotoxic potential. Images Figure 1 Figure 2 Figure 3 PMID:3030113

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

XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus.

PubMed

Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J

2014-04-03

Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.

Fighting against acquired immunodeficiency syndrome with Chinese medicine: a perspective from China.

PubMed

Tang, Yan-li; Wang, Jie

2011-05-01

Continuing expansion of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) pandemic has been recognized as an exceptional challenge to global health. Taking highly active antiretroviral treatment (HAART), a confirmed effective treatment, has its limitations. While a much cheaper and potential treatment-the Chinese medicine (CM) has not been paid enough attention from the worldwide. We explained the CM viewpoints about pathology and etiology to answer some questions about whether and how CM can treat AIDS. Some herbal formulae and their targeted patterns and common symptoms were also introduced. Chinese government has realized the important role of CM as an independent therapy for early management, bolstering immune-system functions depressed by HIV, and has funded large randomized double-blind controlled clinical trials to more accurately assess the benefits, and valued the fundamental research to establish a quantitative standardization of pattern diagnosis. Researchers of CM are looking for cooperation with all the world's top experts in the areas of AIDS and immunity to strive for victories in the fight against AIDS.

Survival and predictors of death among primary immunodeficient patients: a registry-based study.

PubMed

Al-Herz, Waleed; Moussa, Mohamed A A

2012-06-01

The aims of this study were to investigate survival among patients with primary immunodeficiency disorders (PID) in Kuwait and to determine whether certain variables were associated with increased risk of death. The data of 176 patients (98 males and 78 females) were extracted from the Kuwait National Primary Immunodeficiency Disorders Registry and the observation period was from January 2004 to July 2011. The distribution of the reported patients was combined T- and B-cell immunodeficiencies (30.1%), predominantly antibody immunodeficiency (19.9%), other well-defined immunodeficiencies (25%), diseases of immune dysregulation (14.8%), congenital defects of phagocyte number, function or both (6.25%), and complement deficiencies (4.0%). In a total of 619.1 patient-years at risk, 48 patients died (mortality incidence rate 77.53 per 1,000 person-years). The overall survival in the studied cohort was 72.7% (72.4% for males and 73.1% for females). The most common cause of death was sepsis (46%) followed by pneumonia (29%). The probabilities that a patient survived 2, 4, and 6 years after onset of symptoms were 76%, 73%, and 69%, respectively. The variables that were found to be predictors for death are parental consanguinity, sepsis, adenovirus and CMV infections, failure to thrive, PID category, and onset age <6 months. Patients with PID have decreased probabilities of survival that are variable between PID categories. Early diagnosis and aggressive therapeutic interventions specifically of patients with history of the variables associated with increased risk of death may help increase their chance of survival.

Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity

PubMed Central

Okada, Satoshi; Puel, Anne; Casanova, Jean-Laurent; Kobayashi, Masao

2016-01-01

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC. In contrast, CMC disease (CMCD) is typically defined as CMC in patients in the absence of any other prominent clinical signs. This definition is not strict; thus, CMCD is currently used to refer to patients presenting with CMC as the main clinical phenotype. The etiology of CMCD is not related to genes that cause severe combined immunodeficiency or combined immunodeficiency, nor to genes responsible for Syndromic CMC. Four genetic etiologies, AR IL-17 receptor A, IL-17 receptor C and ACT1 deficiencies, and AD IL-17F deficiency, are reported to underlie CMCD. Each of these gene defects directly has an impact on IL-17 signaling, suggesting their nonredundant role in host mucosal immunity to Candida. Here, we review current knowledge focusing on IL-17 signaling and the genetic etiologies responsible for, and associated with, CMC. PMID:28090315

A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya.

PubMed

Malonza, I M; Tyndall, M W; Ndinya-Achola, J O; Maclean, I; Omar, S; MacDonald, K S; Perriens, J; Orle, K; Plummer, F A; Ronald, A R; Moses, S

1999-12-01

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.

Posterior Cord Syndrome and Trace Elements Deficiency as an Uncommon Presentation of Common Variable Immunodeficiency

PubMed Central

dos Santos Mota, Ananda; Morais Monteiro, Priscila; Carvalho, Angela Cristina Gouvêa; Fernandes Diniz, Barbara; Gemal Lanzieri, Pedro; Carneiro Ramos, Ricardo; Mocarzel, Luis Otavio

2017-01-01

Diarrhea is one of the most common symptoms in common variable immunodeficiency, but neurologic manifestations are rare. We presented a 50-year-old woman with recurrent diarrhea and severe weight loss that developed a posterior cord syndrome. Endoscopy found a duodenal villous blunting, intraepithelial lymphocytosis, and lack of plasma cells and magnetic resonance imaging of the spine was normal. Laboratory assays confirmed common variable immunodeficiency syndrome and showed low levels of trace elements (copper and zinc). Treatment was initiated with parenteral replacement of trace elements and intravenous human immunoglobulin and the patient improved clinically. In conclusion, physicians must be aware that gastrointestinal and neurologic disorders may be related to each other and remember to request trace elements laboratory assessment. PMID:28356913

Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: clues for possible immunosuppression-related or infectious etiology.

PubMed

Shiels, Meredith S; Engels, Eric A

2012-10-01

Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS). Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression). Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression). The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Copyright © 2012 American Cancer Society.

Trypanosoma cruzi Necrotizing Meningoencephalitis in a Venezuelan HIV+-AIDS Patient: Pathological Diagnosis Confirmed by PCR Using Formalin-Fixed- and Paraffin-Embedded-Tissues

PubMed Central

Rossi Spadafora, Marcello Salvatore; Céspedes, Ghislaine; Romero, Sandra; Fuentes, Isabel; Boada-Sucre, Alpidio A.; Cañavate, Carmen; Flores-Chávez, María

2014-01-01

Coinfections with human immunodeficiency virus (HIV) and infectious agents have been recognized since the early 90s. In the central nervous system (CNS) of HIV+ patients, parasitic protozoans like Toxoplasma gondii have been described as responsible for the space occupying lesions (SOL) developed. However, the involvement of Trypanosoma cruzi is also described but appears to be less frequent in acquired immunodeficiency syndrome (AIDS) and transplant recipients, associated with necrotizing myocarditis and neurological symptoms related to the occurrence of necrotizing pseudotumoral encephalitis (NPE) and meningoencephalitis (NME). The present work aims to present a Venezuelan case of NME associated with the coinfection of HIV and a T. cruzi-like trypanosomatid as well as its evolution and diagnosis by histopathological techniques, electron microscopy, and PCR methods using formalin-fixed- (FF-) and paraffin-embedded- (PE-) tissues. Postmortem cytological studies of leptomeninges imprints reveal the presence of trypomastigotes of Trypanosoma sp. Histopathological and electron microscopy studies allowed us to identify an amastigote stage and to reject the involvement of other opportunistic microorganisms as the etiological agent of the SOL. The definitive confirmation of T. cruzi as the etiological agent was achieved by PCR suggesting that the NME by T. cruzi was due to a reactivation of Chagas' disease. PMID:25763312

Progressive Outer Retinal Necrosis Combined with Vitreous Hemorrhage in a Patient with Acquired Immunodeficiency Syndrome

PubMed Central

You, Yong Sung; Lee, Sung Jin; Lee, Sung Ho; Park, Chang Hyun

2007-01-01

Purpose To describe an unusual case of rapidly progressive outer retinal necrosis (PORN) with vitreous hemorrhage in a 41-year-old woman with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from what was probably varicellar-zoster virus combined with cytomegalovirus (CMV) and herpes simplex type 1,2, as proven by the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Methods This study is a case report detailing clinical follow-up and an aqueous humor test by PCR-RFLP. Results The deep, white retinal lesions coalesced and progressively expanded in a circumferential manner, with sparing of the perivascular retina. However, retinal and vitreous hemorrhages, unusual findings for PORN, could be noted around the optic nerve. Varicellar-zoster virus (VZV), cytomegalovirus (CMV), and herpes simplex types 1,2 (HSV-1,2) were detected in the aqueous humor by PCR. Conclusions PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, concurrent or combined etiologic agents can include HSV-1, HSV-2, and CMV in AIDS patients. Therefore, combined antiviral therapy with acyclovir and ganciclovir could be more reasonable as an initial therapy. PMID:17460434

Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity.

PubMed

Lonni, Sara; Chalmers, James D; Goeminne, Pieter C; McDonnell, Melissa J; Dimakou, Katerina; De Soyza, Anthony; Polverino, Eva; Van de Kerkhove, Charlotte; Rutherford, Robert; Davison, John; Rosales, Edmundo; Pesci, Alberto; Restrepo, Marcos I; Torres, Antoni; Aliberti, Stefano

2015-12-01

Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.

Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.

PubMed

Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp

2017-09-25

Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

Infectious encephalitis: Management without etiological diagnosis 48hours after onset.

PubMed

Fillatre, P; Crabol, Y; Morand, P; Piroth, L; Honnorat, J; Stahl, J P; Lecuit, M

2017-05-01

The etiological diagnosis of infectious encephalitis is often not established 48hours after onset. We aimed to review existing literature data before providing management guidelines. We performed a literature search on PubMed using filters such as "since 01/01/2000", "human", "adults", "English or French", and "clinical trial/review/guidelines". We also used the Mesh search terms "encephalitis/therapy" and "encephalitis/diagnosis". With Mesh search terms "encephalitis/therapy" and "encephalitis/diagnosis", we retrieved 223 and 258 articles, respectively. With search terms "encephalitis and corticosteroid", we identified 38 articles, and with "encephalitis and doxycycline" without the above-mentioned filters we identified 85 articles. A total of 210 articles were included in the analysis. Etiological investigations must focus on recent travels, animal exposures, age, immunodeficiency, neurological damage characteristics, and potential extra-neurological signs. The interest of a diagnosis of encephalitis for which there is no specific treatment is also to discontinue any empirical treatments initially prescribed. Physicians must consider and search for autoimmune encephalitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The use of molindone in the treatment of psychotic and delirious patients infected with the human immunodeficiency virus. Case reports.

PubMed

Fernandez, F; Levy, J K

1993-01-01

Four patients with HIV infection and psychosis from various etiologies, refractory to standard treatments, and suffering from severe extrapyramidal symptoms (EPS), had a marked beneficial response to molindone. There was significant control of neuropsychiatric dysfunction without major adverse side effects. The results suggest that further evaluation is warranted of the use of molindone in treating severely ill, psychotic, or delirious HIV-infected patients.

Etiology of Non–Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity

PubMed Central

Lonni, Sara; Chalmers, James D.; Goeminne, Pieter C.; McDonnell, Melissa J.; Dimakou, Katerina; De Soyza, Anthony; Polverino, Eva; Van de Kerkhove, Charlotte; Rutherford, Robert; Davison, John; Rosales, Edmundo; Pesci, Alberto; Restrepo, Marcos I.; Torres, Antoni

2015-01-01

Rationale: Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. Objectives: The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. Methods: We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Measurements and Main Results: Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient’s management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease–related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Conclusions: Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease. PMID:26431397

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)

Etiology of Bronchiectasis in a Cohort of 2047 Patients. An Analysis of the Spanish Historical Bronchiectasis Registry.

PubMed

Olveira, Casilda; Padilla, Alicia; Martínez-García, Miguel-Ángel; de la Rosa, David; Girón, Rosa-María; Vendrell, Montserrat; Máiz, Luis; Borderías, Luis; Polverino, Eva; Martínez-Moragón, Eva; Rajas, Olga; Casas, Francisco; Cordovilla, Rosa; de Gracia, Javier

2017-07-01

Bronchiectasis is caused by many diseases. Establishing its etiology is important for clinical and prognostic reasons. The aim of this study was to evaluate the etiology of bronchiectasis in a large patient sample and its possible relationship with demographic, clinical or severity factors, and to analyze differences between idiopathic disease, post-infectious disease, and disease caused by other factors. Multicenter, cross-sectional study of the SEPAR Spanish Historical Registry (RHEBQ-SEPAR). Adult patients with bronchiectasis followed by pulmonologists were included prospectively. Etiological studies were based on guidelines and standardized diagnostic tests included in the register, which were later included in the SEPAR guidelines on bronchiectasis. A total of 2,047 patients from 36 Spanish hospitals were analyzed. Mean age was 64.9years and 54.9% were women. Etiology was identified in 75.8% of cases (post-Infection: 30%; cystic fibrosis: 12.5%; immunodeficiencies: 9.4%; COPD: 7.8%; asthma: 5.4%; ciliary dyskinesia: 2.9%, and systemic diseases: 1.4%). The different etiologies presented different demographic, clinical, and microbiological factors. Post-infectious bronchiectasis and bronchiectasis caused by COPD and asthma were associated with an increased risk of poorer lung function. Patients with post-infectious bronchiectasis were older and were diagnosed later. Idiopathic bronchiectasis was more common in female non-smokers and was associated with better lung function, a higher body mass index, and a lower rate of Pseudomonas aeruginosa than bronchiectasis of known etiology. The etiology of bronchiectasis was identified in a large proportion of patients included in the RHEBQ-SEPAR registry. Different phenotypes associated with different causes could be identified. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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

Clinical Manifestations and the Natural History of HIV Infection in Adults

PubMed Central

Piot, Peter; Colebunders, Robert

1987-01-01

The clinical expression of infection with the human immunodeficiency virus (HIV) appears increasingly complex. It includes manifestations due to opportunistic diseases, as well as illness directly caused by HIV itself. Neurologic disease may include involvement of the brain, spinal cord and peripheral nerves and is probably directly caused by HIV, as is lymphocytic interstitial pneumonia. The etiology of the chronic diarrhea and a papular pruritic skin eruption associated with HIV infection is unclear. Between 2% and 8% of HIV-infected persons progress to the acquired immunodeficiency syndrome (AIDS) per year, with no apparent decrease in the rate of disease progression over time. A chronically activated state secondary to chronic microbial antigenic exposure may increase both the susceptibility to HIV infection and development of disease. Increased HIV gene expression, followed by persistent antigenemia, appear to be triggering factors in clinical deterioration. The role, if any, of environmental and/or genetic cofactors remains unclear. Images PMID:3433753

[Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

PubMed

Kotyla, Przemysław; Kucharz, Eugeniusz J

2012-01-01

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

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

Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.

PubMed

Li, Jin; Jørgensen, Silje F; Maggadottir, S Melkorka; Bakay, Marina; Warnatz, Klaus; Glessner, Joseph; Pandey, Rahul; Salzer, Ulrich; Schmidt, Reinhold E; Perez, Elena; Resnick, Elena; Goldacker, Sigune; Buchta, Mary; Witte, Torsten; Padyukov, Leonid; Videm, Vibeke; Folseraas, Trine; Atschekzei, Faranaz; Elder, James T; Nair, Rajan P; Winkelmann, Juliane; Gieger, Christian; Nöthen, Markus M; Büning, Carsten; Brand, Stephan; Sullivan, Kathleen E; Orange, Jordan S; Fevang, Børre; Schreiber, Stefan; Lieb, Wolfgang; Aukrust, Pål; Chapel, Helen; Cunningham-Rundles, Charlotte; Franke, Andre; Karlsen, Tom H; Grimbacher, Bodo; Hakonarson, Hakon; Hammarström, Lennart; Ellinghaus, Eva

2015-04-20

Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

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.

Current and Emerging Antivirals for the Treatment of Cytomegalovirus (CMV) Retinitis: an Update on Recent Patents

PubMed Central

Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Mitra, Ashim K.

2015-01-01

Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic complication and a serious cause of vision loss in immunocompromised patients. Even though, a rise in human immunodeficiency virus (HIV) infected individuals seems to be a major factor responsible for the prevalence of CMV retinitis, the introduction of highly active antiretroviral therapy (HAART) significantly reduced the incidence and severity of CMV retinitis. Thorough evaluation of the patient’s immune status and an exact classification of the retinal lesions may provide better understanding of the disease etiology, which would be necessary for optimizing the treatment conditions. Current drugs such as ganciclovir, valganciclovir, cidofovir and foscarnet have been highly active against CMV, but prolonged therapy with these approved drugs is associated with dose-limiting toxicities thus limiting their utility. Moreover development of drug-resistant mutants has been observed particularly in patients with acquired immunodeficiency syndrome (AIDS). Continuous efforts by researchers in the industry and academia have led to the development of newer candidates with enhanced antiviral efficacy and apparently minimal side effects. These novel compounds can suppress viral replication and prevent reactivation in the target population. Though some of the novel therapeutics possess potent viral inhibitory activity, these compounds are still in stages of clinical development and yet to be approved. This review provides an overview of disease etiology, existing anti-CMV drugs, advances in emerging therapeutics in clinical development and related recent patents for the treatment of CMV retinitis. PMID:22044356

[Esophageal pathology in patients with the AIDS virus. Etiology and diagnosis].

PubMed

Varsky, C G; Yahni, V D; Freire, M C; Patrizio, E; Balbo, V; Benetucci, J; Boffi, A; Mattoni, R A; Luis; Alicia, M

1991-01-01

From 180 patients infected with human immunodeficiency virus (HIV) and followed-up for one year, 17 cases (9.44%) were referred to detect oesophageal pathology. They were prospectively analyzed through fibroscopy, radiology, biopsies for histopathology, virology and mycology and brush cytology. Most frequent symptoms were dysphagia. Odynophagia and retrosternal pain, usually associated, and not providing an accurate diagnostic clue. The most common causes of symptoms were oesophageal candidiasis (47.70%), and herpetic ulcers (23.52%) caused by herpes simplex virus (HSV) type 2. Reflux pathology was also found (11.76%). Cytomegalovirus, other opportunistic infections and tumors were not detected. Seven (64%) of the eleven patients with oesophageal candidiasis also had oral involvement. Four (66%) of six oesophageal ulcers were herpetic; two of them (50%) showed oral ulcers too, and one (25%) had perioral herpetic blisters. Almost in every case endoscopic features allowed diagnosis. Endoscopy in candidiasis showed isolated or confluent white plaques of variable grade. Herpetic ulcers, alone or multiple, were deep with slightly elevated borders. Radiology yielded a poor diagnostic profit (50%), specially in case of multiple lesions. Cytology was highly specific and sensitive (both 90.9%) and suggested viral etiology in 100% of HSV patients. Histopathology was less sensitive than endoscopy and cytology (73% in candida and one HSV non-ulcer case). Both, cytology and histopathology showed koilocytosis in herpetic virus infected patients. The studies performed allowed to change the HIV disease stage in ten patients (62.5%) and to diagnose AIDS in seven (43.75%). In every case medical behavior was oriented or changed by these studies.

A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.

PubMed

Ducancelle, Alexandra; Leroy, Vincent; Vergniol, Julien; Sturm, Nathalie; Le Bail, Brigitte; Zarski, Jean Pierre; Nguyen Khac, Eric; Salmon, Dominique; de Ledinghen, Victor; Calès, Paul

2017-08-01

International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

PubMed Central

Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

2016-01-01

The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

Identification and selection of cases and controls in the Pneumonia Etiology Research for Child Health project.

PubMed

Deloria-Knoll, Maria; Feikin, Daniel R; Scott, J Anthony G; O'Brien, Katherine L; DeLuca, Andrea N; Driscoll, Amanda J; Levine, Orin S

2012-04-01

Methods for the identification and selection of patients (cases) with severe or very severe pneumonia and controls for the Pneumonia Etiology Research for Child Health (PERCH) project were needed. Issues considered include eligibility criteria and sampling strategies, whether to enroll hospital or community controls, whether to exclude controls with upper respiratory tract infection (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH ultimately decided to enroll community controls and an additional human immunodeficiency virus (HIV)-infected control group at high HIV-prevalence sites matched on age and enrollment date of cases; controls with symptoms of URTI or nonsevere pneumonia will not be excluded. Systematic sampling of cases (when necessary) and random sampling of controls will be implemented. For each issue, we present the options that were considered, the advantages and disadvantages of each, the rationale for the methods selected for PERCH, and remaining implications and limitations.

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.

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.

[30 years since the first AIDS cases were reported: history and the present. Part I].

PubMed

Brůcková, Marie

2012-05-01

The 30-year natural history of AIDS disease is presented from the first clinical cases reported in 1981 to the identification of the HIV as the etiological agent of the disease. The priority dispute between Robert C. Gallo and Luc Montagnier over the discovery of the human immunodeficiency virus is briefly addressed. The final confirmation of the French priority was provided by the fact that the Nobel Prize in Medicine 2008 was awarded to Luc Montagnier and Francoise Barré--Sinoussi from the Pasteur Institute in Paris.

Spoken language outcomes after hemispherectomy: factoring in etiology.

PubMed

Curtiss, S; de Bode, S; Mathern, G W

2001-12-01

We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology. Copyright 2001 Elsevier Science.

Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome

PubMed Central

Handley, Scott; Thackray, Larissa B.; Zhao, Guoyan; Presti, Rachel; Miller, Andrew; Droit, Lindsay; Abbink, Peter; Maxfield, Lori F.; Kambal, Amal; Duan, Erning; Stanley, Kelly; Kramer, Joshua; Macri, Sheila C.; Permar, Sallie R.; Schmitz, Joern E.; Mansfield, Keith; Brenchley, Jason M.; Veazey, Ronald S.; Stappenbeck, Thaddeus S.; Wang, David; Barouch, Dan H.; Virgin, Herbert W.

2012-01-01

SUMMARY Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not non-pathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis. PMID:23063120

Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States.

PubMed

Shebl, Fatma M; Bhatia, Kishor; Engels, Eric A

2010-05-15

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N = 519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N = 43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N = 39 cases), risks were elevated for both keratinizing and nonkeratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7 and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important.

Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

PubMed

Lewis, J H; Sundeen, J T; Simon, G L; Schulof, R S; Wand, G S; Gelfand, R L; Miller, H; Garrett, C T; Jannotta, F S; Orenstein, J M

1985-02-01

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.

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.

Conducting systematic reviews of association (etiology): The Joanna Briggs Institute's approach.

PubMed

Moola, Sandeep; Munn, Zachary; Sears, Kim; Sfetcu, Raluca; Currie, Marian; Lisy, Karolina; Tufanaru, Catalin; Qureshi, Rubab; Mattis, Patrick; Mu, Peifan

2015-09-01

The systematic review of evidence is the research method which underpins the traditional approach to evidence-based healthcare. There is currently no uniform methodology for conducting a systematic review of association (etiology). This study outlines and describes the Joanna Briggs Institute's approach and guidance for synthesizing evidence related to association with a predominant focus on etiology and contributes to the emerging field of systematic review methodologies. It should be noted that questions of association typically address etiological or prognostic issues.The systematic review of studies to answer questions of etiology follows the same basic principles of systematic review of other types of data. An a priori protocol must inform the conduct of the systematic review, comprehensive searching must be performed and critical appraisal of retrieved studies must be carried out.The overarching objective of systematic reviews of etiology is to identify and synthesize the best available evidence on the factors of interest that are associated with a particular disease or outcome. The traditional PICO (population, interventions, comparators and outcomes) format for systematic reviews of effects does not align with questions relating to etiology. A systematic review of etiology should include the following aspects: population, exposure of interest (independent variable) and outcome (dependent variable).Studies of etiology are predominantly explanatory or predictive. The objective of reviews of explanatory or predictive studies is to contribute to, and improve our understanding of, the relationship of health-related events or outcomes by examining the association between variables. When interpreting possible associations between variables based on observational study data, caution must be exercised due to the likely presence of confounding variables or moderators that may impact on the results.As with all systematic reviews, there are various approaches to present the results, including a narrative, graphical or tabular summary, or meta-analysis. When meta-analysis is not possible, a set of alternative methods for synthesizing research is available. On the basis of the research question and objectives, narrative, tabular and/or visual approaches can be used for data synthesis. There are some special considerations when conducting meta-analysis for questions related to risk and correlation. These include, but are not limited to, causal inference.Systematic review and meta-analysis of studies related to etiology is an emerging methodology in the field of evidence synthesis. These reviews can provide useful information for healthcare professionals and policymakers on the burden of disease. The standardized Joanna Briggs Institute approach offers a rigorous and transparent method to conduct reviews of etiology.

Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection.

PubMed Central

Wasserheit, J N

1994-01-01

The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135

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.

A Hypomorphic RAG1 Mutation Resulting in a Phenotype Resembling Common Variable Immunodeficiency

PubMed Central

Abolhassani, Hassan; Wang, Ning; Aghamohammadi, Asghar; Rezaei, Nima; Lee, Yu Nee; Frugoni, Francesco; Notrangelo, Luigi D.; Pan-Hammarström, Qiang; Hammarström, Lennart

2014-01-01

Background RAG1 deficiency presents a varied spectrum of combined immunodeficiency, ranging from a T−B−NK+type of disease to a T+B+NK+ phenotype. Objective To assess the genetic background of common variable immunodeficiency (CVID) patients. Methods A patient diagnosed with CVID, who was born in a consanguineous family and thus would be expected to show an autosomal recessive inheritance, was subjected to clinical evaluation, immunological assays, homozygosity gene mapping, exome sequencing, Sanger sequencing and functional analysis. Results The 14-year-old patient, who suffered from liver granuloma, extranodal marginal zone B cell lymphoma and autoimmune neutropenia, is presented with a clinical picture resembling CVID. Genetic analysis of this patient showed a homozygous hypomorphic RAG1 mutation (c.1073 G>A, p.C358Y) with a residual functional capacity of 48% of wild-type protein. Conclusion Our finding broadens the range of disorders associated with RAG1 mutations and may have important therapeutic implications. PMID:24996264

A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

PubMed

Ballew, Bari J; Joseph, Vijai; De, Saurav; Sarek, Grzegorz; Vannier, Jean-Baptiste; Stracker, Travis; Schrader, Kasmintan A; Small, Trudy N; O'Reilly, Richard; Manschreck, Chris; Harlan Fleischut, Megan M; Zhang, Liying; Sullivan, John; Stratton, Kelly; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Alter, Blanche P; Boland, Joseph; Burdett, Laurie; Offit, Kenneth; Boulton, Simon J; Savage, Sharon A; Petrini, John H J

2013-08-01

Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.

A Recessive Founder Mutation in Regulator of Telomere Elongation Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of Hoyeraal Hreidarsson Syndrome

PubMed Central

Ballew, Bari J.; Joseph, Vijai; De, Saurav; Sarek, Grzegorz; Vannier, Jean-Baptiste; Stracker, Travis; Schrader, Kasmintan A.; Small, Trudy N.; O'Reilly, Richard; Manschreck, Chris; Harlan Fleischut, Megan M.; Zhang, Liying; Sullivan, John; Stratton, Kelly; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Alter, Blanche P.; Boland, Joseph; Burdett, Laurie; Offit, Kenneth; Boulton, Simon J.

2013-01-01

Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1. PMID:24009516

University of North Carolina Caries Risk Assessment Study: comparisons of high risk prediction, any risk prediction, and any risk etiologic models.

PubMed

Beck, J D; Weintraub, J A; Disney, J A; Graves, R C; Stamm, J W; Kaste, L M; Bohannan, H M

1992-12-01

The purpose of this analysis is to compare three different statistical models for predicting children likely to be at risk of developing dental caries over a 3-yr period. Data are based on 4117 children who participated in the University of North Carolina Caries Risk Assessment Study, a longitudinal study conducted in the Aiken, South Carolina, and Portland, Maine areas. The three models differed with respect to either the types of variables included or the definition of disease outcome. The two "Prediction" models included both risk factor variables thought to cause dental caries and indicator variables that are associated with dental caries, but are not thought to be causal for the disease. The "Etiologic" model included only etiologic factors as variables. A dichotomous outcome measure--none or any 3-yr increment, was used in the "Any Risk Etiologic model" and the "Any Risk Prediction Model". Another outcome, based on a gradient measure of disease, was used in the "High Risk Prediction Model". The variables that are significant in these models vary across grades and sites, but are more consistent among the Etiologic model than the Predictor models. However, among the three sets of models, the Any Risk Prediction Models have the highest sensitivity and positive predictive values, whereas the High Risk Prediction Models have the highest specificity and negative predictive values. Considerations in determining model preference are discussed.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports.

PubMed

El Kohen, A; Planquart, X; Al Hamany, Z; Bienvenu, L; Kzadri, M; Herman, D

2001-12-01

Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman's syndrome is a rare benign disease of unknown etiology, usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-Rosai-Dorfman's syndrome are discussed.

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.

Prevalence of Primary Immunodeficiency in Korea

PubMed Central

Rhim, Jung Woo; Kim, Kyung Hyo; Kim, Dong Soo; Kim, Bong Seong; Kim, Jung Soo; Kim, Chang Hwi; Kim, Hwang Min; Park, Hee Ju; Pai, Ki Soo; Son, Byong Kwan; Shin, Kyung Sue; Oh, Moo Young; Woo, Young Jong; Yoo, Young; Lee, Kun Soo; Lee, Kyung Yil; Lee, Chong Guk; Lee, Joon Sung; Chung, Eun Hee; Choi, Eun Hwa; Hahn, Youn Soo; Park, Hyun Young

2012-01-01

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea. PMID:22787376

Human retroviruses: their role in cancer.

PubMed

Blattner, W A

1999-01-01

Viruses are etiologically linked to approximately 20% of all malignancies worldwide. Retroviruses account for approximately 8%-10% of the total. For human T-cell leukemia virus 1 (HTLV-I), the viral regulatory tax gene product is responsible for enhanced transcription of viral and cellular genes that promote cell growth by stimulating various growth factors and through dysregulation of cellular regulatory suppressor genes, such as p53. After a long latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and over half of the adult lymphoid malignancies in endemic areas. Human immunodeficiency virus 1 (HIV-1) accounts for a significant cancer burden, and its transactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homosexual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly active antiretroviral therapy (HAART) could be due to suppression of HIV-1 tat. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodeficiency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgkin's lymphoma is also associated with HIV infection but at a lower risk. Human papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.

Acquired immunodeficiency syndrome — an assessment of the present situation in the world: Memorandum from a WHO Meeting*

PubMed Central

1984-01-01

A consultative meeting was convened by the World Health Organization in Geneva on 22-25 November 1983 to assess the present situation of AIDS (the acquired immunodeficiency syndrome) in the world and to encourage collaboration between the different nations affected by this disease. AIDS was first reported in the USA in 1981, but probably existed there as early as 1978. Soon after its recognition in the USA, similar cases were identified in other areas of the world. In most western European countries and Canada, the epidemiological pattern is very similar to that in the United States, the majority of cases being in homosexual men. In other areas such as equatorial Africa and the Caribbean, the pattern seems to be different with no identifiable risk factors for the majority of cases. The disease is manifested by opportunistic infections and/or selected malignancies, with apparent differences in the clinical presentation between the cases in North America and Europe, on the one hand, and those in the tropics. To date there is no treatment that has significantly improved the underlying cellular immune deficiency, and the mortality is very high. The etiology of AIDS is unknown, but the epidemiological pattern is most consistent with its being caused by a transmissible agent; retroviruses come on top of the list of candidate agents. Despite the unknown etiology and the lack of laboratory diagnostic tests, sufficient information is available to permit health authorities to make recommendations that may reduce appreciably the incidence of the disease. AIDS is an important health problem in a number of countries and has international implications. Collaborative laboratory, epidemiological and clinical research between countries is needed to accelerate control efforts. In the meantime, WHO will coordinate exchange of information among countries. ImagesFig. 1 PMID:6331905

Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression.

PubMed

Pulvirenti, J J; Kerns, E; Benson, C; Lisowski, J; Demarais, P; Weinstein, R A

1996-01-01

Human immunodeficiency virus (HIV)-infected patients are at increased risk for serious and recurrent bacterial infections. We hypothesized that the degree of immunosuppression may play an important role in outcomes for HIV-seropositive patients with infective endocarditis (IE). To test our hypothesis, we retrospectively reviewed 144 cases of IE in injection drug users. One hundred two patients with documented HIV status (45 HIV-seropositive patients and 57 HIV-seronegative patients) were included in the analysis. Eleven patients (6 HIV-seropositive patients and 5 HIV-seronegative patients) died in the hospital. Staphylococcus aureus, the most common etiologic pathogen causing IE in our series, was isolated from 32 HIV-seropositive patients (71.1%) and 32 HIV-seronegative patients (56.1%). A clear inverse correlation between mortality rate and CD4 cell count was demonstrated (r = -.625; P < .001). Both univariate and multivariate analyses supported the finding of significantly higher mortality rates among patients with CD4 cell counts of < 200/mm3 than among patients with CD4 cell counts of > 500/mm3 (OR, 14.7; 95% CI, 2.64-81.9).

Salivary Gland and Nasopharyngeal Cancers in Individuals with Acquired Immunodeficiency Syndrome in United States

PubMed Central

Shebl, Fatma M.; Bhatia, Kishor; Engels, Eric A.

2009-01-01

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N=519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N=43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N=39 cases), risks were elevated for both keratinizing and non-keratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7, and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important. PMID:19810095

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

British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

PubMed

Hurst, John R; Verma, Nisha; Lowe, David; Baxendale, Helen E; Jolles, Stephen; Kelleher, Peter; Longhurst, Hilary J; Patel, Smita Y; Renzoni, Elisabetta A; Sander, Clare R; Avery, Gerard R; Babar, Judith L; Buckland, Matthew S; Burns, Siobhan; Egner, William; Gompels, Mark M; Gordins, Pavels; Haddock, Jamanda A; Hart, Simon P; Hayman, Grant R; Herriot, Richard; Hoyles, Rachel K; Huissoon, Aarnoud P; Jacob, Joseph; Nicholson, Andrew G; Rassl, Doris M; Sargur, Ravishankar B; Savic, Sinisa; Seneviratne, Suranjith L; Sheaff, Michael; Vaitla, Prashantha M; Walters, Gareth I; Whitehouse, Joanna L; Wright, Penny A; Condliffe, Alison M

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human NF-κB1 Haploinsufficiency and Epstein-Barr Virus-Induced Disease-Molecular Mechanisms and Consequences.

PubMed

Hoeger, Birgit; Serwas, Nina Kathrin; Boztug, Kaan

2017-01-01

Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein-Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease.

Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition

PubMed Central

Rodríguez-Cortez, Virginia C.; del Pino-Molina, Lucia; Rodríguez-Ubreva, Javier; Ciudad, Laura; Gómez-Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez-Gallego, Carlos; López-Granados, Eduardo; Ballestar, Esteban

2015-01-01

Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. PMID:26081581

Human NF-κB1 Haploinsufficiency and Epstein–Barr Virus-Induced Disease—Molecular Mechanisms and Consequences

PubMed Central

Hoeger, Birgit; Serwas, Nina Kathrin; Boztug, Kaan

2018-01-01

Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein–Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease. PMID:29403474

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.

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.

HIV and Bone Metabolism

PubMed Central

Ofotokun, Ighovwerha; Weitzmann, M. Neale

2013-01-01

The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the “immuno-skeletal interface.” Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART. PMID:21616037

Cancer Prevention in HIV-Infected Populations

PubMed Central

Goncalves, Priscila H.; Montezuma-Rusca, Jairo M.; Yarchoan, Robert; Uldrick, Thomas S.

2016-01-01

People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality. Tailored cancer-prevention strategies are needed for this population. In this review we describe the etiologic agents and pathogenesis of common malignancies in the setting of HIV, as well as current evidence for cancer prevention strategies and screening programs. PMID:26970136

Detection of a human intracisternal A-type retroviral particle antigenically related to HIV

NASA Technical Reports Server (NTRS)

Garry, R. F.; Fermin, C. D.; Hart, D. J.; Alexander, S. S.; Donehower, L. A.; Luo-Zhang, H.

1990-01-01

Sjogren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria.

ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency.

PubMed

Lian, Jayson; Cuk, Mario; Kahlfuss, Sascha; Kozhaya, Lina; Vaeth, Martin; Rieux-Laucat, Frédéric; Picard, Capucine; Benson, Melina J; Jakovcevic, Antonia; Bilic, Karmen; Martinac, Iva; Stathopulos, Peter; Kacskovics, Imre; Vraetz, Thomas; Speckmann, Carsten; Ehl, Stephan; Issekutz, Thomas; Unutmaz, Derya; Feske, Stefan

2017-11-16

Store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ channels is an essential signaling pathway in many cell types. Ca 2+ release-activated Ca 2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms. We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology. We performed DNA sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of peripheral blood lymphocyte populations by using flow cytometry, and histologic and ultrastructural analysis of patient tissues. We identified 3 novel autosomal recessive mutations in ORAI1 in unrelated kindreds with CID, autoimmunity, ectodermal dysplasia with anhidrosis, and muscular dysplasia. The patients were homozygous for p.V181SfsX8, p.L194P, and p.G98R mutations in the ORAI1 gene that suppressed ORAI1 protein expression and SOCE in the patients' lymphocytes and fibroblasts. In addition to impaired T-cell cytokine production, ORAI1 mutations were associated with strongly reduced numbers of invariant natural killer T and regulatory T (Treg) cells and altered composition of γδ T-cell and natural killer cell subsets. ORAI1 null mutations are associated with reduced numbers of invariant natural killer T and Treg cells that likely contribute to the patients' immunodeficiency and autoimmunity. ORAI1-deficient patients have dental enamel defects and anhidrosis, representing a new form of anhidrotic ectodermal dysplasia with immunodeficiency that is distinct from previously reported patients with anhidrotic ectodermal dysplasia with immunodeficiency caused by mutations in the nuclear factor κB signaling pathway (IKBKG and NFKBIA). Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

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.

TAFRO syndrome: current perspectives.

PubMed

Sakashita, Kentaro; Murata, Kengo; Takamori, Mikio

2018-01-01

Multicentric Castleman's disease (MCD), a distinct subtype of Castleman's disease, is a rare, nonneoplastic, lymphoproliferative disorder. Patients with MCD present with systemic symptoms and multiple lymphadenopathy. Lymph node biopsy is necessary for the diagnosis of various histological MCD patterns including hyaline vascular, plasma cell, and mixed types. Human herpesvirus 8 (HHV8) infection was identified as an important etiology of MCD among immunocompromised patients such as those positive for human immunodeficiency virus. Although HHV8-negative MCD was reported in immunocompetent patients, the underlying etiology remains unknown. Several experts speculate that MCD in immunocompetent patients might be due to proinflammatory hypercytokinemia because of infection by a virus other than HHV8, inflammation, or neoplastic disease. In 2010, a distinct variant of HHV8-negative MCD reported in Japan was characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Recent case reports and a systematic review suggest that TAFRO syndrome might have a unique pathogenesis among HHV8-negative MCD variants. This review introduces TAFRO syndrome as a subtype of HHV8-negative MCD and offers an overview of the current perspectives on this syndrome.

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.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

PubMed

Sempere, L; Palazón, J M; Sánchez-Payá, J; Pascual, S; de Madaria, E; Poveda, M J; Carnicer, F; Zapater, P; Pérez-Mateo, M

2009-04-01

to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

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

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

PubMed

van Schouwenburg, Pauline A; Davenport, Emma E; Kienzler, Anne-Kathrin; Marwah, Ishita; Wright, Benjamin; Lucas, Mary; Malinauskas, Tomas; Martin, Hilary C; Lockstone, Helen E; Cazier, Jean-Baptiste; Chapel, Helen M; Knight, Julian C; Patel, Smita Y

2015-10-01

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways. Copyright © 2015. Published by Elsevier Inc.

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.

Diketo acids derivatives as integrase inhibitors: the war against the acquired immunodeficiency syndrome.

PubMed

Henao-Mejia, Jorge; Góez, Yenny; Patiño, Pablo; Rugeles, Maria T

2006-06-01

Since the human immunodeficiency virus was identified as etiological agent of the acquired immunodeficiency syndrome, great advances have been accomplished in the therapeutic field leading to reduced morbidity and mortality among infected patients. However, the high mutation rate of the viral genome generates strains resistant to multiple drugs, pointing to the importance of finding new therapeutic targets. Among the HIV structural genes, the POL gene codes for three essential enzymes: reverse transcriptase, protease, and integrase; nineteen of the twenty drugs currently approved by the Food and Drug Administration to treat this viral infection, inhibit the reverse transcriptase and the protease. Although intense research has been carried out in this area during the last 10 years, HIV integrase inhibitors are not yet approved for clinical use; however the fact that presence of this enzyme is a sine qua non for a productive HIV life cycle joined to its unique properties makes it a promissory target for anti-HIV therapy. Many compounds have been claimed to inhibit integrase in vitro; however, few of them have proven to have antiviral activity and low cytotoxicity in cell systems. Diketoacid derivatives are the most promising integrase inhibitors so far reported. Initially discovered independently by Shionogi & Co. and the Merck Research Laboratories, these compounds are highly specific for the integrase with potent antiviral activity in vitro and in vivo, and low cytotoxicity in cell cultures. Some of these compounds have recently entered clinical trials. Due to the high relevance of integrase inhibitors, and specifically of diketoacid derivatives, we review the latest findings and patents in this important field of research.

The puzzling role of CXCR4 in human immunodeficiency virus infection.

PubMed

Vicenzi, Elisa; Liò, Pietro; Poli, Guido

2013-01-01

The human immunodeficiency virus type-1 (HIV-1) is the etiological agent of the acquired immunodeficiency syndrome (AIDS), a disease highly lethal in the absence of combination antiretroviral therapy. HIV infects CD4(+) cells of the immune system (T cells, monocyte-macrophages and dendritic cells) via interaction with a universal primary receptor, the CD4 molecule, followed by a mandatory interaction with a second receptor (co-receptor) belonging to the chemokine receptor family. Apart from some rare cases, two chemokine receptors have been evolutionarily selected to accomplish this need for HIV-1: CCR5 and CXCR4. Yet, usage of these two receptors appears to be neither casual nor simply explained by their levels of cell surface expression. While CCR5 use is the universal rule at the start of every infection regardless of the transmission route (blood-related, sexual or mother to child), CXCR4 utilization emerges later in disease coinciding with the immunological deficient phase of infection. Moreover, in most instances CXCR4 use as viral entry co-receptor is associated with maintenance of CCR5 use. Since antiviral agents preventing CCR5 utilization by the virus are already in use, while others targeting either CCR5 or CXCR4 (or both) are under investigation, understanding the biological correlates of this "asymmetrical" utilization of HIV entry co-receptors bears relevance for the clinical choice of which therapeutics should be administered to infected individuals. We will here summarize the basic knowledge and the hypotheses underlying the puzzling and yet unequivocal role of CXCR4 in HIV-1 infection.

Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

PubMed Central

Gami, Bhavna; Kubba, Faris; Ziprin, Paul

2014-01-01

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus. PMID:25288893

[Final clinical indications and etiology in 1,023 enucleations. Descriptive databank evaluation with SPSS software in variable response mode with dummy variables].

PubMed

Becker, H; Bialasiewicz, A A; Schaudig, U; Schäfer, H; von Domarus, D

2002-05-01

A new data bank developed for ophthalmopathology using a computer-generated, multidigital data code is expected to be able to accomplish complex clinicopathologic correlations of diagnoses and signs, as provided by (multiple) clinical events and histopathologically proven etiologies, and to facilitate the documentation of new data. In the ophthalmopathology laboratory 2890 eyes were examined between January 20, 1975 and December 12, 1996. The main diagnoses and patient data from this 22-year period were recorded. To facilitate the presentation of data, a 10-year period with eyes of 976 patients enucleated from December, 1986 to December, 1996 was chosen. Principal and secondary diagnoses served for establishing the data bank. The frequencies of successive histologic and clinical diagnoses were evaluated by a descriptive computing program using an SPSS-multi-response mode with dummy variables and a categorical variable listing of the software (SPSS version 10.0) classified as (a) non-filtered random, (b) filtered by multiple etiologies, and (c) filtered by multiple events. The principal groups (e.g., histologic diagnoses concerning etiology) and subgroups (e.g., trauma, neoplasia, surgery, systemic diseases, and inflammations) were defined and correlated with 798 separate diagnoses. From 11 diagnoses/events ascribed to the clinical cases, 11,198 namings resulted. Thus, a comparative study of complex etiologies and events leading to enucleation in different hospitals of a specific area may be performed using this electronic ophthalmopathologic data bank system. The complexity of rare disease and integration into a superimposed structure can be managed with this custom-made data bank. A chronologically and demographically oriented consideration of reasons for enucleation is thus feasible.

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.

Partial central diabetes insipidus in patient with common variable immunodeficiency.

PubMed

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

2012-07-03

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.

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.

Leptospirosis and Human Immunodeficiency Virus Co-Infection Among Febrile Inpatients in Northern Tanzania

PubMed Central

Biggs, Holly M.; Galloway, Renee L.; Bui, Duy M.; Morrissey, Annie B.; Maro, Venance P.

2013-01-01

Abstract Background Leptospirosis and human immunodeficiency virus (HIV) infection are prevalent in many areas, including northern Tanzania, yet little is known about their interaction. Methods We enrolled febrile inpatients at two hospitals in Moshi, Tanzania, over 1 year and performed HIV antibody testing and the microscopic agglutination test (MAT) for leptospirosis. Confirmed leptospirosis was defined as ≥four-fold rise in MAT titer between acute and convalescent serum samples, and probable leptospirosis was defined as any reciprocal MAT titer ≥800. Results Confirmed or probable leptospirosis was found in 70 (8.4%) of 831 participants with at least one serum sample tested. At total of 823 (99.0%) of 831 participants had HIV testing performed, and 203 (24.7%) were HIV infected. Among HIV-infected participants, 9 (4.4%) of 203 had confirmed or probable leptospirosis, whereas among HIV-uninfected participants 61 (9.8%) of 620 had leptospirosis. Leptospirosis was less prevalent among HIV-infected as compared to HIV-uninfected participants [odds ratio (OR) 0.43, p=0.019]. Among those with leptospirosis, HIV-infected patients more commonly presented with features of severe sepsis syndrome than HIV-uninfected patients, but differences were not statistically significant. Among HIV-infected patients, severe immunosuppression was not significantly different between those with and without leptospirosis (p=0.476). Among HIV-infected adolescents and adults, median CD4 percent and median CD4 count were higher among those with leptospirosis as compared to those with other etiologies of febrile illness, but differences in CD4 count did not reach statistical significance (p=0.015 and p=0.089, respectively). Conclusions Among febrile inpatients in northern Tanzania, leptospirosis was not more prevalent among HIV-infected patients. Although some indicators of leptospirosis severity were more common among HIV-infected patients, a statistically significant difference was not demonstrated. Among HIV-infected patients, those with leptospirosis were not more immunosuppressed relative to those with other etiologies of febrile illness. PMID:23663165

[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

School Phobia: A Critical Analysis of the Separation Anxiety Theory and an Alternative Conceptualization.

ERIC Educational Resources Information Center

Pilkington, Cynthia L.; Piersel, Wayne C.

1991-01-01

Reviews literature on school phobia which reveals predominant view concerning its etiology is separation anxiety theory. Critically analyzes theory on three grounds: methodological problems, lack of generalizability concerning pathological mother-child relationships, and lack of emphasis on external etiological variables. Recommends reexamining…

Immune Disorder HSCT Protocol

ClinicalTrials.gov

2017-11-17

Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

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.

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

Etiologic yield of subspecialists' evaluation of young children with global developmental delay.

PubMed

Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

2000-05-01

To determine the etiologic yield of subspecialists' evaluation of young children with global developmental delay. In addition, variables that may predict finding an underlying etiology were also identified. All children <5 years of age, referred over an 18-month period to subspecialty services for initial evaluation of a suspected developmental delay, were prospectively enrolled. Diagnostic yield was ascertained after the completion of clinical assessments and laboratory investigations requested by the evaluating physician. Ninety-nine children (71 boys) were found to have global developmental delay; 96% had a mild or moderate delay documented. An etiologic diagnosis was determined in 44. Four diagnoses (cerebral dysgenesis, hypoxic-ischemic encephalopathy, toxin exposure, chromosomal abnormalities) accounted for 34 of 44 (77%) of the diagnoses made. The presence of co-existing autistic traits was associated with significantly decreased diagnostic yield (0/19 vs 44/80, P <.0001), whereas specific historical features (eg, family history, toxin exposure, and perinatal difficulty; 23/32 vs 21/67, P =.0002) and findings on physical examination (eg, dysmorphology, microcephaly, and focal motor findings; 35/48 vs 9/51, P <.0001) were significantly associated with identifying a diagnosis. Multiple logistic regression analysis identified antenatal toxin exposure, microcephaly, focal motor findings, and the absence of autistic traits as significant predictor variables for the identification of an etiology. An etiologic diagnosis is often possible in the young child with global developmental delay, particularly in the absence of autistic features. Etiologic yield is augmented by presence of specific findings on history or physical examination on initial assessment.

Variance Component Selection With Applications to Microbiome Taxonomic Data.

PubMed

Zhai, Jing; Kim, Juhyun; Knox, Kenneth S; Twigg, Homer L; Zhou, Hua; Zhou, Jin J

2018-01-01

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.

Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines.

PubMed

Koff, Wayne C; Russell, Nina D; Walport, Mark; Feinberg, Mark B; Shiver, John W; Karim, Salim Abdool; Walker, Bruce D; McGlynn, Margaret G; Nweneka, Chidi Victor; Nabel, Gary J

2013-04-18

Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort

PubMed Central

Rajasingham, Radha; Rhein, Joshua; Klammer, Kate; Musubire, Abdu; Nabeta, Henry; Akampurira, Andrew; Mossel, Eric C.; Williams, Darlisha A.; Boxrud, Dave J.; Crabtree, Mary B.; Miller, Barry R.; Rolfes, Melissa A.; Tengsupakul, Supatida; Andama, Alfred O.; Meya, David B.; Boulware, David R.

2015-01-01

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical. PMID:25385864

Epidemiology of meningitis in an HIV-infected Ugandan cohort.

PubMed

Rajasingham, Radha; Rhein, Joshua; Klammer, Kate; Musubire, Abdu; Nabeta, Henry; Akampurira, Andrew; Mossel, Eric C; Williams, Darlisha A; Boxrud, Dave J; Crabtree, Mary B; Miller, Barry R; Rolfes, Melissa A; Tengsupakul, Supatida; Andama, Alfred O; Meya, David B; Boulware, David R

2015-02-01

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical. © The American Society of Tropical Medicine and Hygiene.

Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders

PubMed Central

Buchbinder, David; Baker, Rebecca; Lee, Yu Nee; Ravell, Juan; Zhang, Yu; McElwee, Joshua; Nugent, Diane; Coonrod, Emily M.; Durtschi, Jacob D.; Augustine, Nancy H.; Voelkerding, Karl V.; Csomos, Krisztian; Rosen, Lindsey; Browne, Sarah; Walter, Jolan E.; Notarangelo, Luigi D.; Hill, Harry R.; Kumánovics, Attila

2015-01-01

Purpose Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients. Methods Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients. Results Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection. Conclusion Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments. PMID:25516070

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

An Increased Risk of Osteoporosis during Acquired Immunodeficiency Syndrome.

PubMed

Annapoorna, N; Rao, G Venkateswara; Reddy, N S; Rambabu, P; Rao, K R S Samabasiva

2004-01-01

Osteoporosis is characterized by decreased bone mineral density and mechanistic imbalances of bone tissue that may result in reduced skeletal strength and an enhanced susceptibility to fractures. Osteoporosis in its most common form affects the elderly (both sexes) and all racial groups of human beings. Multiple environmental risk factors like acquired immune deficiency syndrome (AIDS) are believed to be one of the causes of osteoporosis. Recently a high incidence of osteoporosis has been observed in human immunodeficiency virus (HIV) infected individuals. The etiology of this occurrence in HIV infections is controversial. This problem seems to be more frequent in patients receiving potent antiretroviral therapy. In AIDS, the main suggested risk factors for the development of osteoporosis are use of protease inhibitors, longer duration of HIV infection, lower body weight before antiretroviral therapy, high viral load. Variations in serum parameters like osteocalcin, c-telopeptide, levels of elements like Calcium, Magnesium, Phosphorus, concentration of vitamin-D metabolites, lactate levels, bicarbonate concentrations, amount of alkaline phosphatase are demonstrated in the course of development of osteoporosis. OPG/RANKL/RANK system is final mediator of bone remodeling. Bone mineral density (BMD) test is of added value to assess the risk of osteoporosis in patients infected with AIDS. The biochemical markers also aid in this assessment. Clinical management mostly follows the lines of treatment of osteoporosis and osteopenia.

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

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.

Intra- and extra-capsular hip fractures in the elderly: Two different pathologies?

PubMed

Dinamarca-Montecinos, J L; Prados-Olleta, N; Rubio-Herrera, R; Castellón-Sánchez del Pino, A; Carrasco-Buvinic, A

2015-01-01

To compare intracapsular (IC) and extracapsular (EC) hip fractures (HIF) in elderly patients in order to determine if they are different pathologies. Longitudinal, observational, descriptive, analytical prospective design, using a non-probabilistic sample from a full sample collection with 647 subjects (male and female), of 60 or more years old, admitted with HIF to the Department of Orthopedics and Traumatology of the Hospital, between January 1, 2010 and December 31, 2012. Follow-up was for 1 year post HIF. Socio-demographic, etiological, developmental, therapeutic and prognostic variables are compared. This is the first study on this subject with Latin American population. EC HIF incidence was superior to IC, contrary to that published in European/American populations. There are significant differences in etiological variables (χ(2)=6.34, p<0.042), with traumatic etiology in EC and non-traumatic in IC. There are also differences in therapeutic interventions performed (osteosynthesis for EC, arthroplasty for IC), with the decision on not to operate being lower in IC (both p<0.0000). The variables associated with the decision on not to perform surgery are age, etiology and postoperative mortality. The results are similar to other studies, adding the IC association with non-traumatic origin, in particular the trend of statistical association between IC and non-primary osteoporotic pathology (neoplasms, renal osteodystrophy, primary hyperparathyroidism). A further analysis was performed on the differences between Latin American and European/American populations in the incidence of either type of HIF. There are important etiological and therapeutic differences between IC and EC HIF; therefore it would be advisable to consider them as distinct disease entities. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

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

Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme

PubMed Central

Dhalla, F; da Silva, S P; Lucas, M; Travis, S; Chapel, H

2011-01-01

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immunodeficiencies in adults. They comprise a heterogeneous group of pathologies, with frequent non-infectious complications in addition to the bacterial infections that usually characterize their presentation. Complications include a high risk of malignancy, especially lymphoma and gastric cancer. Helicobacter pylori infection and pernicious anaemia are risk predictors for gastric cancer in the general population and probably in patients with CVIDs. Screening for gastric cancer in a high-risk population appears to improve survival. Given the increased risk of gastric cancer in patients with CVIDs and prompted by a case of advanced gastric malignancy in a patient with a CVID and concomitant pernicious anaemia, we performed a review of the literature for gastric cancer and conducted a cohort study of gastric pathology in 116 patients with CVIDs under long-term follow-up in Oxford. Regardless of the presence of pernicious anaemia or H. pylori infection, patients with CVIDs have a 10-fold increased risk of gastric cancer and are therefore a high-risk population. Although endoscopic screening of all patients with CVIDs could be considered, a more selective approach is appropriate and we propose a surveillance protocol that should reduce modifiable risk factors such as H. pylori, in order to improve the management of patients with CVIDs at risk of gastric malignancy. PMID:21470209

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.

Etiologic profile of spastic quadriplegia in children.

PubMed

Venkateswaran, Sunita; Shevell, Michael I

2007-09-01

The etiologic profile and possible predictors of etiology in children with spastic quadriplegia were assessed in a consecutive cohort of children with this motor impairment. Medical records from a single pediatric neurology practice over a 14-year interval were retrospectively and systematically reviewed. Variables comprised possible demographic, prenatal, perinatal, and postnatal risk factors. Of the 99 patients included in the study, 39 were premature (<37 weeks gestation). The overall etiologic yield was 83%. The top three diagnoses were hypoxic-ischemic perinatal asphyxia (33%), periventricular leukomalacia (15%), and central nervous system infections (11%). In premature children, the most common diagnoses were periventricular leukomalacia (33%), perinatal asphyxia (26%), and central nervous system infections (15%). In term-born children, the most frequent diagnoses were perinatal asphyxia (37%), metabolic disease (12%), and structural malformation or infection (9% each). Factors predicting the identification of an etiology included male sex (P = 0.05), low birth weight (P = 0.003), prematurity (P = 0.01), perinatal complications (P = 0.002), and neonatal encephalopathy (P = 0.006). The etiologic yield in patients with spastic quadriplegia was 83%, with differing underlying etiologies depending on gestational age. These results should help guide physicians in investigating possible underlying etiologies in patients with spastic quadriplegia.

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

Management of children with prolonged diarrhea

PubMed Central

Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

2016-01-01

Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded. PMID:26962439

Management of children with prolonged diarrhea.

PubMed

Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

2016-01-01

Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded.

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.

A Case Report of a Child with Bell's Palsy.

PubMed

Ramphul, Kamleshun; Mejias, Stephanie G; Ramphul-Sicharam, Yogeshwaree; Hamid, Ezatullah; Sonaye, Ruhi

2018-04-02

Bell's palsy is a neuropathy involving the seventh cranial nerve, also known as the facial nerve. It is usually caused by traumatic, infective, inflammatory or compressive conditions on the nerve. Many cases are also with no identifiable etiologies and are classified as idiopathic. Acute inflammation and edema of the cranial nerve seven can lead to the compression and eventual ischemia. The most common viral cause of Bell's palsy is herpes simplex virus but there are several reports of other viruses such as Epstein-Barr virus, human immunodeficiency virus and the hepatitis B virus involved in with similar presentation. Presentation of Bell's palsy in the pediatric population is quite rare and this makes early recognition and proper treatment important. We present a case of a three-year-old male with Bell's palsy.

SALMONELLA SEPTIC BURSITIS OF THE ANKLE IN A HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENT: A CASE REPORT AND LITERATURE REVIEW.

PubMed

Hiransuthikul, Akarin; Hiransuthikul, Narin

2016-11-01

Salmonella is an unusual cause of septic bursitis of the ankle. A 48-yearold male fish-merchant with a history of HIV infection with a CD4 cell count of 79 cells/ml presented with pain of the left ankle for 2 weeks and fever for 1 day. The bursal fluid was aspirated and culture of the fluid revealed Salmonella group D. He was treated initially with intravenous ceftriaxone 2g once daily for 5 days, followed by oral ciprofloxacin 500mg twice daily for 4 weeks to give a treatment course of 5 weeks. Follow-up visit revealed complete recovery without any residual defects. Salmonella should be considered in the differential of the etiology of immunosuppressed patient with septic bursitis.

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

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.

An etiologic classification of autism spectrum disorders.

PubMed

Gabis, Lidia V; Pomeroy, John

2014-05-01

Autism spectrum disorders (ASD) represent a common phenotype related to multiple etiologies, such as genetic, brain injury (e.g., prematurity), environmental (e.g., viral, toxic), multiple or unknown causes. To devise a clinical classification of children diagnosed with ASD according to etiologic workup. Children diagnosed with ASD (n = 436) from two databases were divided into groups of symptomatic cryptogenic or idiopathic, and variables within each database and diagnostic category were compared. By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. Differences in gender and clinical and diagnostic features were found when etiology was used to create subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s).

[Epidemiologic findings of the etiology of psychogenic diseases].

PubMed

Franz, M; Schellberg, D; Schepank, H

1993-01-01

In an epidemiological longitudinal field study, a sample of high risk probands suffering from medium psychogenic impairment was investigated with regard to the etiological relevancy of factors influencing psychogenic disorders (psychoneuroses, character neuroses, psychosomatic and/or psychosomatic functional diseases). The study focused the question of the etiological impact of personality, life events, and social support. With theoretical reference to the psychodynamic concept of personality trained physicians and psychologists investigated 240 probands in a half standardized psychodynamic interview which included psychometric and social empiric instruments. Expert ratings and self ratings were used to assess the current psychogenic impairment. The impact of the constructs personality, critical life events, and social support on psychogenic impairment was specified in two path models. In both models psychodynamic personality variables had the highest impact on the criterium. Psychodynamically consistent, the ability to establish mature object relations and the maturity of ego functions was inversely related to the degree of psychogenic impairment, whereas an immature organisation of defense mechanisms exerted an aggravating influence on the severity of impairment. The present path analyses altogether point to a possible central etiological impact of personality and/or psychodynamic variables on the severity of psychogenic impairment.

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

Clinical and Molecular Aspects of an Informative Family with Neurofibromatosis Type 1 and Noonan Phenotype

PubMed Central

Stevenson, David A.; Viskochil, David H.; Rope, Alan F.; Carey, John C.

2011-01-01

NF-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndromes, which are separate syndromes. Potential etiologies of NF-Noonan syndrome include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS. PMID:16542390

On the etiology of tropical spastic paraparesis and human T-cell lymphotropic virus-I-associated myelopathy.

PubMed

Zaninovic, V

1999-01-01

The purpose of this review is to present some concepts on the etiology of tropical spastic paraparesis or human T-cell lymphotropic virus-I (HTLV-I)-associated myelopathy (TSP/HAM). The large number of syndromes that have been associated with HTLV-I (60 to date), the existence of TSP/HAM cases associated with other retroviruses (human immunodeficiency virus-2 [HIV-2], HTLV-II), the existence of many TSPs without HTLV-I, and the evidence of clear epidemiologic contradictions in TSP/HAM indicate that the etiopathogenesis of TSP/HAM is not yet clear. Tropical spastic paraparesis/HAM affects patients of all human ethnic groups, but usually in well localized and relatively isolated geographic regions where HTLV-I has been endemic for a long time. Environmental factors and geographic locations appear to be critical factors. Because the neuropathology of TSP/HAM suggests a toxometabolic, rather than a viral cause, it is proposed that an intoxication similar to neurolathyrism could account for some of TSP/HAM cases, mainly in tropical and subtropical countries. If this were the case, HTLV-I could be a cofactor or act as a bystander. it is possible that co-infection with another agent is necessary to produce TSP/HAM and most of the syndromes associated with HTLV-I.

A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS) is aggravated in APOBEC3 deficient mice

PubMed Central

2012-01-01

Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs). Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus. PMID:22691411

An Increased Risk of Osteoporosis during Acquired Immunodeficiency Syndrome

PubMed Central

2004-01-01

Osteoporosis is characterized by decreased bone mineral density and mechanistic imbalances of bone tissue that may result in reduced skeletal strength and an enhanced susceptibility to fractures. Osteoporosis in its most common form affects the elderly (both sexes) and all racial groups of human beings. Multiple environmental risk factors like acquired immune deficiency syndrome (AIDS) are believed to be one of the causes of osteoporosis. Recently a high incidence of osteoporosis has been observed in human immunodeficiency virus (HIV) infected individuals. The etiology of this occurrence in HIV infections is controversial. This problem seems to be more frequent in patients receiving potent antiretroviral therapy. In AIDS, the main suggested risk factors for the development of osteoporosis are use of protease inhibitors, longer duration of HIV infection, lower body weight before antiretroviral therapy, high viral load. Variations in serum parameters like osteocalcin, c-telopeptide, levels of elements like Calcium, Magnesium, Phosphorus, concentration of vitamin-D metabolites, lactate levels, bicarbonate concentrations, amount of alkaline phosphatase are demonstrated in the course of development of osteoporosis. OPG/RANKL/RANK system is final mediator of bone remodeling. Bone mineral density (BMD) test is of added value to assess the risk of osteoporosis in patients infected with AIDS. The biochemical markers also aid in this assessment. Clinical management mostly follows the lines of treatment of osteoporosis and osteopenia. PMID:15912194

Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.

PubMed Central

Harakeh, S; Jariwalla, R J; Pauling, L

1990-01-01

We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions. Images PMID:1698293

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.

Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency.

PubMed

Azizi, G; Kiaee, F; Hedayat, E; Yazdani, R; Dolatshahi, E; Alinia, T; Sharifi, L; Mohammadi, H; Kavosi, H; Jadidi-Niaragh, F; Ziaee, V; Abolhassani, H; Aghamohammadi, A

2018-05-01

Common variable immunodeficiency (CVID) is the most prevalent symptomatic type of human primary immunodeficiency diseases (PID). Clinically, CVID is characterized by increased susceptibility to infections and a wide variety of autoimmune and rheumatologic disorders. All patients with CVID registered in Iranian PID Registry (IPIDR) were enrolled in this retrospective cohort study. We investigated the frequency of rheumatologic diseases and its association with immunological and clinical phenotypes in patients with CVID. A total of 227 patients with CVID were enrolled in this study. The prevalence of rheumatologic disorders was 10.1% with a higher frequency in women than men. Most common rheumatologic manifestations were juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) followed by juvenile spondyloarthritis (JSpA) and undifferentiated inflammatory arthritis (UIA). Septic arthritis in patients with CVID with a history of RA and JIA was higher than patients without rheumatologic complication. Patients with CVID with a history of autoimmunity (both rheumatologic and non-rheumatologic autoimmunity) had lower regulatory T cells counts in comparison with patients without autoimmune disorders. There was an association between defect in specific antibody responses and negative serologic test results in patients with rheumatologic manifestations. JIA, RA, JSpA and UIA are the most frequent rheumatologic disorders in patients with CVID. Due to antibody deficiency, serologic tests may be negative in these patients. Therefore, these conditions pose significant diagnostic and therapeutic challenges for immunologists and rheumatologists in charge of the care for these patients. © 2018 The Foundation for the Scandinavian Journal of Immunology.

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.

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.

Epidemiology of infectious meningitis in the State of Amazonas, Brazil.

PubMed

Saraiva, Maria das Graças Gomes; Santos, Eyde Cristianne Saraiva; Saraceni, Valéria; Rocha, Lívia Laura dos Santos; Monte, Rossicléia Lins; Albuquerque, Bernardino Cláudio de; Bastos, Michele de Souza; Santos, Marcelo Cordeiro dos; Monteiro, Wuelton Marcelo; Mourão, Maria Paula Gomes; Guerra, Marcus Vinitius de Farias; Lacerda, Marcus Vinícius Guimarães de

2015-01-01

In the State of Amazonas, particularly in the capital Manaus, meningitis has affected populations of different cultures and social strata over the years. Bacterial meningitis is caused by several different species and represents a major issue of public health importance. The present study reports the meningitis case numbers with different etiologies in Amazonas from January 1976 to December 2012. Since the 1970s, the (currently named) Tropical Medicine Foundation of Doutor Heitor Vieira Dourado [Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD)] has remained a reference center in Amazonas for the treatment of meningitis through the diagnosis and notification of cases and the confirmation of such cases using specific laboratory tests. The foundation has achieved coverage of over 90% of the state medical records for many years. Between 1990 and 2012, meningitis cases caused by Haemophilus influenzae decreased with the introduction of the H. influenzae vaccine. Meningococcal disease previously had a higher frequency of serogroup B disease, but starting in 2008, the detection of serogroup C increased gradually and has outpaced the detection of serogroup B. Recently, surveillance has improved the etiological definition of viral meningitis at FMT-HVD, with enteroviruses, Epstein-Barr virus (EBV) and varicella zoster virus (VZV) prevailing in this group of pathogens. With the advent of acquired immunodeficiency syndrome (AIDS), cryptococcal meningitis has become an important disease in Amazonas. Additionally, infectious meningitis is an important burden in the State of Amazonas. Changes in the epidemiological profile for the different etiology-defined cases are the result of continuous epidemiological surveillance and laboratory capacity improvements and control measures, such as Haemophilus influenzae vaccination.

Etiology of AIDS: biological and biochemical characteristics of HTLV-III.

PubMed

Markham, P D; Shaw, G M; Salahuddin, S Z; Hahn, B; Sarngadharan, M G; Gallo, R C

1985-01-01

The newly identified human HTLV-III virus, the etiologic agent for AIDS, shares many of the biological and physicochemical properties common to a family of retroviruses named human T-cell leukemia (lymphotropic) viruses, or HTLV. Because of the similarities, and because of the uniform nomenclature for human T-cell leukemia (lymphotropic) viruses adopted at the first Cold Spring Harbor Meeting on HTLV (19, 79), this newly discovered virus associated with AIDS as HTLV-III was named HTLV-III. Other investigators making independent isolations of virus have suggested naming the virus lymphadenopathy virus or LAV (3, 16), immunodeficiency associated virus or IADV (48), AIDS-related virus (41). Immunological and nucleic acid comparison has now demonstrated that these viruses are, not surprisingly, very similar to HTLV-III (55, 63, 78). In view of the wide range of disease manifestations caused by the virus, and previous discussions concerning a uniform nomenclature for human T-lymphotropic retroviruses, it would seem ill-advised to restrict the name of this virus to one clinical manifestation of one disease. The frequent isolation of HTLV-III from patients with AIDS and ARC, the detection of antibodies specific for HTLV-III in nearly all patients with these diseases and in a high proportion of individuals at risk, and finally its effect on cells in vitro, leaves little doubt that HTLV-III is causatively involved in the development of these diseases. This etiologic association is further strengthened by the detection of HTLV-III infection in many instances where a direct cause-and-effect association can be made, e.g., hemophiliacs and children with AIDS, and blood from HTLV-III infected donors and the otherwise normal recipients of this blood who subsequently develop AIDS.

Mathematical Ability of 10-Year-Old Boys and Girls: Genetic and Environmental Etiology of Typical and Low Performance

ERIC Educational Resources Information Center

Kovas, Yulia; Haworth, Claire M. A.; Petrill, Stephen A.; Plomin, Robert

2007-01-01

The genetic and environmental etiologies of 3 aspects of low mathematical performance (math disability) and the full range of variability (math ability) were compared for boys and girls in a sample of 5,348 children age 10 years (members of 2,674 pairs of same-sex and opposite-sex twins) from the United Kingdom (UK). The measures, which we…

A framework for measurement and harmonization of pediatric multiple sclerosis etiologic research studies: The Pediatric MS Tool-Kit.

PubMed

Magalhaes, Sandra; Banwell, Brenda; Bar-Or, Amit; Fortier, Isabel; Hanwell, Heather E; Lim, Ming; Matt, Georg E; Neuteboom, Rinze F; O'Riordan, David L; Schneider, Paul K; Pugliatti, Maura; Shatenstein, Bryna; Tansey, Catherine M; Wassmer, Evangeline; Wolfson, Christina

2018-06-01

While studying the etiology of multiple sclerosis (MS) in children has several methodological advantages over studying etiology in adults, studies are limited by small sample sizes. Using a rigorous methodological process, we developed the Pediatric MS Tool-Kit, a measurement framework that includes a minimal set of core variables to assess etiological risk factors. We solicited input from the International Pediatric MS Study Group to select three risk factors: environmental tobacco smoke (ETS) exposure, sun exposure, and vitamin D intake. To develop the Tool-Kit, we used a Delphi study involving a working group of epidemiologists, neurologists, and content experts from North America and Europe. The Tool-Kit includes six core variables to measure ETS, six to measure sun exposure, and six to measure vitamin D intake. The Tool-Kit can be accessed online ( www.maelstrom-research.org/mica/network/tool-kit ). The goals of the Tool-Kit are to enhance exposure measurement in newly designed pediatric MS studies and comparability of results across studies, and in the longer term to facilitate harmonization of studies, a methodological approach that can be used to circumvent issues of small sample sizes. We believe the Tool-Kit will prove to be a valuable resource to guide pediatric MS researchers in developing study-specific questionnaire.

Sclerosing Cholangitis: Clinicopathologic Features, Imaging Spectrum, and Systemic Approach to Differential Diagnosis.

PubMed

Seo, Nieun; Kim, So Yeon; Lee, Seung Soo; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Moon-Gyu

2016-01-01

Sclerosing cholangitis is a spectrum of chronic progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts, which can be classified as primary and secondary sclerosing cholangitis. Primary sclerosing cholangitis is a chronic progressive liver disease of unknown cause. On the other hand, secondary sclerosing cholangitis has identifiable causes that include immunoglobulin G4-related sclerosing disease, recurrent pyogenic cholangitis, ischemic cholangitis, acquired immunodeficiency syndrome-related cholangitis, and eosinophilic cholangitis. In this review, we suggest a systemic approach to the differential diagnosis of sclerosing cholangitis based on the clinical and laboratory findings, as well as the typical imaging features on computed tomography and magnetic resonance (MR) imaging with MR cholangiography. Familiarity with various etiologies of sclerosing cholangitis and awareness of their typical clinical and imaging findings are essential for an accurate diagnosis and appropriate management.

Reproduction of Epstein-Barr Virus Infection and Pathogenesis in Humanized Mice

PubMed Central

2014-01-01

Epstein-Barr virus (EBV) is etiologically associated with a variety of diseases including lymphoproliferative diseases, lymphomas, carcinomas, and autoimmune diseases. Humans are the only natural host of EBV and limited species of new-world monkeys can be infected with the virus in experimental conditions. Small animal models of EBV infection, required for evaluation of novel therapies and vaccines for EBV-associated diseases, have not been available. Recently the development of severely immunodeficient mouse strains enabled production of humanized mice in which human immune system components are reconstituted and express their normal functions. Humanized mice can serve as infection models for human-specific viruses such as EBV that target cells of the immune system. This review summarizes recent studies by the author's group addressing reproduction of EBV infection and pathogenesis in humanized mice. PMID:24605074

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.

A de novo whole gene deletion of XIAP detected by exome sequencing analysis in very early onset inflammatory bowel disease: a case report.

PubMed

Kelsen, Judith R; Dawany, Noor; Martinez, Alejandro; Martinez, Alejuandro; Grochowski, Christopher M; Maurer, Kelly; Rappaport, Eric; Piccoli, David A; Baldassano, Robert N; Mamula, Petar; Sullivan, Kathleen E; Devoto, Marcella

2015-11-18

Children with very early-onset inflammatory bowel disease (VEO-IBD), those diagnosed at less than 5 years of age, are a unique population. A subset of these patients present with a distinct phenotype and more severe disease than older children and adults. Host genetics is thought to play a more prominent role in this young population, and monogenic defects in genes related to primary immunodeficiencies are responsible for the disease in a small subset of patients with VEO-IBD. We report a child who presented at 3 weeks of life with very early-onset inflammatory bowel disease (VEO-IBD). He had a complicated disease course and remained unresponsive to medical and surgical therapy. The refractory nature of his disease, together with his young age of presentation, prompted utilization of whole exome sequencing (WES) to detect an underlying monogenic primary immunodeficiency and potentially target therapy to the identified defect. Copy number variation analysis (CNV) was performed using the eXome-Hidden Markov Model. Whole exome sequencing revealed 1,380 nonsense and missense variants in the patient. Plausible candidate variants were not detected following analysis of filtered variants, therefore, we performed CNV analysis of the WES data, which led us to identify a de novo whole gene deletion in XIAP. This is the first reported whole gene deletion in XIAP, the causal gene responsible for XLP2 (X-linked lymphoproliferative Disease 2). XLP2 is a syndrome resulting in VEO-IBD and can increase susceptibility to hemophagocytic lymphohistocytosis (HLH). This identification allowed the patient to be referred for bone marrow transplantation, potentially curative for his disease and critical to prevent the catastrophic sequela of HLH. This illustrates the unique etiology of VEO-IBD, and the subsequent effects on therapeutic options. This cohort requires careful and thorough evaluation for monogenic defects and primary immunodeficiencies.

Validation of Demographics, Etiology, and Risk Factors for Chronic Pancreatitis in the USA: A Report of the North American Pancreas Study (NAPS) Group.

PubMed

Conwell, Darwin L; Banks, Peter A; Sandhu, Bimaljit S; Sherman, Stuart; Al-Kaade, Samer; Gardner, Timothy B; Anderson, Michelle A; Wilcox, C Mel; Lewis, Michele D; Muniraj, Thiruvengadam; Forsmark, Christopher E; Cote, Gregory A; Guda, Nalini M; Tian, Ye; Romagnuolo, Joseph; Wisniewski, Stephen R; Brand, Randall; Gelrud, Andres; Slivka, Adam; Whitcomb, David C; Yadav, Dhiraj

2017-08-01

Our aim was to validate recent epidemiologic trends and describe the distribution of TIGAR-O risk factors in chronic pancreatitis (CP) patients. The NAPS-2 Continuation and Validation (NAPS2-CV) study prospectively enrolled 521 CP patients from 13 US centers from 2008 to 2012. CP was defined by definitive changes in imaging, endoscopy, or histology. Data were analyzed after stratification by demographic factors, physician-defined etiology, participating center, and TIGAR-O risk factors. Demographics and physician-defined etiology in the NAPS2-CV study were similar to the original NAPS2 study. Mean age was 53 years (IQR 43, 62) with 55% males and 87% white. Overall, alcohol was the single most common etiology (46%) followed by idiopathic etiology (24%). Alcohol etiology was significantly more common in males, middle-aged (35-65 years), and non-whites. Females and elderly (≥65 years) were more likely to have idiopathic etiology, while younger patients (<35 years) to have genetic etiology. Variability in etiology was noted by participating centers (e.g., alcohol etiology ranged from 27 to 67% among centers enrolling ≥25 patients). Smoking was the most commonly identified (59%) risk factor followed by alcohol (53%), idiopathic (30%), obstructive (19%), and hyperlipidemia (13%). The presence of multiple TIGAR-O risk factors was common, with 1, 2, ≥3 risk factors observed in 27.6, 47.6, and 23.6% of the cohort, respectively. Our data validate the current epidemiologic trends in CP. Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor. Identification of multiple risk factors suggests CP to be a complex disease.

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

Etiology of homosexuality and attitudes toward same-sex parenting: a randomized study.

PubMed

Frias-Navarro, Dolores; Monterde-I-Bort, Hector; Pascual-Soler, Marcos; Badenes-Ribera, Laura

2015-01-01

Attribution theory suggests the hypothesis that heterosexuals' attitudes toward homosexual sexual orientation will be more negative when homosexuality is attributed to controllable causes. Our randomized study analyzed (a) whether beliefs about the genetic or environmental etiology of the homosexual sexual orientation can be immediately modified by reading a text and (b) the causal effect of attributions about the controllability (environmental etiology) or noncontrollability (genetic etiology) of homosexual sexual orientation on the rejection of same-sex parenting and their social rights. The sample was composed of 190 Spanish university students with a mean age of 22.07 years (SD = 8.46). The results show that beliefs about the etiology of the sexual orientation could be modified by means of a written text. Furthermore, participants who believed that sexual orientation had a genetic etiology showed greater support for social rights and less rejection of same-sex parenting. However, the effects were detected only when there was a traditional opposition to the family with same-sex parenting. When the opposition was normative, the effect was not statistically significant. Our results can be useful in planning variables for intervention programs designed to foster tolerance toward and normality of sexual diversity.

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.

The role of Epstein-Barr virus in systemic lupus erythematosus.

PubMed

McClain, M T; Harley, J B; James, J A

2001-10-01

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechanisms behind these clinical findings and the etiologic events preceding and causing disease onset, however, remain largely unknown. For many years, investigators have suspected that Epstein-Barr virus might somehow be involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies have examined this possibility from various angles and have arrived at different conclusions. This work reviews these historical papers in the context of new results and presents a hypothetical role for this virus as an etiological environmental trigger for SLE.

Status epilepticus in pregnancy: Etiology, management, and clinical outcomes.

PubMed

Rajiv, Keni Ravish; Radhakrishnan, Ashalatha

2017-11-01

Status epilepticus (SE) in pregnancy carries significant risk to both mother and fetus. There is limited literature available on SE occurring in pregnancy world-over, with majority being from obstetric centers. All women who developed SE related to pregnancy (gestation, labor, or puerperium) between January 2000 and December 2016 were included in the study. Data were collected from our SE registry, maintained, and archived in the institute. The variables influencing the maternal and fetal outcome were compared using Student's t-test for continuous variables and Fisher's exact test for discrete variables. During the 16-year study period, a total of 348 SE events were recorded in 294 patients. Among these, there were 138 women, of which 17 had SE related to pregnancy. The etiology of SE was remote symptomatic in two and acute symptomatic in 15 patients. The various causes detected after initial evaluation for acute symptomatic SE were eclampsia (n=4), posterior reversible encephalopathy syndrome due to various causes other than eclampsia (n=6), cortical venous thrombosis (n=3), subarachnoid hemorrhage (n=1), and NMDA receptor antibody-mediated encephalitis (n=1).13 of 17 women with SE (76%) had good outcome. Majority of the fetuses had good outcomes, i.e., Category 1 (n=9, 57%). Duration of intensive care unit stay (p=0.029) and Status Epilepticus Severity Score (p=0.0324) at admission, were found to be significantly associated with poor outcomes. In any patient presenting with SE occurring in pregnancy, though eclampsia is presumed to be the most common overall cause; it is relevant to consider other etiologies such as posterior reversible encephalopathy syndrome, cortical venous thrombosis, and autoimmune encephalitis especially in cases presenting with refractory SE. Posterior reversible encephalopathy may occur in pregnancy due to diverse etiologies other than eclampsia. Copyright © 2017 Elsevier Inc. All rights reserved.

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

The etiology, risk factors, and interactions of enteric infections and malnutrition and the consequences for child health and development study (MAL-ED): description of the Tanzanian site.

PubMed

Mduma, Estomih R; Gratz, Jean; Patil, Crystal; Matson, Kristine; Dakay, Mary; Liu, Sarah; Pascal, John; McQuillin, Lauren; Mighay, Emmanuel; Hinken, Elizabeth; Ernst, Alexandra; Amour, Caroline; Mvungi, Regisiana; Bayyo, Eliwaza; Zakaria, Yeconia; Kivuyo, Sokoine; Houpt, Eric R; Svensen, Erling

2014-11-01

The Haydom, Tanzania, site (TZH) of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) Study is in north-central Tanzania, 300 km from the nearest urban center. TZH is in a remote rural district where most of the population are agropastoralists and grow maize as the staple food. The average household size is 7. The average woman achieves a parity of 6 and has 1 child death. Socioeconomic indicators are poor, with essentially no household having access to electricity, piped water, or improved sanitary facilities (compared with 14%, 7%, and 12%, respectively, reported nationally). The Demographic Health Survey Tanzania 2004 indicated that the region had high rates of stunting and underweight (40% and 31% of children aged <5 years had a height-for-age z score and weight-for-age z score, respectively, of <-2 ) and an under-5 child mortality rate of 5.8%. Human immunodeficiency virus prevalence among 18-month-old children is <0.5%. TZH represents a remote rural African population with profound poverty and malnutrition, but a strong community-based research infrastructure. © 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.

Epidemiologic overview of malignant lymphoma

PubMed Central

2012-01-01

Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend. PMID:22783355

Polymerase chain reaction-based detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid for the diagnosis of pneumocystis pneumonia.

PubMed

Oren, Ilana; Hardak, Emilia; Finkelstein, Renato; Yigla, Mordechai; Sprecher, Hannah

2011-09-01

The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes. During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms. In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold. Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS.

PubMed

Limou, Sophie; Coulonges, Cédric; Herbeck, Joshua T; van Manen, Daniëlle; An, Ping; Le Clerc, Sigrid; Delaneau, Olivier; Diop, Gora; Taing, Lieng; Montes, Matthieu; van't Wout, Angélique B; Gottlieb, Geoffrey S; Therwath, Amu; Rouzioux, Christine; Delfraissy, Jean-François; Lelièvre, Jean-Daniel; Lévy, Yves; Hercberg, Serge; Dina, Christian; Phair, John; Donfield, Sharyne; Goedert, James J; Buchbinder, Susan; Estaquier, Jérôme; Schächter, François; Gut, Ivo; Froguel, Philippe; Mullins, James I; Schuitemaker, Hanneke; Winkler, Cheryl; Zagury, Jean-François

2010-09-15

The compilation of previous genomewide association studies of AIDS shows a major polymorphism in the HCP5 gene associated with both control of the viral load and long-term nonprogression (LTNP) to AIDS. To look for genetic variants that affect LTNP without necessary control of the viral load, we reanalyzed the genomewide data of the unique LTNP Genomics of Resistance to Immunodeficiency Virus (GRIV) cohort by excluding "elite controller" patients, who were controlling the viral load at very low levels (<100 copies/mL). The rs2234358 polymorphism in the CXCR6 gene was the strongest signal (P=2.5 x 10(-7); odds ratio, 1.85) obtained for the genomewide association study comparing the 186 GRIV LTNPs who were not elite controllers with 697 uninfected control subjects. This association was replicated in 3 additional independent European studies, reaching genomewide significance of P(combined)=9.7 x 10(-10). This association with LTNP is independent of the CCR2-CCR5 locus and the HCP5 polymorphisms. The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in LTNP, emphasizing the power of extreme-phenotype cohorts. CXCR6 is a chemokine receptor that is known as a minor coreceptor in human immunodeficiency virus type 1 infection but could participate in disease progression through its role as a mediator of inflammation.

A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models

PubMed Central

Raulji, Payal; Mohapatra, Subhra; Mohapatra, Shyam S

2015-01-01

Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections. PMID:26407080

Persistent Pneumonia in an Infant.

PubMed

Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn; Van Opstal, Elizabeth

2015-07-01

A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made. Copyright © 2015 by the American Academy of Pediatrics.

Combination of Arsenic and Interferon-α Inhibits Expression of KSHV Latent Transcripts and Synergistically Improves Survival of Mice with Primary Effusion Lymphomas

PubMed Central

El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

2013-01-01

Background Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Methodology/Principal Findings Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. Conclusion/Significance These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients. PMID:24250827

Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

PubMed

El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

2013-01-01

Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

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.

Negative role of malnutrition in cell-mediated immune response: Pneumocystis jirovecii pneumonia (PCP) in a severely malnourished, HIV-negative patient with anorexia nervosa.

PubMed

Hanachi, Mouna; Bohem, Vanessa; Bemer, Pauline; Kayser, Nadja; de Truchis, Pierre; Melchior, Jean-Claude

2018-06-01

It is generally acknowledged that malnutrition is a propensity factor for secondary infections in different clinical situations (malnutrition-associated infections in hospitalized patients and malnourished children in developing countries). However, it is not clear how malnutrition might facilitate the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients without a definite etiology (disease or treatment) of impaired cell-mediated immune response. We report here on a case of Pneumocystis jirovecii pneumonia in an HIV-negative patient suffering from anorexia nervosa with extreme malnutrition, which had a favorable outcome despite the severity of her respiratory failure. This report indicates the need for the early screening of nutritional status and rapid treatment initiation in patients with malnutrition, as well as the determination of opportunistic infections in the event of a low lymphocyte count. Copyright © 2018. Published by Elsevier Ltd.

HIV and Ischemic Heart Disease.

PubMed

Vachiat, Ahmed; McCutcheon, Keir; Tsabedze, Nqoba; Zachariah, Don; Manga, Pravin

2017-01-03

The association of coronary heart disease (CHD) and human immunodeficiency virus (HIV) infection has been well recognized for many years. The etiology of the increased prevalence of CHD in HIV-infected populations is the result of complex interactions among the viral infection, host factors, traditional risk factors, and therapies for HIV. As the HIV population is living longer, largely attributable to combination antiretroviral therapy, there is concern about the effect of the rising prevalence of CHD on morbidity and mortality, as well its effect on health systems around the world. This review will highlight the epidemiological evidence linking HIV infection and CHD. It will also focus on our current understanding of the pathogenesis and factors associated with HIV infection and CHD. In addition, the review will highlight modes of presentation and management strategies for mitigating risk and treatment of HIV-positive patients presenting with CHD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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.

Dominant inheritance of cerebral gigantism.

PubMed

Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

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

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

Species interactions may help explain the erratic periodicity of whooping cough dynamics.

PubMed

Bhattacharyya, Samit; Ferrari, Matthew J; Bjørnstad, Ottar N

2017-12-14

Incidence of whooping cough exhibits variable dynamics across time and space. The periodicity of this disease varies from annual to five years in different geographic regions in both developing and developed countries. Many hypotheses have been put forward to explain this variability such as nonlinearity and seasonality, stochasticity, variable recruitment of susceptible individuals via birth, immunization, and immune boosting. We propose an alternative hypothesis to describe the variability in periodicity - the intricate dynamical variability of whooping cough may arise from interactions between its dominant etiological agents of Bordetella pertussis and Bordetella parapertussis. We develop a two-species age-structured model, where two pathogens are allowed to interact by age-dependent convalescence of individuals with severe illness from infections. With moderate strength of interactions, the model exhibits multi-annual coexisting attractors that depend on the R 0 of the two pathogens. We also examine how perturbation from case importation and noise in transmission may push the system from one dynamical regime to another. The coexistence of multi-annual cycles and the behavior of switching between attractors suggest that variable dynamics of whopping cough could be an emergent property of its multi-agent etiology. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A new model of wheezing severity in young children using the validated ISAAC wheezing module: A latent variable approach with validation in independent cohorts.

PubMed

Brunwasser, Steven M; Gebretsadik, Tebeb; Gold, Diane R; Turi, Kedir N; Stone, Cosby A; Datta, Soma; Gern, James E; Hartert, Tina V

2018-01-01

The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0-2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders. We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma.

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.

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.

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.

Observers' Agreement on Measurements in Fiberoptic Endoscopic Evaluation of Swallowing.

PubMed

Pilz, Walmari; Vanbelle, Sophie; Kremer, Bernd; van Hooren, Michel R; van Becelaere, Tine; Roodenburg, Nel; Baijens, Laura W J

2016-04-01

This study analyzed the effect that dysphagia etiology, different observers, and bolus consistency might have on the level of agreement for measurements in FEES images reached by independent versus consensus panel rating. Sixty patients were included and divided into two groups according to dysphagia etiology: neurological or head and neck oncological. All patients underwent standardized FEES examination using thin and thick liquid consistencies. Two observers scored the same exams, first independently and then in a consensus panel. Four ordinal FEES variables were analyzed. Statistical analysis was performed using a linear weighted kappa coefficient and Bayesian multilevel model. Intra- and interobserver agreement on FEES measurements ranged from 0.76 to 0.93 and from 0.61 to 0.88, respectively. Dysphagia etiology did not influence observers' agreement level. However, bolus consistency resulted in decreased interobserver agreement for all measured FEES variables during thin liquid swallows. When rating on the consensus panel, the observers deviated considerably from the scores they had previously given on the independent rating task. Observer agreement on measurements in FEES exams was influenced by bolus consistency, not by dysphagia etiology. Therefore, observer agreement on FEES measurements should be analyzed by taking bolus consistency into account, as it might affect the interpretation of the outcome. Identifying factors that might influence agreement levels could lead to better understanding of the rating process and assist in developing a more precise measurement scale that would ensure higher levels of observer agreement for measurements in FEES exams.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

Combined pituitary hormone deficiency: current and future status.

PubMed

Castinetti, F; Reynaud, R; Quentien, M-H; Jullien, N; Marquant, E; Rochette, C; Herman, J-P; Saveanu, A; Barlier, A; Enjalbert, A; Brue, T

2015-01-01

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

Etiological Theories of Adolescent Idiopathic Scoliosis: Past and Present

PubMed Central

Fadzan, Maja; Bettany-Saltikov, Josette

2017-01-01

Adolescent idiopathic scoliosis is one of the most common spinal deformities, yet its cause is unknown. Various theories look to biomechanical, neuromuscular, genetic, and environmental origins, yet our understanding of scoliosis etiology is still limited. Determining the cause of a disease is crucial to developing the most effective treatment. Associations made with scoliosis do not necessarily point to causality, and it is difficult to determine whether said associations are primary (playing a role in development) or secondary (develop as a result of scoliosis). Scoliosis is a complex condition with highly variable expression, even among family members, and likely has many causes. These causes could be similar among homogenous groups of AIS patients, or they could be individual. Here, we review the most prevalent theories of scoliosis etiology and recent trends in research. PMID:29399224

Genomic organization, sequence divergence, and recombination of feline immunodeficiency virus from lions in the wild

PubMed Central

Pecon-Slattery, Jill; McCracken, Carrie L; Troyer, Jennifer L; VandeWoude, Sue; Roelke, Melody; Sondgeroth, Kerry; Winterbach, Christiaan; Winterbach, Hanlie; O'Brien, Stephen J

2008-01-01

Background Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion. Results In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions. Genome organization of FIVPle subtype B (9891 bp) from lions in the Serengeti National Park in Tanzania and FIVPle subtype E (9899 bp) isolated from lions in the Okavango Delta in Botswana, both resemble FIV genome sequence from puma, Pallas cat and domestic cat across 5' LTR, gag, pol, vif, orfA, env, rev and 3'LTR regions. Comparative analyses of available full-length FIV consisting of subtypes A, B and C from FIVFca, Pallas cat FIVOma and two puma FIVPco subtypes A and B recapitulate the species-specific monophyly of FIV marked by high levels of genetic diversity both within and between species. Across all FIVPle gene regions except env, lion subtypes B and E are monophyletic, and marginally more similar to Pallas cat FIVOma than to other FIV. Sequence analyses indicate the SU and TM regions of env vary substantially between subtypes, with FIVPle subtype E more related to domestic cat FIVFca than to FIVPle subtype B and FIVOma likely reflecting recombination between strains in the wild. Conclusion This study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity. These full-length lion lentiviruses are integral to the advancement of comparative genomics of human pathogens, as well as emerging disease in wild populations of endangered species. PMID:18251995

Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS

PubMed Central

Limou, Sophie; Coulonges, Cédric; Herbeck, Joshua T.; van Manen, Daniëlle; An, Ping; Le Clerc, Sigrid; Delaneau, Olivier; Diop, Gora; Taing, Lieng; Montes, Matthieu; van't Wout, Angélique B.; Gottlieb, Geoffrey S.; Therwath, Amu; Rouzioux, Christine; Delfraissy, Jean-François; Lelièvre, Jean-Daniel; Lévy, Yves; Hercberg, Serge; Dina, Christian; Phair, John; Donfield, Sharyne; Goedert, James J.; Buchbinder, Susan; Estaquier, Jérôme; Schächter, François; Gut, Ivo; Froguel, Philippe; Mullins, James I.; Schuitemaker, Hanneke; Winkler, Cheryl; Zagury, Jean-François

2010-01-01

Background. The compilation of previous genomewide association studies of AIDS shows a major polymorphism in the HCP5 gene associated with both control of the viral load and long-term nonprogression (LTNP) to AIDS. Methods. To look for genetic variants that affect LTNP without necessary control of the viral load, we reanalyzed the genomewide data of the unique LTNP Genomics of Resistance to Immunodeficiency Virus (GRIV) cohort by excluding “elite controller” patients, who were controlling the viral load at very low levels (<100 copies/mL). Results. The rs2234358 polymorphism in the CXCR6 gene was the strongest signal (P = 2.5 × 10−7; odds ratio, 1.85) obtained for the genomewide association study comparing the 186 GRIV LTNPs who were not elite controllers with 697 uninfected control subjects. This association was replicated in 3 additional independent European studies, reaching genomewide significance of Pcombined = 9.7 × 10−10. This association with LTNP is independent of the combined CCR2-CCR5 locus and the HCP5 polymorphisms. Conclusion. The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in LTNP, emphasizing the power of extreme-phenotype cohorts. CXCR6 is a chemokine receptor that is known as a minor coreceptor in human immunodeficiency virus type 1 infection but could participate in disease progression through its role as a mediator of inflammation. PMID:20704485

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

PubMed Central

Lin, Kuan-Yin; Chen, Guan-Jhou; Lee, Yu-Lin; Huang, Yi-Chia; Cheng, Aristine; Sun, Hsin-Yun; Chang, Sui-Yuan; Liu, Chun-Eng; Hung, Chien-Ching

2017-01-01

Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies. PMID:28611512

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review.

PubMed

Lin, Kuan-Yin; Chen, Guan-Jhou; Lee, Yu-Lin; Huang, Yi-Chia; Cheng, Aristine; Sun, Hsin-Yun; Chang, Sui-Yuan; Liu, Chun-Eng; Hung, Chien-Ching

2017-05-28

Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

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.…

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.

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.

The validity of tooth grinding measures: etiology of pain dysfunction syndrome revisited.

PubMed

Marbach, J J; Raphael, K G; Dohrenwend, B P; Lennon, M C

1990-03-01

The current study explores the proposition that a treating clinician's etiologic model influences patients' reports of tooth grinding, the validity of, and subsequent research findings relying on these measures. The investigation compares self-reports of tooth grinding and related clinical variables for 151 cases of temporomandibular pain and dysfunction syndrome (TMPDS) treated by a clinician who does not explicitly support the grinding theory of the etiology of TMPDS, and 139 healthy controls. Cases were no more likely than well controls to report ever-grinding, but were actually significantly less likely than well controls to report current grinding. They were also significantly more likely to report that a dentist had told them they ground. Findings suggest that studies using self-report, clinician-report of tooth grinding (or both) are methodologically inadequate for addressing the relationship between tooth grinding and TMPDS.

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.

Predisposition Factors in Anorexia Nervosa.

ERIC Educational Resources Information Center

Nagel, K. L.; Jones, Karen H.

1992-01-01

Reviews literature concerned with investigating psychiatric disturbances and genetic variables hypothesized as predisposing factors in etiology of anorexia nervosa. Gives particular emphasis to research which discusses association between anorexia nervosa and depression. Reviews psychopharmacological evidence and family genetics studies. Offers…

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

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.

Vulnerability of women living with HIV/aids1

PubMed Central

Duarte, Marli Teresinha Cassamassimo; Parada, Cristina Maria Garcia de Lima; de Souza, Lenice do Rosário

2014-01-01

Objective outline the profile of women living with the human immunodeficiency virus/aids in interior cities in São Paulo State, in the attempt to identify characteristics related to individual, social and programmatic vulnerability and to analyze the conditions in which they discovered their serological status. Method between October 2008 and December 2010, a cross-sectional study was undertaken with 184 women attended at a specialized service. The data were collected through an interview and gynecological test, including the collection of samples for the etiological diagnosis of sexually transmissible conditions. Results the women were predominantly white, between 30 and 49 years of age, lived with a partner, had a low education level, multiple sexual partners across the lifetime and unsafe sexual practices. The prevalence of sexually transmitted diseases corresponded to 87.0%. Conclusion the study suggests the need to offer gynecological care in specialized services and the accomplishment of multiprofessional actions to reinforce the female autonomy in protective decision making. PMID:24553705

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.

The Interaction Between Human Papillomavirus and Other Viruses

PubMed Central

Guidry, J. T.; Scott, R. S.

2016-01-01

The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV) JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas. PMID:27826043

Use of ATP analogs to inhibit HIV-1 transcription

PubMed Central

Narayanan, Aarthi; Sampey, Gavin; Van Duyne, Rachel; Guendel, Irene; Kehn-Hall, Kylene; Roman, Jessica; Currer, Robert; Galons, Hervé; Oumata, Nassima; Joseph, Benoît; Meijer, Laurent; Caputi, Massimo; Nekhai, Sergei; Kashanchi, Fatah

2012-01-01

Human immunodeficiency virus type 1 (HIV-1) is the etiological agent of AIDS. Chronic persistent infection is an important reason for the presence of “latent cell populations” even after Anti Retroviral Therapy (ART). We have analyzed the effect of ATP analogs in inhibiting cdk9/T1 complex in infected cells. A third generation drug named CR8#13 is an effective inhibitor of Tat activated transcription. Following drug treatment, we observed a decreased loading of cdk9 onto the HIV-1 DNA. We found multiple novel cdk9/T1 complexes present in infected and uninfected cells with one complex being unique to infected cells. This complex is sensitive to CR8#13 in kinase assays. Treatment of PBMC with CR8#13 does not kill infected cells as compared to Flavopiridol. Interestingly, there is a difference in sensitivity of various clades to these analogs. Collectively, these results point to targeting novel complexes for inhibition of cellular proteins that are unique to infected cells. PMID:22771113

Usher syndrome with psychotic symptoms: two cases in the same family.

PubMed

Wu, Chen-Ying; Chiu, Chih-Chiang

2006-10-01

Usher syndrome is a heterogeneous autosomal recessive disorder characterized by hearing and visual sensory impairment. Retinitis pigmentosa is essential for its diagnosis. There are only a few reports describing patients with Usher syndrome presenting with psychotic features and the etiology of its psychiatric manifestation is still unknown. Herein, the authors report variable congenital hearing impairment and progressive visual loss occurring in five of seven family members and two of them meeting the diagnostic criteria of Usher syndrome with psychotic features. Furthermore, the authors compare their psychiatric symptoms with other reports and the possible etiologies of psychotic symptoms are discussed.

[Pseudomigraine with pleocytosis].

PubMed

Pariso, Gabriela S; Parisi, Virginia L; Persi, Gabriel G; Canto, Lucila; Rugilo, Carlos A; Gatto, Emilia M

2006-01-01

The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis or pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis (HaNDL) is a syndrome consisting of recurrent headaches, reversible neurological deficit, lymphocytic pleocytosis in cerebrospinal fluid (CSF), variable duration over time and spontaneous resolution. Although several etiopathogenic mechanisms have been suggested (vascular, infectous, immunological and calcium channelopthy), its etiology remains unknown. We describe a 28 year old female, with recurrent migraine with pleocytosis, confusional syndrome and transient neurological deficit. The clinical remission was achieved within two months. Although its etiology remains unknown the differential diagnosis is discussed in order to keep in mind this syndrome.

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

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.

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.

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.

[Traditional Chinese medicine syndrome factors of patients with HIV infection or AIDS in China].

PubMed

Jiang, Feng; Fu, Lin-chun; Ma, Jian-ping; Zhou, Qing; Peng, Bo; Xie, Shi-ping; Guo, Hui-jun; Dong, Yong-xin; Ma, Xiu-lan; Guo, Xuan-xian; Xie, Zhong-li; Hu, Yan-ping; Li, Qing-ya; Li, Hua-wei; Jin, Yan-tao

2011-09-01

To study the characteristics of traditional Chinese medicine (TCM) syndrome factors of patients from different areas of China with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). A cross-sectional investigation study was conducted in Henan, Guangdong and Yunnan Provinces and Xinjiang Uygur Autonomous Region of China from October 2008 to August 2010. Based on literature review and expert opinion, a clinical questionnaire of TCM syndromes was drawn up. This survey was carried out after the investigators were professionally trained. Wenfeng III Auxiliary Diagnosis and Treat System of TCM was used to analyze the frequencies of AIDS patients' signs and symptoms with scores above 70 of syndrome factors respectively. Based on this work, syndrome factors of AIDS were analyzed in different areas. There were 608 HIV/AIDS cases investigated from October 2008 to August 2010 in total; among them, 276 cases were from Henan, 126 cases from Guangdong, 120 cases from Xinjiang and 86 cases from Yunnan. The results of syndrome factor analysis indicated that the syndromes of four provinces were similar. HIV/AIDS patients in the four areas exhibited qi deficiency, blood deficiency, yin deficiency, yang deficiency, dampness, phlegm, qi stagnation and essence deficiency syndromes. Patients in each area also had their own characteristics, such as that the scores of dampness of Guangdong and yin deficiency of Xinjiang were higher than the other syndromes, whereas the scores of Henan Province were higher than the other areas. AIDS patients had higher scores of syndromes than HIV-infected patients. HIV/AIDS patients from different areas had similar syndrome elements. The theory of "AIDS toxin injuring primordial qi" can sum up the TCM etiology and pathogenesis of HIV/AIDS.

A Molecular Approach to Nested RT-PCR Using a New Set of Primers for the Detection of the Human Immunodeficiency Virus Protease Gene.

PubMed

Zarei, Mohammad; Ravanshad, Mehrdad; Bagban, Ashraf; Fallahi, Shahab

2016-07-01

The human immunodeficiency virus (HIV-1) is the etiologic agent of AIDS. The disease can be transmitted via blood in the window period prior to the development of antibodies to the disease. Thus, an appropriate method for the detection of HIV-1 during this window period is very important. This descriptive study proposes a sensitive, efficient, inexpensive, and easy method to detect HIV-1. In this study 25 serum samples of patients under treatment and also 10 positive and 10 negative control samples were studied. Twenty-five blood samples were obtained from HIV-1-infected individuals who were receiving treatment at the acquired immune deficiency syndrome (AIDS) research center of Imam Khomeini hospital in Tehran. The identification of HIV-1-positive samples was done by using reverse transcription to produce copy deoxyribonucleic acid (cDNA) and then optimizing the nested polymerase chain reaction (PCR) method. Two pairs of primers were then designed specifically for the protease gene fragment of the nested real time-PCR (RT-PCR) samples. Electrophoresis was used to examine the PCR products. The results were analyzed using statistical tests, including Fisher's exact test, and SPSS17 software. The 325 bp band of the protease gene was observed in all the positive control samples and in none of the negative control samples. The proposed method correctly identified HIV-1 in 23 of the 25 samples. These results suggest that, in comparison with viral cultures, antibody detection by enzyme linked immunosorbent assay (ELISAs), and conventional PCR methods, the proposed method has high sensitivity and specificity for the detection of HIV-1.

Epidemiology of non-keratinocytic skin cancers among persons with acquired immunodeficiency syndrome in the U.S.

PubMed Central

Lanoy, Emilie; Dores, Graça M.; Madeleine, Margaret M.; Toro, Jorge R.; Fraumeni, Joseph F.; Engels, Eric A.

2009-01-01

Objective Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with acquired immunodeficiency syndrome (AIDS). Design We linked data from population-based U.S. AIDS and cancer registries to evaluate risk of non-keratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497,142 persons with AIDS. Methods Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 count, and a geographic index of ultraviolet radiation exposure. Results From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR=1.3, 95%CI 1.1-1.4, n=292 cases) and, more strongly, of Merkel cell carcinoma (SIR=11, 95%CI 6.3-17, n=17) and sebaceous carcinoma (SIR=8.1, 95%CI 3.2-17, n=7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (p-trend=0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 count at AIDS onset (p=0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (p-trend<10-4 and p-trend=10-3, respectively). Conclusions Among persons with AIDS, there is a modest excess risk of melanoma which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression. PMID:19114864

Etiologies, clinical features and outcome of cardiac arrest in HIV-infected patients.

PubMed

Mongardon, Nicolas; Geri, Guillaume; Deye, Nicolas; Sonneville, Romain; Boissier, Florence; Perbet, Sébastien; Camous, Laurent; Lemiale, Virginie; Thirion, Marina; Mathonnet, Armelle; Argaud, Laurent; Bodson, Laurent; Gaudry, Stéphane; Kimmoun, Antoine; Legriel, Stéphane; Lerolle, Nicolas; Luis, David; Luyt, Charles-Edouard; Mayaux, Julien; Guidet, Bertrand; Pène, Frédéric; Mira, Jean-Paul; Cariou, Alain

2015-12-15

Compared to many other cardiovascular diseases, there is a paucity of data on the characteristics of successfully resuscitated cardiac arrest (CA) patients with human immunodeficiency virus (HIV) infection. We investigated causes, clinical features and outcome of these patients, and assessed the specific burden of HIV on outcome. Retrospective analysis of HIV-infected patients admitted to 20 French ICUs for successfully resuscitated CA (2000-2012). Characteristics and outcome of HIV-infected patients were compared to those of a large cohort of HIV-uninfected patients admitted after CA in the Cochin Hospital ICU during the same period. 99 patients were included (median CD4 lymphocyte count 233/mm(3), viral load 43 copies/ml). When compared with the control cohort of 1701 patients, HIV-infected patients were younger, with a predominance of male, a majority of in-hospital CA (52%), and non-shockable initial rhythm (80.8%). CA was mostly related to respiratory cause (n=36, including 23 pneumonia), cardiac cause (n=33, including 16 acute myocardial infarction), neurologic cause (n=8) and toxic cause (n=5). CA was deemed directly related to HIV infection in 18 cases. Seventy-one patients died in the ICU, mostly for care withdrawal after post-anoxic encephalopathy. After propensity score matching, ICU mortality was not significantly affected by HIV infection. Similarly, HIV disease characteristics had no impact on ICU outcome. Etiologies of CA in HIV-infected patients are miscellaneous and mostly not related to HIV infection. Outcome remains bleak but is similar to outcome of HIV-negative patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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...

Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant

ClinicalTrials.gov

2017-07-12

Adenosine Deaminase Deficiency; Autosomal Recessive Disorder; Immune System Disorder; Purine-Nucleoside Phosphorylase Deficiency; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency With Absence of T and B Cells; X-Linked Severe Combined Immunodeficiency

Alopecia Areata. Current situation and perspectives.

PubMed

Juárez-Rendón, Karina J; Rivera Sánchez, Gildardo; Reyes-López, Miguel Á; García-Ortiz, José E; Bocanegra-García, Virgilio; Guardiola-Avila, Iliana; Altamirano-García, María L

2017-12-01

Alopecia areata (AA) is a dermatological disease characterized by non-scarring hair loss of the scalp and/or body, with an unpredictable and variable evolution in the patients in which, despite multidisciplinary efforts, its etiology is not entirely known, although some evidence suggests that environmental, immunological and genetic factors could be generating the disease. The aim of this review is to provide an updated panorama of the clinical characteristics, diagnosis and treatment of AA, to analyze the mechanisms that could participate in its etiology, as well as to review some of the most important genetic variants that could confer susceptibility to the development of this disease. Sociedad Argentina de Pediatría.

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.

Ischemic stroke due to embolic heart diseases and associated factors in Benin hospital setting.

PubMed

Gnonlonfoun, Dieudonné; Adjien, Constant; Gnimavo, Ronald; Goudjinou, Gérard; Hotcho, Corine; Nyangui Mapaga, Jennifer; Sowanou, Arlos; Gnigone, Pupchen; Domingo, Rodrigue; Houinato, Dismand

2018-04-15

Poor access to cardiovascular checkups is a major cause of ignorance of embolic heart diseases as the etiology for ischemic stroke. Study ischemic strokes due to embolic heart diseases and their associated factors. It was a cross-sectional, prospective, descriptive and analytical study conducted from November 1, 2014 to August 31, 2015 on 104 patients with ischemic stroke confirmed through brain imaging. Embolic heart diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter, myocardial infarction (MI), heart valve diseases and atrial septal aneurysm (ASA). The dependent variable was embolic heart disease while independent variables encompassed socio-demographic factors, patients' history, and lifestyle. Data analysis was carried out through SAS 9.3. The rate of embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for heart valve diseases, MI and ASA. The associated factor was age (p=0.000). The diagnosis of a potential cardiac source of embolism is essential because of therapeutic and prognostic implications. Wherefore, there is need for cardiovascular examination particularly Holter ECG and cardiac ultrasound examination which are not always accessible to our populations. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

[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.

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...

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.

SCI Survey to Determine Pressure Ulcer Vulnerability in the Outpatient Population

DTIC Science & Technology

2013-10-01

of transportation, mobility, caregiver status, bowel and bladder continence, level of education , mental health status or illicit drug use. Key...coded a number of variables. For example, we created a new variable: “Good Nutrition ”, reflecting nutritional status using the recorded albumin and...no difference in age, level of education or marital status and presence of PrUs. Violence as the etiology of SCI was more common among those with ≥ 1

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

The Role of Infertility Etiology in Success Rate of Intrauterine Insemination Cycles: An Evaluation of Predictive Factors for Pregnancy Rate

PubMed Central

Ashrafi, Mahnaz; Rashidi, Mandana; Ghasemi, Afsaneh; Arabipoor, Arezoo; Daghighi, Sara; Pourasghari, Parisa; Zolfaghari, Zahra

2013-01-01

Background: The objective of this study was to identify the prognostic factors that influence the outcome of ovarian stimulation with intrauterine insemination (IUI) cycles in couples with different infertility etiology. Materials and Methods: This retrospective study was performed in data of 1348 IUI cycles with ovarian stimulation by clomiphene citrate (CC) and/or gonadotropins in 632 women with five different infertility etiology subgroups at Akbarabbadi Hospital, Tehran, Iran. Results: The pregnancy rate (PR)/ cycle was highest (19.9%) among couples with unexplained infertility and lowest (10.6%) in couples with multiple factors infertility. In cases of unexplained infertility, the best PRs were seen after CC plus gonadotropins stimulation (26.3%) and with inseminated motile sperm count>30×106 (21.9%), but the tendency didn’t reach statistical significant. In the ovarian factor group, the best PRs were observed in women aged between 30 and 34 years (20.8%), with 2-3 preovulatory follicles (37.8%) and infertility duration between 1and 3 years (20.8%), while only infertility duration (p=0.03) and number of preovulatory follicles (p=0.01) were statistically significant. Multiple logistic regression analysis determined that number of preovulatory follicles (p=0.02), duration of infertility (p=0.015), age (p=0.019), infertility etiology (p=0.05) and stimulation regimen (p=0.01) were significant independent factors in order to predict overall clinical PR. Conclusion: The etiology of infertility is important to achieve remarkable IUI success. It is worth mentioning that within different etiologies of infertility, the demographic and cycles characteristics of couples did not show the same effect. Favorable variables for treatment success are as follows: age <40, duration of infertility ≤5 years and a cause of infertility except of multiple factors. PMID:24520471

Cumulative trauma disorders: A review.

PubMed

Iqbal, Zaheen A; Alghadir, Ahmad H

2017-08-03

Cumulative trauma disorder (CTD) is a term for various injuries of the musculoskeletal and nervous systems that are caused by repetitive tasks, forceful exertions, vibrations, mechanical compression or sustained postures. Although there are many studies citing incidence of CTDs, there are fewer articles about its etiology, pathology and management. The aim of our study was to discuss the etiology, pathogenesis, prevention and management of CTDs. A literature search was performed using various electronic databases. The search was limited to articles in English language pertaining to randomized clinical trials, cohort studies and systematic reviews of CTDs. A total of 180 papers were identified to be relevant published since 1959. Out of these, 125 papers reported about its incidence and 50 about its conservative treatment. Workplace environment, same task repeatability and little variability, decreased time for rest, increase in expectations are major factors for developing CTDs. Prevention of its etiology and early diagnosis can be the best to decrease its incidence and severity. For effective management of CTDs, its treatment should be divided into Primordial, Primary, Secondary and Tertiary prevention.

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

Mathematical Ability of 10-Year-Old Boys and Girls: Genetic and Environmental Etiology of Typical and Low Performance

PubMed Central

Kovas, Yulia; Haworth, Claire M. A.; Petrill, Stephen A.; Plomin, Robert

2009-01-01

The genetic and environmental etiologies of 3 aspects of low mathematical performance (math disability) and the full range of variability (math ability) were compared for boys and girls in a sample of 5,348 children age 10 years (members of 2,674 pairs of same-sex and opposite-sex twins) from the United Kingdom (UK). The measures, which we developed for Web-based testing, included problems from 3 domains of mathematics taught as part of the UK National Curriculum. Using quantitative genetic model-fitting analyses, similar results were found for math disabilities and abilities for all 3 measures: Moderate genetic influence and environmental influence were mainly due to nonshared environmental factors that were unique to the individual, with little influence from shared environment. No sex differences were found in the etiologies of math abilities and disabilities. We conclude that low mathematical performance is the quantitative extreme of the same genetic and environmental factors responsible for variation throughout the distribution. PMID:18064980

Prevention of infection in children and adolescents with primary immunodeficiency disorders.

PubMed

Papadopoulou-Alataki, Efimia; Hassan, Amel; Davies, E Graham

2012-12-01

Primary Immunodeficiency diseases (PIDs) are a heterogenous group of inherited disorders that may involve one or multiple components of the immune system. PIDs are uncommon, chronic and severe disorders, in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. This review addresses the current practices for the prevention of infection in children and adolescents with PIDs, particular covering immunisations and antimicrobial prophylaxis. Over recent years, there have been major advances in molecular and cellular understanding in the field of PIDs. Many different disorders are recognised with variable spectra of infection susceptibility depending on the particular aspects of the immune response that are affected. Immunoglobulin prophylaxis is the mainstay of treatment for PIDs and provides passive protection. Prophylactic antimicrobials are efficacious in children and adolescents with predominant defects in primary T cell immunodeficiency diseases and phagocytic disorders, and also with predominant defects in antibody production. Prophylactic antibiotics are suggested for patients with antibody deficiency diseases if recurrent infections exceed three per year, if severe infections occur despite adequate immunoglobulin replacement and in hypogammaglobulinaemic patients who have bronchiectasis. Certain immunisations are effective in antibody deficiencies, T cell deficiencies, complement deficiencies and phagocytic disorders. There are remarkably few published data relating to clinical management aimed at preventing infectious complications in children and adolescents with PIDs. The cornerstones of the prevention of infection in most PID patients are: antimicrobial prophylaxis, appropriate vaccination, immunoglobulin replacement, for the more severe cases, and regular ongoing follow-up.

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

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study.

PubMed

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models. Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal. Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.

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.

The role of child sexual abuse in the etiology of substance-related disorders.

PubMed

Maniglio, Roberto

2011-01-01

To elucidate the role of child sexual abuse in the etiology of substance-related disorders, a systematic review of the several articles on the childhood sexual abuse-related risk for developing substance problems in adolescence or adulthood is provided. Seven databases were searched, supplemented with hand-search of reference lists. Six reviews, including 200 studies, were included. Results indicate that child sexual abuse is a statistically significant, although general and nonspecific, risk factor for substance problems. Other biological and psychosocial variables contribute to substance-related disorders, with sexual abuse conferring additional risk, either as a distal, indirect cause or as a proximal, direct cause. Recommendations for future research are provided.

Giant scrotal elephantiasis of inflammatory etiology: a case report

PubMed Central

Denzinger, Stefan; Watzlawek, Elke; Burger, Maximilian; Wieland, Wolf F; Otto, Wolfgang

2007-01-01

Background Scrotal lymphedema is rare outside endemic filariasis regions in Africa and Asia. It is of variable origin in the western world. Case presentation We present a case of a 40-year-old European man with massive elephantiasis of the scrotum attributed to chronic inflammation of the lower urinary tract caused by urinary outlet obstruction and diabetes mellitus. The patient underwent subtotal scrotectomy saving penis, testes and spermatic cords and followed by scrotal reconstruction with adequate cosmetic and functional outcome. Conclusion In this report we discuss a rare case of scrotal elephantiasis in an European patient, reflect on the etiology and the diagnostic and therapeutic approaches. Surgery can be successful even in giant scrotal elephantiasis. PMID:17543128

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.

Phenotypic characterization and genetic diversity of Flavobacterium columnare isolated from red tilapia, Oreochromis sp. in Thailand

USDA-ARS?s Scientific Manuscript database

Flavobacterium columnare is the etiologic agent of columnaris disease and severely affects various freshwater aquaculture fish species worldwide. The objectives of this study were to determine the phenotypic characteristics and genetic variability among F. columnare isolates isolated from red tilapi...

Some Aspects of Mental Retardation. A Training Guide for the Vocational Rehabilitation Counselor. Final Report.

ERIC Educational Resources Information Center

Phelps, William R.

Presented for vocational counselors is an overview of mental retardation, including the definition, and etiology. Described are the prenatal factors of heredity (including familial retardation and cranial anomalies), infections (including syphilis and encephalitis), radiation, blood group incompatibility, and unknown or variable etiological…

Psychological First Aid for Children Exposed to Sexual Violence.

ERIC Educational Resources Information Center

Fenlon, Michael J.; Mufson, Susan A.

1994-01-01

Researchers describe here the traumatic stress reactions of a group of fifth-grade children to the sexual assault of their classmate. The children's "secondary trauma"--trauma caused by empathizing or identifying with the victim--presented a distinct yet variable etiology. The authors offer suggestions for working with child secondary…

Sadness, Depression, and Avoidance Behavior

ERIC Educational Resources Information Center

Leventhal, Allan M.

2008-01-01

Research into genetic, psychosocial, and cognitive explanations for depression (biopsychosocial models) provides support for the role of these variables in the etiology of depression. Regularly identified as basic to depression is loss, and the experience of loss has been found to be more influential than genetic factors in the causation of…

A Self-Reinforcement Deficit in Depression: Fact or Artifact?

ERIC Educational Resources Information Center

Gotlib, Ian H.

The constructs of self-reinforcement and social skill have received increasing attention from researchers concerned with the etiology and maintenance of depression. These two variables, however, have not been empirically related. The relationship between depression, self-reinforcement, and social skill was examined with an interpersonal task.…

Toward an Etiology of Media Use Motivations: The Role of Temperament in Media Use.

ERIC Educational Resources Information Center

Sherry, John L.

2001-01-01

Shows that the biologically rooted individual difference behavior variable of temperament was consistent and moderately strong causal factor in forming television use motivations among undergraduate students. Finds distinct patterns of relationships between temperament and all television use gratifications supporting the uses and gratifications…

Implicit Attitudes toward Violence among Male Perpetrators of Intimate Partner Violence: A Preliminary Investigation

ERIC Educational Resources Information Center

Eckhardt, Christopher I.; Samper, Rita; Suhr, Laura; Holtzworth-Munroe, Amy

2012-01-01

Whereas cognitive variables are hypothesized to play an important role in intimate partner violence (IPV) etiology and intervention, cognitive assessment methods have largely targeted offenders' explicit, controlled cognitive processing using paper-and-pencil questionnaires prone to social desirability biases. Using an implicit measure of…

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.

Epstein-Barr virus and human diseases: recent advances in diagnosis.

PubMed Central

Okano, M; Thiele, G M; Davis, J R; Grierson, H L; Purtilo, D T

1988-01-01

Since the discovery of Epstein-Barr virus (EBV) from a cultured Burkitt's lymphoma cell line in 1964, the virus has been associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. During the recent decade, EBV has been etiologically implicated in a broad spectrum of human diseases. The precise role of this virus in these diseases is not well understood, but clearly, defective immunosurveillance against the virus may permit an uncontrolled proliferation of EBV-infected cells. As a result, a growing number of cases of EBV-associated B-cell proliferative diseases or lymphoma have been noted in patients with primary and acquired immunodeficiencies. These lymphoproliferative diseases and others, such as chronic mononucleosis syndrome, are leading to new areas of investigation which are providing information regarding the pathogenetic mechanisms of EBV-induced diseases. The early accurate diagnosis of EBV infection can be achieved by performing EBV-specific serology, detecting for EBV-determined nuclear antigen in tissues, establishing spontaneous lymphoid cell lines, and using molecular hybridization techniques for demonstrating the presence of viral genome in affected lesions. Images PMID:2848624

Fungal prostatitis: an update.

PubMed

Mayayo, Emilio; Fernández-Silva, Fabiola

2014-06-01

Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

[Digital ischemia revealing multiple myeloma].

PubMed

Khammar, Z; Ouazzani, M; Bennani, B; Oubelkacem, N; Berrady, R

2018-02-01

Digital ulcers generally arise in a context of microangiopathy-related focal ischemia. In women, connective tissue diseases are the main etiology, while in men the cause is often diffuse arterial disease, e.g. Leo-Buerger disease, or emboligenic heart disease. A paraneoplastic origin of digital necrosis due to ischemia is rarely reported. A 75-year-old man presented with cyanosis of the fingertips and toes that had begun one month earlier. The physical examination found pulp ulcers on the fingers and toes of both hands and feet. Two weeks later, necrotic damage developed distally, with no other associated symptoms. Blood tests were suggestive of Kahler disease; immunodeficiency disorders tests were negative; the cyroglobulin test was positive. Multiple-drug chemotherapy was followed by clinical improvement. Distal necrotic damage is a frequent inaugural symptom in vascular disease. If the common causal mechanisms (iatrogenic, occupational, toxic, atheromatous, emboligenic heart disease, or systemic disease) have been ruled out, it is important to search for a blood disorder or cancer as the cause of distal necrotic damage. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Understanding AIDS: historical interpretations and the limits of biomedical individualism.

PubMed Central

Fee, E; Krieger, N

1993-01-01

The popular and scientific understanding of acquired immunodeficiency syndrome (AIDS) in the United States has been shaped by successive historical constructions or paradigms of disease. In the first paradigm, AIDS was conceived of as a "gay plague," by analogy with the sudden, devastating epidemics of the past. In the second, AIDS was normalized as a chronic disease to be managed medically over the long term. By examining and extending critiques of both paradigms, it is possible to discern the emergence of an alternative paradigm of AIDS as a collective chronic infectious disease and persistent pandemic. Each of these constructions of AIDS incorporates distinct views of the etiology, prevention, pathology, and treatment of disease; each tacitly promotes different conceptions of the proper allocation of individual and social responsibility for AIDS. This paper focuses on individualistic vs collective, and biomedical vs social and historical, understandings of disease. It analyzes the use of individualism as methodology and as ideology, criticizes some basic assumptions of the biomedical model, and discusses alternative strategies for scientific research, health policy, and disease prevention. Images p1478-a p1480-a p1482-a PMID:8214245

Impact of xerostomia on oral health and quality of life among adults infected with HIV-1.

PubMed

Jeganathan, Sarangapany; Carey, Helen; Purnomo, Julianita

2012-01-01

The study investigated the impact of xerostomia on oral health and quality of life (QoL) among patients infected with human immunodeficiency virus (HIV) who were attending for routine HIV monitoring in Australia. This cross-sectional, self-administered questionnaire survey and oral screening (OS) included 100 subjects who were HIV positive. The OS was conducted by a dentist blinded to the subject's survey responses. Xerostomia was determined by asking the subjects a single question. Subjects with xerostomia were found to have increased caries activity and poorer QoL, especially in the psychological dimensions of the oral health impact profile. Age and duration of HIV infection were associated with xerostomia. Early diagnosis of xerostomia and intervention with preventive dental care would potentially reduce caries and improve QoL among patients infected with HIV-1. Ongoing chronic inflammation of salivary glands despite the beneficial effects of antiretroviral therapy may play a role in the etiology of xerostomia in patients infected with HIV and requires further study. © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Bacterial vaginosis: a public health problem for women.

PubMed

Rauh, V A; Culhane, J F; Hogan, V K

2000-01-01

Bacterial vaginosis (BV) remains a moderately prevalent condition with clearly observed links to adverse reproductive, gynecological, and other outcomes in women, including human immunodeficiency virus infection. Because of inconsistent findings from clinical studies concerning BV's etiologic role, no definitive policies with respect to screening and treatment have yet been established. Of concern is the high, unexplained prevalence of BV among African-American women, who are also at extremely high risk for preterm birth. The complexity of the sociodemographic picture challenges the field of public health to continue to explore the role of BV and its relationship to a whole host of social and biomedical conditions that may contribute to adverse health outcomes among society's most vulnerable members. Future decisions about screening and treatment, currently based on the biomedical model, may need to take into consideration issues of social context and expanded views of causality if we are to better understand and eliminate those factors that place individual women at risk of adverse outcomes, as well as the conditions that underlie racial and ethnic disparities in health.

Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus–Associated Pneumonia Among Children Aged <5 Years in the PERCH Study

PubMed Central

Le, Tham; O’Brien, Katherine L.; Murdoch, David R.; Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Scott, J. Anthony G.; Thea, Donald M.; Awori, Juliet O.; Baillie, Vicky L.; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Endtz, Hubert P.; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A.; Moore, David P.; Park, Daniel E.; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D.; Zeger, Scott L.; Deloria Knoll, Maria; Madhi, Shabir A.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Mahomed, Nasreen; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; Wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne

2017-01-01

Abstract Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. PMID:28575375

The epidemiology of classic, African, and immunosuppressed Kaposi's sarcoma.

PubMed

Wahman, A; Melnick, S L; Rhame, F S; Potter, J D

1991-01-01

The etiology of Kaposi's sarcoma remains somewhat obscure. While lesions of classic Kaposi's sarcoma, African Kaposi's sarcoma, and immunosuppressed Kaposi's sarcoma have been found to be indistinguishable from one another, the reasons for the variations in type and severity have not been established. The origin of the spindle cell is yet to be agreed on. Geographic variation does not seem as important as ethnic variation. The very young and the very old, perhaps two ages of weakened immunity, tend to have a higher incidence of Kaposi's sarcoma. Children and AIDS patients tend to develop more virulent disease. Males tend to get Kaposi's sarcoma at higher rates than do females. Jewish and Mediterranean males have the highest incidence of classic Kaposi's sarcoma, and African Bantu have the highest incidence of African Kaposi's sarcoma, classifications which do not apply to the Kaposi's sarcoma population in the United States. Male homosexuals have much higher incidence of Kaposi's sarcoma than do male heterosexuals, but since the early 1980s, its incidence as the presenting manifestation of AIDS has decreased dramatically. There is no unequivocal association with HLA haplotype (though DR5 carriers may be at especially high risk) or evidence of family clustering. There is an impressive but not always consistent association between Kaposi's sarcoma development and immunodeficiency. Environmental factors, such as nitrite use, immunosuppression, and repeated cytomegalovirus infection, are associated with Kaposi's sarcoma, but the exact mechanism is unclear and the associations remain inconsistent. Finally, it is still unclear if there is a causative infectious agent for Kaposi's sarcoma. While cytomegalovirus has been linked to Kaposi's sarcoma, there are weaknesses in its hypothetical role as an etiologic agent as is the case for HIV itself.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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.

[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.

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.

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 ...

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.

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

Personality Subtypes of Suicidal Adults

PubMed Central

Westen, Drew; Bradley, Rebekah

2009-01-01

Research into personality factors related to suicidality suggests substantial variability among suicide attempters. A potentially useful approach that accounts for this complexity is personality subtyping. As part of a large sample looking at personality pathology, this study used Q-factor analysis to identify subtypes of 311 adult suicide attempters using SWAP-II personality profiles. Identified subtypes included Internalizing, Emotionally Dysregulated, Dependent, Hostile-Isolated, Psychopathic, and Anxious-Somatizing. Subtypes differed in hypothesized ways on criterion variables that address their construct validity, including adaptive functioning, Axis I and II comorbidity, and etiology-related variables (e.g., history of abuse). Furthermore, dimensional ratings of the subtypes predicted adaptive functioning above DSM-based diagnoses and symptoms. PMID:19752649

Exploring the Etiology of Perfectionism and Perceptions of Self-Worth in Young Athletes

ERIC Educational Resources Information Center

McArdle, Siobhain; Duda, Joan L.

2008-01-01

This study assessed the main and interactive effects of perceived parental expectations and perceived parental criticism on 180 young talented athletes' perfectionistic tendencies and level and reported fluctuation in self-esteem. A potential quadratic effect of perceived parental expectations on the targeted dependent variables was also tested.…

Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure.

PubMed

Sinha, Amitasha; Patel, Yuval A; Cruise, Michael; Matsukuma, Karen; Zaheer, Atif; Afghani, Elham; Yadav, Dhiraj; Makary, Martin A; Hirose, Kenzo; Andersen, Dana K; Singh, Vikesh K

2016-04-01

Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p < 0.01). However, only a toxic etiology was an independent predictor of post-operative pain relief (OR 5.7, 95% CI 1.3, 24.5, p = 0.02). Only a toxic etiology, and not imaging or histopathologic findings, independently predicts post-operative pain relief in CP patients undergoing the Whipple or Frey procedure.

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation.

PubMed

McHugh, Kirk M

2014-04-01

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.

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.

[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.

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

Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

PubMed

Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

2014-08-20

Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating substantial to excellent interobserver reliability. This classification system will serve as a foundation to guide ongoing research efforts and standardize communication in the clinical setting. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

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.

Phenotype-genotype correlations in congenital isolated growth hormone deficiency (IGHD).

PubMed

Alatzoglou, Kyriaki S; Dattani, Mehul T

2012-01-01

Isolated growth hormone deficiency (IGHD) may be congenital, often due to genetic mutations, or acquired as a result of other factors such as cranial irradiation. The commonest genes implicated in its genetic etiology are those encoding growth hormone (GH1) and the receptor for GH-releasing hormone (GHRHR). Rarely, IGHD may be caused by mutations in transcription factors (HESX1, SOX3, OTX2) or be the first presentation before the development of other pituitary hormone deficiencies. IGHD has been classified in four genetic forms (type IA, IB, II and III). Despite the increasing number of genes implicated in the etiology of IGHD, mutations in known genes account only for a small percentage of cases; therefore, other as yet unidentified factors may be implicated in its etiology. Although there is no strict genotype/phenotype correlation in patients with IGHD, there are some emerging patterns that may guide us towards a genetic diagnosis of the condition. There is increasing understanding that the phenotype of patients with IGHD is highly variable and sometimes even evolving, dictating the need for long term follow-up in these cases.

Honoring the Past and Looking to the Future: Updates on Seminal Behavior Therapy Publications on Etiology and Mechanisms of Change.

PubMed

Newman, Michelle G

2016-09-01

This is the introduction to the first of two special issues in honor of the 50th anniversary of the Association for Behavioral and Cognitive Therapies. The goal of this issue is to pay tribute to prior seminal Behavior Therapy publications on etiology and mechanisms of change, to provide an updated review of important topics covered by these papers, and to make recommendations for the future. Each invited paper highlights a particular Behavior Therapy publication's contribution to our understanding and also provides an updated review or meta-analysis on the topic of the original paper. The topics covered here include mechanisms of etiology such as preparedness, reinforcement, and control. In terms of papers on mechanisms of change, we cover mechanisms related to extinction including fear activation, within- and between-session extinction, safety behaviors, and variables related to imagery. In addition, we examine principles related to generalization of learning and optimizing the impact of homework. With the two special issues of Behavior Therapy, we hope to inspire additional research and discussion. Copyright © 2016. Published by Elsevier Ltd.

Myodegeneration with fibrosis and regeneration in the pectoralis major muscle of broilers.

PubMed

Sihvo, H-K; Immonen, K; Puolanne, E

2014-05-01

A myopathy affecting the pectoralis major muscle of the commercial broiler has emerged creating remarkable economic losses as well as a potential welfare problem of the birds. We here describe the macroscopic and histologic lesions of this myopathy within 10 pectoralis major muscles of 5- to 6-week-old broilers in Finland. Following macroscopic evaluation and palpation of the muscles, a tissue sample of each was fixed in formalin, processed for histology, and histologically evaluated. The muscles that were macroscopically hard, outbulging, pale, and often accompanied with white striping histologically exhibited moderate to severe polyphasic myodegeneration with regeneration as well as a variable amount of interstitial connective tissue accumulation or fibrosis. All affected cases also exhibited perivenular lymphocyte accumulation. The etiology of this myodegenerative lesion remains yet open. Polyphasic myodegeneration is associated with several previously known etiologies, but palpatory hardness focusing on the pectoralis major, together with perivenular lymphocytes, has not been described in relation to them. The results of this study provide the pathological basis for further studies concerning the etiology of the currently described myopathy.

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.

Long-term outcome of visual internal urethrotomy for the management of pediatric urethral strictures.

PubMed

Hafez, Ashraf T; El-Assmy, Ahmed; Dawaba, Mohamed S; Sarhan, Osama; Bazeed, Mahmoud

2005-02-01

We evaluated the long-term results of visual internal urethrotomy for pediatric urethral strictures to evaluate the efficacy and final outcome of this procedure in children and to evaluate the risk factors for stricture recurrence. The computerized surgical records of our hospital were reviewed to identify children who underwent visual internal urethrotomy between 1980 and 2001. Hospital and followup clinical charts were then reviewed. Many variables were analyzed, including age, etiology, length and site of the strictures, and catheter duration. Only patients with a minimum followup of 2 years were included. Regular self-catheterization was not used by any child. A total of 31 patients (mean age 11.2 years, range 2 to 18) were identified. Followup ranged from 2 to 20 years, with a mean of 6.6 years. The most common etiology for stricture formation was failed previous urethroplasty and post instrumentation (35.5% and 32.3%, respectively). The success rate after initial urethrotomy was 35.5% (11 of 31 patients). Mean interval to first recurrence was 26 months. A second urethrotomy improved the success rate of 58.1%. Eight patients required 2 or more urethrotomies, of whom half required open urethroplasty. Among the evaluated variables only stricture length shorter than 1 cm was associated with good results. Visual internal urethrotomy provides a safe first line therapeutic option for pediatric urethral strictures shorter than 1 cm, independent of etiology and location. For patients with more than 1 recurrence or with strictures longer than 1 cm, who are at high risk for recurrence after internal urethrotomy, open urethroplasty remains the treatment of choice.

Investigation of Clinical Characteristics and Etiological Factors in Children with Molar Incisor Hypomineralization

PubMed Central

Giuca, Maria Rita; Cappè, Maria; Carli, Elisabetta; Lardani, Lisa

2018-01-01

Aim The purpose of the present study was to evaluate the clinical defects and etiological factors potentially involved in the onset of MIH in a pediatric sample. Methods 120 children, selected from the university dental clinic, were included: 60 children (25 boys and 35 girls; average age: 9.8 ± 1.8 years) with MIH formed the test group and 60 children (27 boys and 33 girls; average age: 10.1 ± 2 years) without MIH constituted the control group. Distribution and severity of MIH defects were evaluated, and a questionnaire was used to investigate the etiological variables; chi-square, univariate, and multivariate statistical tests were performed (significance level set at p < 0.05). Results A total of 186 molars and 98 incisors exhibited MIH defects: 55 molars and 75 incisors showed mild defects, 91 molars and 20 incisors had moderate lesions, and 40 molars and 3 incisors showed severe lesions. Univariate and multivariate statistical analysis showed a significant association (p < 0.05) between MIH and ear, nose, and throat (ENT) disorders and the antibiotics used during pregnancy (0.019). Conclusions Moderate defects were more frequent in the molars, while mild lesions were more frequent in the incisors. Antibiotics used during pregnancy and ENT may be directly involved in the etiology of MIH in children. PMID:29861729

Gorlin-Goltz Syndrome: Case report and literature review

PubMed Central

Ramesh, Maya; Krishnan, Ramesh; Chalakkal, Paul; Paul, George

2015-01-01

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, with complete penetrance and variable expressivity, though sporadic cases have been described. This article includes a case report and an extensive review of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumor and treatment modalities. PMID:26604511

Gorlin-Goltz Syndrome: Case report and literature review.

PubMed

Ramesh, Maya; Krishnan, Ramesh; Chalakkal, Paul; Paul, George

2015-01-01

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, with complete penetrance and variable expressivity, though sporadic cases have been described. This article includes a case report and an extensive review of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumor and treatment modalities.

Speech Deficits in Persons with Autism: Etiology and Symptom Presentation

ERIC Educational Resources Information Center

Matson, Johnny L.; Kozlowski, Alison M.; Matson, Michael M.

2012-01-01

Speech and other communication deficits are core features of the autism spectrum. This topic has become one of the most heavily studied in the child health/mental health field. Even within this group of disorders, considerable variability in symptoms is evident. A variety of subtopics within this area have been studied. Topics include types of…

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

The Etiology of Top-Tier Publications in Management: A Status Attainment Perspective on Academic Career Success

ERIC Educational Resources Information Center

Valle, Matthew; Schultz, Kaitlyn

2011-01-01

Purpose: The purpose of this paper is to develop and test a comprehensive model of personal and institutional input variables, composed of elements describing status-based antecedents, job/organizational context antecedents, and individual level antecedents, which may contribute to the production of significant (top-tier) research outputs in the…

HIV/AIDS-related attitudes and practices among traditional healers in Zambézia Province, Mozambique.

PubMed

Audet, Carolyn M; Blevins, Meridith; Moon, Troy D; Sidat, Mohsin; Shepherd, Bryan E; Pires, Paulo; Vergara, Alfredo; Vermund, Sten H

2012-12-01

To document HIV knowledge, treatment practices, and the willingness of traditional healers to engage with the health system in Zambézia Province, Mozambique. Traditional healers offer culturally acceptable services and are more numerous in Mozambique than are allopathic providers. Late presentation of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) is reported among persons who have first sought care from traditional healers. One hundred and thirty-nine (139) traditional healers were interviewed in their native languages (Chuabo or Lomwe) in Zambézia Province. Furthermore, 24 traditional healers were observed during patient encounters. Healers answered a semistructured questionnaire regarding their knowledge of HIV/AIDS, general treatment practices, attitudes toward the allopathic health system, and their beliefs in their abilities to cure AIDS. Traditional healers were older and had less formal education than the general population. Razor cutting in order to rub herbs into blooded skin was observed, and healers reported razor cutting as a routine practice. Healers stated that they did not refer HIV patients to clinics for two principal reasons: (1) patient symptoms/signs of HIV were unrecognized, and (2) practitioners believed they could treat the illness effectively themselves. Traditional healers were far more likely to believe in a spiritual than an infectious origin of HIV disease. Prior HIV/AIDS training was not associated with better knowledge or referral practices, though 81% of healers were interested in engaging allopathic providers. It was found that the HIV-related practices of traditional healers probably increase risk for both HIV-infected and uninfected persons through delayed care and reuse of razors. Mozambican traditional healers attribute HIV pathogenesis to spiritual, not infectious, etiologies. Healers who had received prior HIV training were no more knowledgeable, nor did they have better practices. The willingness expressed by 4 in 5 healers to engage local formal health providers in HIV/AIDS care suggests a productive way forward, though educational efforts must be effective and income concerns considered.

Etiological Beliefs, Treatments, Stigmatizing Attitudes toward Schizophrenia. What Do Italians and Israelis Think?

PubMed

Mannarini, Stefania; Boffo, Marilisa; Rossi, Alessandro; Balottin, Laura

2017-01-01

Background: Although scientific research on the etiology of mental disorders has improved the knowledge of biogenetic and psychosocial aspects related to the onset of mental illness, stigmatizing attitudes and behaviors are still very prevalent and pose a significant social problem. Aim: The aim of this study was to deepen the knowledge of how attitudes toward people with mental illness are affected by specific personal beliefs and characteristics, such as culture and religion of the perceiver. More precisely, the main purpose is the definition of a structure of variables, namely perceived dangerousness, social closeness, and avoidance of the ill person, together with the beliefs about the best treatment to be undertaken and the sick person' gender, capable of describing the complexity of the stigma construct in particular as far as schizophrenia is concerned. Method: The study involved 305 university students, 183 from the University of Padua, Italy, and 122 from the University of Haifa, Israel. For the analyses, a latent class analysis (LCA) approach was chosen to identify a latent categorical structure accounting for the covariance between the observed variables. Such a latent structure was expected to be moderated by cultural background (Italy versus Israel) and religious beliefs, whereas causal beliefs, recommended treatment, dangerousness, social closeness, and public avoidance were the manifest variables, namely the observed indicators of the latent variable. Results: Two sets of results were obtained. First, the relevance of the manifest variables as indicators of the hypothesized latent variable was highlighted. Second, a two-latent-class categorical dimension represented by prejudicial attitudes, causal beliefs, and treatments concerning schizophrenia was found. Specifically, the differential effects of the two cultures and the religious beliefs on the latent structure and their relations highlighted the relevance of the observed variables as indicators of the expected latent variable. Conclusion: The present study contributes to the improvement of the understanding of how attitudes toward people with mental illness are affected by specific personal beliefs and characteristics of the perceiver. The definition of a structure of variables capable of describing the complexity of the stigma construct in particular as far as schizophrenia is concerned was achieved from a cross-cultural perspective.

[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.

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.

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

Etiology, clinical profile and short-term outcome of acute kidney injury in children at a tertiary care pediatric nephrology center in Pakistan.

PubMed

Tresa, Vina; Yaseen, Afshan; Lanewala, Ali Asghar; Hashmi, Seema; Khatri, Sabeeta; Ali, Irshad; Mubarak, Muhammed

2017-11-01

The reported prevalence rates and etiologies of acute kidney injury (AKI) are quite variable in different regions of the world. The current study was planned to determine the etiology, clinical profile, and short-term outcome of pediatric AKI at our hospital. A prospective, observational study was carried out from April 2014 to March 2015. All pediatric patients (1 month to ≤15 years) diagnosed as AKI using modified pRIFLE criteria were studied and followed for 3 months to document short-term outcome. AKI was diagnosed in 116 children. The mean age was 7.5 ± 4.4 years and males were predominant (60.3%). At presentation, 83.6% had oliguria/anuria, 37.1% hypertension and 17.2% severe anemia. Etiology included primary renal (74/116; 63.8%), postrenal (28/116; 24.1%) and prerenal (11/116; 9.5%) causes. Postinfectious glomerulonephritis (PIGN) and crescentic glomerulonephritis in primary renal, obstructive urolithiasis in postrenal and sepsis in prerenal, were the most common etiologies. At presentation, 89/116 (76.7%) patients were in pRIFLE Failure category. Regarding outcome, 68 (58.6%) patients recovered, six (5.2%) died, 18 (15.5%) developed chronic kidney disease (CKD) and 22 (19%) end-stage renal disease (ESRD). Comparison of recovered and unrecovered AKI showed that characteristics such as hypertension, severe anemia, edema, volume overload, requirement of mechanical ventilation, initiation of dialysis and need of >5 sessions of dialysis had statistically significant (p <0.05) association with nonrecovery. Glomerulonephritides (PIGN and crescentic) and obstructive urolithiasis are major causes of pediatric AKI at our center. A fairly high percentage of cases recovered and these mainly comprised of PIGN and obstructive urolithiasis.

The etiology and determinants of hospital closure.

PubMed

Longo, D R; Sohn, M W; Shortell, S M

1996-01-01

This article examines the etiology of hospital closure and the correlates of hospital closure and the extent of similarity in this organizational outcome between pre- and post-Prospective Payment System (PPS) implementation. It also replicates a study from an earlier time period. Findings support the study's main hypotheses: in more stringent and turbulent markets, institutional and strategic variables are more important determinants of hospital closure. Merger acquisitions are found to be similar to both system acquisitions and autonomous hospitals. Standard Metropolitan Statistical Area (SMSA) status and regulation show an effect on hospital closure and merger acquisition. While many similarities exist when compared to the replicated study and findings prior to PPS implementation, it appears that sufficient differences exist to support the hypothesis that the PPS has an impact upon hospital organizational outcome.

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.

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

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.

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.

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

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

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.

"To Sleep, Perchance to Dream": The Role of Sleep Disturbance in the Multidimensional Treatment of a Male Bulimic.

ERIC Educational Resources Information Center

Rybicki, Daniel J.; Levitt, John

Eating disorders within males are relatively uncommon, with estimates suggesting incidence rates of only five percent of the sample. This single-subject, reversal design case study examines the etiological variables of a 22-year-old male bulimic patient. Consultation for treatment was made by the patient's parents. Family assessment made in the…

The Treatment of Anorexia Nervosa in a General Hospital: A Case Vignette of a Multi-Disciplinary General Hospital-Based Approach.

ERIC Educational Resources Information Center

Kronenberg, J.; And Others

1994-01-01

Describes anorexia nervosa as condition variable in etiology and resistant to treatment, which may lead to mortality in 5% of treated cases. Notes that efforts have been made for treating disorder in nonstigmatizing medical units outside psychiatric hospitals. Describes, through presentation of short case vignette, advantages of treating…

The Puerto Ricans: Culture Change and Language Deviance. Viking Fund Publications in Anthropology, Number 51.

ERIC Educational Resources Information Center

Leavitt, Ruby Rohrlich

This anthropological study examines whether sociocultural factors are basic to the etiology of stuttering through (1) an investigation of the incidence of stuttering in a single ethnic group, Puerto Rican rural migrants living in two different cultural milieus (San Juan and New York City), and (2) a comparison of the sociocultural variables in the…

Acute Liver Failure: Summary of a Workshop

PubMed Central

Lee, William M.; Squires, Robert H.; Nyberg, Scott L.; Doo, Edward; Hoofnagle, Jay H.

2011-01-01

Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (≈60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (≈25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research. PMID:18318440

Characteristics, correlates, and outcomes of childhood and adolescent depressive disorders

PubMed Central

Rao, Uma; Chen, Li-Ann

2009-01-01

Depressive illness beginning early in life can have serious developmental and functional consequences. Therefore, understanding the disorder during this developmental stage is critical for determining its etiology and course, as well as for deveiopinq effective intervention straieqies. This paper summarizes current knoviedqe reqardinq the etiology, phenomenoiogy, correlates, natural course, and consequences of unipolar depression in children and adolescents. Using adult depression as a framevork, the unique aspects of childhood and adolescence are considered in order to better understand depression within a developmental context. The data suggest that the clinical presentation, correlates, and natural course of depression are remarkably similar across the lifespan. There are, however, important developmental differences. Specifically, the familial and psychological context in which depression develops in youngsters is associated with variability in the frequency and nature of depressive symptoms and comorbid conditions among children and adolescents. Maturational differences have also been identified in the neurobiological correlates of depression. These developmental differences may be associated with the observed variability in clinical response to treatment and longitudinal course. Characterization of the developmental differences will be helpful in developing more specific and effective interventions for youngsters, thereby allowing them to reach their full potential as adults. PMID:19432387

Prevention, identification, and management of post-operative penile implant complications of infection, hematoma, and device malfunction

PubMed Central

O’Rourke, Timothy K.; Erbella, Alexander; Zhang, Yu

2017-01-01

Penile prosthesis implant surgery is an effective management approach for a number of urological conditions, including medication refractory erectile dysfunction (ED). Complications encountered post-operatively include infection, bleeding/hematoma, and device malfunction. Since the 1970s, modifications to these devices have reduced complication rates through improvement in antisepsis and design using antibiotic coatings, kink-resistant tubing, lock-out valves to prevent autoinflation, and modified reservoir shapes. Device survival and complication rates have been investigated predominately by retrospective database-derived studies. This review article focuses on the identification and management of post-operative complications following penile prosthetic and implant surgery. Etiology for ED, surgical technique, and prosthesis type are variable among studies. The most common post-operative complications of infection, bleeding, and device malfunction may be minimized by adherence to consistent technique and standard protocol. Novel antibiotic coatings and standard antibiotic regimen may reduce infection rates. Meticulous hemostasis and intraoperative testing of devices may further reduce need for revision surgery. Additional prospective studies with consistent reporting of outcomes and comparison of surgical approach and prosthesis type in patients with variable ED etiology would be beneficial. PMID:29238663

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.

Engraftment of tonsillar mononuclear cells in human skin/SCID mouse chimera--validation of a novel xenogeneic transplantation model for autoimmune diseases.

PubMed

Yamanaka, N; Yamamoto, Y; Kuki, K

2001-01-01

Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical tonsillar focal infections, based on the marked clinical improvement of the skin lesions after tonsillectomy. Despite the accumulation of data showing the clinical efficacy of tonsillectomy for this skin lesion, fundamental etiological and pathophysiological issues have yet to be addressed. One primary obstacle hindering investigators has been the lack of an appropriate animal model for this human skin disorder. In the early stage of PPP, it has been reported that lymphocytes, predominantly CD4+ T lymphocytes, infiltrate the palmar and plantar skins. However, the origin and mechanism of infiltration by these lymphocytes is not clear and there are very few reports on whether tonsillar mononuclear cells react directly with the skin. We have been intrigued by the ability to engraft human cells onto severe combined immunodeficiency (SCID) mice, together with the opportunity for long-term graft survival and ability to adoptively transfer various human immunocompetent cells. In this review, we addressed the existing deficiencies in our understanding of the relationship between tonsils and PPP by using emerging transplantation technology involving SCID mice.

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.

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...

Introversion and extroversion: implications for depression and suicidality.

PubMed

Janowsky, D S

2001-12-01

A growing body of information suggests that core or underlying personality is a significant concomitant of depression and suicidality. Introversion (ie, low extroversion) is especially promising in its relationship to the phenomenology and outcome of depression, and may represent an underlying heritable trait of etiologic significance. Furthermore, the presence of introversion has implications for differentiating unipolar and bipolar depression. It is likely that introversion acts in concert with other core personality variables, including neuroticism and having a feeling-type personality to influence depression. Considering depression from the perspective of core personality allows for novel psychotherapeutic approaches based on targeting underlying personality variables.

Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices

PubMed Central

Anholt, R. Michele; Berezowski, John; Ribble, Carl S.; Russell, Margaret L.; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%–95.4%) and specificity (85%, 95% confidence interval, 80.2%–89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use. PMID:25057893

Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors.

PubMed

Kuntsi, Jonna; Wood, Alexis C; Rijsdijk, Frühling; Johnson, Katherine A; Andreou, Penelope; Albrecht, Björn; Arias-Vasquez, Alejandro; Buitelaar, Jan K; McLoughlin, Gráinne; Rommelse, Nanda N J; Sergeant, Joseph A; Sonuga-Barke, Edmund J; Uebel, Henrik; van der Meere, Jaap J; Banaschewski, Tobias; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V; Asherson, Philip

2010-11-01

Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. An ADHD and control sibling-pair design. Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.

Using informatics and the electronic medical record to describe antimicrobial use in the clinical management of diarrhea cases at 12 companion animal practices.

PubMed

Anholt, R Michele; Berezowski, John; Ribble, Carl S; Russell, Margaret L; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%-89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.

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

Bacterial meningitic deafness: historical development of epidemiology and cellular pathology.

PubMed

Ruben, Robert

2008-04-01

Meningitis resulting in labyrinthitis and its associated hearing loss was first described by several authors during 1864 and 1865 but it was not integrated into the otological cannon until H. Knapp's publications of 1871. These reports were incorporated by St John Rossa in his textbook of 1873. Politzer, in 1882, included a fuller description of the clinical symptoms. Analysis of records of the etiologies of students in 90 schools for the deaf in North America from 1817 to 1893 showed that before the mid-1870s meningitis was rarely identified as an etiology (<1%) but by the 1880s it accounted for 10-20% of all etiologies, with male preponderance. Cellular pathology of meningitic labyrinthitis from the 1860s to the 1990s examined the ways in which bacteria invaded the inner ear. Human temporal bone studies were a major source of understanding of the pathological processes. Honda, in 1927, injected guinea pigs intracranially with live bacteria, and observed the effects on the membranous labyrinth. In 1988 Lebel's observation of the effectiveness of dexamethasone in preventing much deafness from meningitis stimulated the examination of the labyrinthine immune response. Immunological mechanisms can account for some of the variable morbidity of unilateral, progressive, less-than-severe deafness.

The Power of Theory, Research Design, and Transdisciplinary Integration in Moving Psychopathology Forward.

PubMed

Vaidyanathan, Uma; Vrieze, Scott I; Iacono, William G

While the past few decades have seen much work in psychopathology research that has yielded provocative insights, relatively little progress has been made in understanding the etiology of mental disorders. We contend that this is due to an overreliance on statistics and technology with insufficient attention to adequacy of experimental design, a lack of integration of data across various domains of research, and testing of theoretical models using relatively weak study designs. We provide a conceptual discussion of these issues and follow with a concrete demonstration of our proposed solution. Using two different disorders - depression and substance use - as examples, we illustrate how we can evaluate competing theories regarding their etiology by integrating information from various domains including latent variable models, neurobiology, and quasi-experimental data such as twin and adoption studies, rather than relying on any single methodology alone. More broadly, we discuss the extent to which such integrative thinking allows for inferences about the etiology of mental disorders, rather than focusing on descriptive correlates alone. Greater scientific insight will require stringent tests of competing theories and a deeper conceptual understanding of the advantages and pitfalls of methodologies and criteria we use in our studies.

Vertigo in Children and Adolescents: Characteristics and Outcome

PubMed Central

Gruber, Maayan; Cohen-Kerem, Raanan; Kaminer, Margalit; Shupak, Avi

2012-01-01

Objectives. To describe the characteristics and outcome of vertigo in a pediatric population. Patients. All children and adolescents presenting with vertigo to a tertiary otoneurology clinic between the years 2003–2010 were included in the study. Results. Thirty-seven patients with a mean age of 14 years were evaluated. The most common etiology was migraine-associated vertigo (MAV) followed by acute labyrinthitis/neuritis and psychogenic dizziness. Ten patients (27%) had pathological findings on the otoneurological examination. Abnormal findings were documented in sixteen of the twenty-three (70%) completed electronystagmography evaluations. Twenty patients (54%) were referred to treatment by other disciplines than otology/otoneurology. A follow-up questionnaire was filled by twenty six (70%) of the study participants. While all patients diagnosed with MAV had continuous symptoms, most other patients had complete resolution. Conclusions. Various etiologies of vertigo may present with similar symptoms and signs in the pediatric patient. Yet, variable clinical courses should be anticipated, depending on the specific etiology. This is the reason why treatment and follow up should be specifically tailored for each case according to the diagnosis. Close collaboration with other medical disciplines is often required to reach the correct diagnosis and treatment while avoiding unnecessary laboratory examinations. PMID:22272166

Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

PubMed Central

Bellomo-Brandao, Maria Angela; Escanhoela, Cecilia AF; Meirelles, Luciana R; Porta, Gilda; Hessel, Gabriel

2009-01-01

AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious, genetic-endocrine-metabolic, and idiopathic etiologies. METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum. RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n = 18), group 2 (genetic-endocrine-metabolic; n = 18), and group 3 (idiopathic; n = 50). There were no significant differences with respect to the following variables: cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis, which was more severe in group 1 (Fisher’s exact test, P = 0.016). CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a septum. PMID:19152454

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.

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...

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

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.

Shin splints--a review of terminology.

PubMed

Batt, M E

1995-01-01

This review is intended to improve the understanding of and rationale for the use of the term shin splints. Currently the term is used widely and variably, with little consensus of definition. Broadly, it denotes the occurrence of exertional lower leg pain; more specifically, it refers to an anatomical site of periostitis. The literature reports a multiplicity of descriptions and definitions of shin splints resultant from the complex etiologies and differing perceptions of these conditions. It is proposed that the term shin splint be recognized as generic, rather than diagnostic, and that specific conditions that currently exist under this term be differentiated. The etiology and interaction of these related conditions are considered, and a classification based on the current literature is given of conditions currently termed shin splints, providing a rationale for their clinical presentations, investigative findings, and interactions.

Oral mucositis: etiology, and clinical and pharmaceutical management.

PubMed

Zur, Eyal

2012-01-01

Oral mucosal damage is one of the common and worst side effects of radiotherapy and chemotherapy treatment for cancer. With prevalence between 10% and 100%, depending on the cytotoxic and/or radiotherapy regimen and patient-associated variables, this morbid condition represents a significant problem in oncology. This article addresses oral mucositis and discusses its prevalence, risk factors, clinical and economical impacts, etiology, and clinical management in view of the most recent evidence. Despite clear progress and the development of clinical guidelines on this topic, what we currently have to offer to patients to manage mucositis and oropharyngeal pain is still inadequate. This article offers two compounded preparations supported by evidence-based data to treat oral mucositis. Expansion of the knowledge of the pathogenesis of mucositis as well as a better insight into individual risk factors will provide opportunities to improve management strategies.

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.

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

Characterization of African Human Retroviruses Related to HTLV-III/LAV

DTIC Science & Technology

1988-06-15

the prototype AIDS virus , HIV -1 (4,5). This new human retrovirus has now been termed Human Immunodeficiency Virus Type...lImmunodeficiency Virus and its Relationship to the Human Immunodeficiency Viruses . Nature 32:539-543, 1987. (12) Guyader, M., Emerman, M., Sonigo, P...populations the number of AIDS cases is still quite low suggesting a distinct pathobiology to this new human retrovirus . Cohort studies of

Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study.

PubMed

Higdon, Melissa M; Le, Tham; O'Brien, Katherine L; Murdoch, David R; Prosperi, Christine; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Scott, J Anthony G; Thea, Donald M; Awori, Juliet O; Baillie, Vicky L; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N; Driscoll, Amanda J; Ebruke, Bernard E; Endtz, Hubert P; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Moore, David P; Park, Daniel E; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D; Zeger, Scott L; Deloria Knoll, Maria; Madhi, Shabir A

2017-06-15

Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the Multicenter AIDS Cohort Study

PubMed Central

Wong, Hui-Lee; Breen, Elizabeth C.; Pfeiffer, Ruth M.; Aissani, Brahim; Martinson, Jeremy J.; Margolick, Joseph B.; Kaslow, Richard A.; Jacobson, Lisa P.; Ambinder, Richard F.; Chanock, Stephen; Martínez-Maza, Otoniel; Rabkin, Charles S.

2014-01-01

Cytokine stimulation of B-cell proliferation may be an important etiologic mechanism for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). The Epstein-Barr virus may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors. We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N=160) or post-AIDS diagnosis (N=90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95 percent confidence intervals (95%CIs). Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR=0.3; 95%CI: 0.1, 0.7) but not systemically (CC vs. CT/TT: OR=1.0; 95%CI: 0.5, 1.9) (Pheterogeneity=0.03). Carriage of two copies of the “low IL10” haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend=0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0. Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important etiologic pathway for EBV-related lymphomagenesis. PMID:20299965

Prevalence of Human Immunodeficiency Virus and Sexually Transmitted Infections Among Cisgender and Transgender Women Sex Workers in Greater Kuala Lumpur, Malaysia: Results From a Respondent-Driven Sampling Study.

PubMed

Wickersham, Jeffrey A; Gibson, Britton A; Bazazi, Alexander R; Pillai, Veena; Pedersen, Courtney J; Meyer, Jaimie P; El-Bassel, Nabila; Mayer, Kenneth H; Kamarulzaman, Adeeba; Altice, Frederick L

2017-11-01

Sex workers face a disproportionate burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STI) worldwide. For cisgender women sex workers (CWSW), global HIV prevalence is over 10%, whereas transgender women sex workers (TWSW) face an HIV burden of 19% to 27%. We used respondent-driven sampling to recruit 492 sex workers, including CWSW (n = 299) and TWSW (n = 193) in Greater Kuala Lumpur, Malaysia. Participants completed an in-depth survey and were screened for HIV, syphilis, Chlamydia trachomatis, and Neisseria gonorrhoeae. Sample characteristics stratified by gender identity and interview site are presented. Bivariate analyses comparing CWSW and TWSW were conducted using independent samples t tests for continuous variables and χ tests for categorical variables. Pooled HIV prevalence was high (11.7%; 95% confidence interval [CI], 8.8-14.5), and was similar for CWSW (11.1%) and TWSW (12.4%). Rates of syphilis 25.5% (95% CI, 21.6-29.5), C. trachomatis (14.8%; 95% CI, 11.6-18.0) and N. gonorrhoeae (5.8%; 95% CI, 3.7-7.9) were also concerning. Both groups reported lifetime HIV testing (62.4%), but CWSW were less likely to have ever been HIV tested (54.5%) than TWSW (74.6%). Median time since last HIV test was 24 months. Previous screening for STI was low. Inconsistent condom use and drug use during sex work were not uncommon. High HIV and STI prevalence, coupled with infrequent HIV and STI screening, inconsistent condom use, and occupational drug use, underscore the need for expanded HIV and STI prevention, screening, and treatment efforts among CWSW and TWSW in Malaysia.

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.

Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation.

PubMed

Friedmann, David; Keller, Baerbel; Harder, Ina; Schupp, Jonas; Tanriver, Yakup; Unger, Susanne; Warnatz, Klaus

2017-11-01

Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc). We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype. Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21 low B cells, but we could not detect an association of the altered ILC phenotype with a T H 1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients. We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21 low B cells, but not overtly with the relative expansion of T H 1-like T cells. Given the relative abundance of T H 1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.

Anal Dysplasia Screening and Treatment in a Southern Human Immunodeficiency Virus Clinic.

PubMed

Willeford, Wesley G; Barroso, Luis; Keller, Jennifer; Fino, Nora; Bachmann, Laura H

2016-08-01

Persistent human papillomavirus infection in human immunodeficiency virus (HIV)-infected individuals has been strongly associated with anal squamous cell carcinoma. The incidence of anal squamous cell carcinoma continues to increase in this population despite advances in HIV therapy. There are few studies describing the prevalence of anal cancer precursors, treatment outcomes, and associated factors among HIV-infected populations in the southern United States. A retrospective chart review was performed on 355 HIV-infected patients from a Southern HIV clinic who were 18 years or older and had received at least one anal Pap smear. Demographic and clinical variables were collected. Descriptive statistics, single variable, and multivariate logistic regression analysis were performed to evaluate for predictors of high-grade squamous intraepithelial lesion (HSIL). Odds ratios and 95% confidence intervals were constructed for independent measures. After the first anal Pap smear, 38.3% (70/183) of patients with abnormal results were lost to follow-up. Comparing patients with biopsy proven HSIL versus low-grade squamous intraepithelial lesions, patients were less likely to have HSIL if they had a higher CD4 count (odds ratio, 0.81; 95% confidence interval, 0.72-0.93; P = 0.0022). Treatment success after the first round of treatment for topical and infrared coagulation therapy was 36.7% (18/49, all therapy types), and of those who achieved biopsy proven treatment success at follow-up screening, 94.4% (17/18) required subsequent therapy. Patients with a higher CD4 count were less likely to have HSIL. CD4 nadir, number of sexual partners, and race/ethnicity were not significantly associated with the presence of HSIL.

Loss of Asparagine-Linked Glycosylation Sites in Variable Region 5 of Human Immunodeficiency Virus Type 1 Envelope Is Associated with Resistance to CD4 Antibody Ibalizumab ▿

PubMed Central

Toma, Jonathan; Weinheimer, Steven P.; Stawiski, Eric; Whitcomb, Jeannette M.; Lewis, Stanley T.; Petropoulos, Christos J.; Huang, Wei

2011-01-01

Ibalizumab (formerly TNX-355) is a first-in-class, monoclonal antibody inhibitor of CD4-mediated human immunodeficiency type 1 (HIV-1) entry. Multiple clinical trials with HIV-infected patients have demonstrated the antiviral activity, safety, and tolerability of ibalizumab treatment. A 9-week phase Ib study adding ibalizumab monotherapy to failing drug regimens led to transient reductions in HIV viral loads and the evolution of HIV-1 variants with reduced susceptibility to ibalizumab. This report characterizes these variants by comparing the phenotypic susceptibilities and envelope (env) sequences of (i) paired baseline and on-treatment virus populations, (ii) individual env clones from selected paired samples, and (iii) env clones containing site-directed mutations. Viruses with reduced susceptibility to ibalizumab were found to exhibit reduced susceptibility to the anti-CD4 antibody RPA-T4. Conversely, susceptibility to soluble CD4, which targets the HIV-1 gp120 envelope protein, was enhanced. No changes in susceptibility to the fusion inhibitor enfuvirtide or the CCR5 antagonist maraviroc were observed. Functionally, viruses with reduced ibalizumab susceptibility also displayed high levels of infectivity relative to those of paired baseline viruses. Individual env clones exhibiting reduced ibalizumab susceptibility contained multiple amino acid changes in different regions relative to the paired baseline clones. In particular, clones with reduced susceptibility to ibalizumab contained fewer potential asparagine-linked glycosylation sites (PNGSs) in variable region 5 (V5) than did paired ibalizumab-susceptible clones. The reduction in ibalizumab susceptibility due to the loss of V5 PNGSs was confirmed by site-directed mutagenesis. Taken together, these findings provide important insights into resistance to this new class of antiretroviral drug. PMID:21289125

Nutritional status and CD4 cell counts in patients with HIV/AIDS receiving antiretroviral therapy.

PubMed

Santos, Ana Célia Oliveira dos; Almeida, Ana Maria Rampeloti

2013-01-01

Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4) cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%). Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) 17.0 software for Windows. Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.

Variables influencing anti-human immunodeficiency virus type 1 neutralizing human monoclonal antibody (NhMAb) production among infected Thais.

PubMed

Akapirat, Siriwat; Avihingsanon, Anchalee; Ananworanich, Jintanat; Schuetz, Alexandra; Ramasoota, Pongrama; Luplertlop, Natthanej; Ono, Ken-Ichiro; Ikuta, Kazuyoshi; Utachee, Piraporn; Kameoka, Masanori; Leaungwutiwong, Pornsawan

2013-09-01

We conducted this study to determine the clinical variables associated with the production of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 01_AE neutralizing human monoclonal antibodies (NhMAbs) using a hybridoma technique. This cross sectional study was performed in 20 asymptomatic HIV-1-infected Thais. Peripheral blood mononuclear cells (PBMCs) were obtained from each study participant and fused with SPYMEG cells. Culture supernatant collected from growing hybridomas was tested for neutralizing activity against HIV-1 CRF01_AE Env-recombinant viruses. Fifty hybridomas expressing anti-HIV-1 NhMAbs with strong neutralizing activity against at least 1 CRF01_AE Env-recombinant virus were found. A positive association between the numbers of hybridomas produced and the CD4 counts of study participants (p = 0.019) was observed. NhMAb-producing hybridomas with strong neutralizing activity were mostly found in participans diagnosed with HIV-1 infection within the previous 1 year. The HIV-1 viral load was not significantly correlated with the numbers of either established hybridomas or clones expressing anti-HIV-1 NhMAbs with strong neutralizing activity. To our knowledge, this is the first study of NhMAb-producing hybridomas obtained from HIV-1 CRF01_AE-infected populations identified by antibody binding to HIV-1 V3 loop peptide enzyme-linked immunosorbent assay (ELISA) or TRUGENE HIV-1 Genotyping Assay (HIV-1 pol sequence). It provides important criterion to slect study participants with high CD4 counts who produce large numbers of hybridoma clones. The results are valuable for further studies related to nurtalizing antibodies production and HIV-1 vaccine development.

Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome.

PubMed

Guffroy, Aurélien; Mourot-Cottet, Rachel; Gérard, Laurence; Gies, Vincent; Lagresle, Chantal; Pouliet, Aurore; Nitschké, Patrick; Hanein, Sylvain; Bienvenu, Boris; Chanet, Valérie; Donadieu, Jean; Gardembas, Martine; Karmochkine, Marina; Nove-Josserand, Raphaele; Martin, Thierry; Poindron, Vincent; Soulas-Sprauel, Pauline; Rieux-Laucat, Fréderic; Fieschi, Claire; Oksenhendler, Eric; André-Schmutz, Isabelle; Korganow, Anne-Sophie

2017-10-01

Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*10 6 /L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21 low CD38 low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

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

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome

PubMed Central

Monaco, Cynthia L.; Gootenberg, David B.; Zhao, Guoyan; Handley, Scott A.; Ghebremichael, Musie S.; Lim, Efrem S.; Lankowski, Alex; Baldridge, Megan T.; Wilen, Craig B.; Flagg, Meaghan; Norman, Jason M.; Keller, Brian C.; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Siedner, Mark J.; Kwon, Douglas S.; Virgin, Herbert W.

2016-01-01

SUMMARY Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. PMID:26962942

Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs

PubMed Central

Basel, Matthew T.; Balivada, Sivasai; Beck, Amanda P.; Kerrigan, Maureen A.; Pyle, Marla M.; Dekkers, Jack C.M.; Wyatt, Carol R.; Rowland, Robert R.R.; Anderson, David E.; Bossmann, Stefan H.

2012-01-01

Abstract Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodeficient pigs were injected subcutaneously in the left ear with human melanoma cells (A375SM cells) and in the right ear with human pancreatic carcinoma cells (PANC-1). All immunodeficient pigs developed tumors that were verified by histology and immunohistochemistry. Nonaffected littermates did not develop tumors. Immunodeficient pigs, which do not reject xenografted human tumors, have the potential to become an extremely useful animal model for cancer therapy because of their similarity in size, anatomy, and physiology to humans. PMID:23514746

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

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

PubMed

Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

2016-03-09

Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization.

PubMed

Yamamoto, Hiroyuki; Matano, Tetsuro

2016-01-01

Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses. Sufficient sub-sterile NAb titers after established infection also confer dose-dependent reduction of viremia, and in certain earlier time frames augment adaptive immune cell responses and even provide rebound-free viral control. Here, we provide an overview of the obtained patterns of SIV/SHIV protection and viral control by various types of NAb passive immunizations and discuss how these notions may be extrapolated to NAb-based clinical control of HIV infection.

Prevalence of Anal Dysplasia in Human Immunodeficiency Virus-Infected Transgender Women.

PubMed

Kobayashi, Takaaki; Sigel, Keith; Gaisa, Michael

2017-11-01

Although human immunodeficiency virus-infected men who have sex with men are at high risk for anal cancer, little is known about the prevalence of anal dysplasia in human immunodeficiency virus (HIV)-infected transgender women. Our study found that prevalence rates of abnormal anal cytology and histology in HIV-infected transgender women were similar to those in HIV-infected men who have sex with men.

Immunologic Intervention in HIV Infection: Anti-Polymerase Responses and Hormonal Regulation

DTIC Science & Technology

1993-09-01

chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3/enhancer element. J...Grimison B, Gonenne A. 1992. Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. Blood 79...Kong X-B, Chou T-C. Interactions of recombinant human growth hormone with dideoxynucleoside inhibitors of human immunodeficiency virus. Blood, in

An update on gain-of-function mutations in primary immunodeficiency diseases.

PubMed

Jhamnani, Rekha D; Rosenzweig, Sergio D

2017-12-01

Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations. The more recent developments related to gain-of-function primary immunodeficiencies mostly involving increased infection susceptibility but also immune dysregulation and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms, different mutation types, clinical features, laboratory markers, current and potential new treatments on patients with caspase recruitment domain family member 11, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit 1, chemokine C-X-C motif receptor 4, sterile α motif domain containing 9-like, and nuclear factor κ-B subunit 2 gain-of-function mutations are reviewed for each disease. With the identification of gain-of-function mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms unveiled and new-targeted therapeutic approaches can be explored as potential rescue treatments for these diseases.

Maternal serum alpha-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus.

PubMed

Gross, Susan; Castillo, Wilfrido; Crane, Marilyn; Espinosa, Bialines; Carter, Suzanne; DeVeaux, Richard; Salafia, Carolyn

2003-04-01

The purpose of this study was to establish whether there is a correlation between maternal serum genetic screen analyte results in pregnant women with human immunodeficiency virus and corresponding human immunodeficiency virus index values. Medical records of all pregnant women with human immunodeficiency virus who were delivered at Bronx Lebanon Hospital Center from January 2000 through December 2001 were reviewed for maternal serum screen results, viral load, CD4 counts and percent, antiretroviral therapy, opportunistic infections, substance abuse, and other demographic data. Statistical analysis was accomplished with the chi(2) test, Mann-Whitney U test, and Spearman rank correlation test, with a probability value of <.05 considered significant. Of the 98 women with human immunodeficiency virus who were delivered, 49 women (50%) had a maternal serum genetic screen available. Screened and unscreened women had similar severity of human immunodeficiency virus disease, CD4 count and percentage, and viral loads. Serum screen results showed elevations in maternal serum human chorionic gonadotropin (1.43 +/- 1.04 multiples of the median [MoM]; range, 0.2-5.2 MoM) and maternal serum alpha-fetoprotein (1.29 +/- 0.9 MoM; range, 0.5-3.3 MoM) compared with expected values in the general obstetric population. Maternal serum human chorionic gonadotropin was correlated inversely with CD4 count (P =.002) and CD4 percent (P <.0001). Maternal serum alpha-fetoprotein varied directly with viral load (P <.0001). Increasing maternal serum human chorionic gonadotropin and maternal serum alpha-fetoprotein levels in patients with human immunodeficiency virus are correlated with increasing viral load and decreasing CD4 counts.

Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

2017-08-02

The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral treatment showed the worst hearing threshold) and seemed to have lower neuroelectric transmission speed along the auditory pathway in the brainstem, subcortical and cortical regions. Copyright © 2017. Published by Elsevier Editora Ltda.

A conceptual model of factors contributing to the development of muscle dysmorphia.

PubMed

Grieve, Frederick G

2007-01-01

Muscle dysmorphia is a recently described subcategory of Body Dysmorphic Disorder. It is most prevalent in males and has a number of cognitive, behavioral, socioenviornmental, emotional, and psychological factors that influence its expression. An etiological model describing these influences is presented for evaluation. Nine variables (body mass, media influences, ideal body internalization, low self-esteem, body dissatisfaction, health locus of control, negative affect, perfectionism, and body distortion) were identified through the use of extant literature on muscle dysmorphia and through extrapolation from literature involving women and eating disorders. The functional relationships among these variables are described and implications of the model are discussed.

Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

PubMed Central

Roshorm, Yaowaluck; Bridgeman, Anne; Létourneau, Sven; Liljeström, Peter; Potash, Mary Jane; Volsky, David J.; McMichael, Andrew J.; Hanke, Tomáš

2011-01-01

Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans. PMID:21625575

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.

Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing.

PubMed

Tran, Sheri; Deacon, Naomi; Minokadeh, Anushirvan; Malhotra, Atul; Davis, Daniel P; Villanueva, Sheri; Sell, Rebecca E

2016-10-01

Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2-7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2-7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p<0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p<0.001) while arrests due to dysrhythmia had the opposite trend (p=0.014). Rates of survival to discharge (p=0.038) and favorable neurological outcomes (p=0.002) were lower with increasing hospital days while ROSC was not different among the groups (p=0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0-45.7%], p=0.002 vs HD2-7: 34.0% [95% CI, 27.5-40.4%], p<0.001 vs HD>7: 27.2% [95% CI, 21.4-33.0%], p<0.001). The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing☆,☆☆,★

PubMed Central

Tran, Sheri; Deacon, Naomi; Minokadeh, Anushirvan; Malhotra, Atul; Davis, Daniel P.; Villanueva, Sheri; Sell, Rebecca E.

2017-01-01

Objective Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. Subject and methods Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2–7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. Results A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2–7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p < 0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p < 0.001) while arrests due to dysrhythmia had the opposite trend (p = 0.014). Rates of survival to discharge (p = 0.038) and favorable neurological outcomes (p = 0.002) were lower with increasing hospital days while ROSC was not different among the groups (p = 0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0–45.7%], p = 0.002 vs HD2–7: 34.0% [95% CI, 27.5–40.4%], p < 0.001 vs HD>7: 27.2% [95% CI, 21.4–33.0%], p < 0.001). Conclusions The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication. PMID:27456394

Bronchiectasis: Current Concepts in Pathogenesis, Immunology, and Microbiology.

PubMed

Boyton, Rosemary J; Altmann, Daniel M

2016-05-23

Bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. This suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. The damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. Lung infection is caused by respiratory bacterial and fungal pathogens, including Pseudomonas aeruginosa, Haemophilus, Aspergillus fumigatus, and nontuberculous mycobacteria. Recent studies have highlighted the relationship between the lung microbiota and microbial-pathogen niches. Disease may result from environments favoring interleukin-17-driven neutrophilia. Bronchiectasis may present in autoimmune disease, as well as conditions of immune dysregulation, such as combined variable immune deficiency, transporter associated with antigen processing-deficiency syndrome, and hyperimmunoglobulin E syndrome. Differences in prevalence across geography and ethnicity implicate an etiological mix of genetics and environment underpinning susceptibility.

A Unifying Theory of Biological Function.

PubMed

van Hateren, J H

2017-01-01

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism's fitness, and modulates the organism's variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories.

[Poland's syndrome].

PubMed

Slezak, R; Sasiadek, M

2000-08-01

Poland's syndrome consists of the variable clinical features, but always includes unilateral aplasia of the chest wall muscles and ipsilateral anomalies of upper extremity. The incidence of Poland's syndrome, reported by different authors ranges from 1:10,000 to 1:100,000 and is observed more frequently in males than in females with the right side of the body affected more often than the left. The etiology of this syndrome is still discussed. However most of described cases were sporadic, rare familial incidence of Poland's syndrome were also presented. Therefore different etiologic factors of the Poland's syndrome are taken into account: genetic, vascular compromise during early stages of embriogenesis but also teratogenic effect of environmental xenobiotics (e.g. cigarette smoking by pregnant women). The authors present also the case of 20-years old man with inherited bilateral syndactyly with the right side aplasia of major pectoralis muscle and face asymmetry. The familial history was negative in respect to the features, associated with Poland's syndrome.

Glaucoma and Corneal Transplant Procedures

PubMed Central

Al-Mahmood, Ammar M.; Al-Swailem, Samar A.; Edward, Deepak P.

2012-01-01

Glaucoma after corneal transplantation is a leading cause of ocular morbidity after penetrating keratoplasty. The incidence reported is highly variable and a number of etiologic factors have been identified. A number of treatment options are available; surgical intervention for IOP control is associated with a high incidence of graft failure. IOP elevation is less frequently seen following deep anterior lamellar keratoplasty. Descemet's striping-automated endothelial keratoplasty is also associated with postprocedure intraocular pressure elevation and secondary glaucoma and presents unique surgical challenges in patients with preexisting glaucoma surgeries. Glaucoma exists in up to three-quarters of patients who undergo keratoprosthesis surgery and the management if often challenging. The aim of this paper is to highlight the incidence, etiology, and management of glaucoma following different corneal transplant procedures. It also focuses on the challenges in the diagnosis of glaucoma and intraocular pressure monitoring in this group of patients. PMID:22315661

Cancer: Bad Luck or Punishment?

PubMed

Lichtenstein, A V

2017-01-01

Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The correlation between the lifetime risk of several types of cancer and the total number of divisions of normal self-renewing cells revealed by the authors has given them grounds to put forward the "bad luck" hypothesis. It assumes that ~70% of cancer variability is attributed to random errors arising during DNA replication in normal, noncancerous stem cells, i.e. to internal factors, which is impossible either to expect or to prevent. This assumption caused many critical responses that emphasize, on the contrary, the defining role of extrinsic factors in cancer etiology. The analysis of epidemiological and genetic data presented in this work testifies in favor of the "bad luck" hypothesis.

Occupational Stress: A Comprehensive Review of the Top 50 Annual and Lifetime Cited Articles.

PubMed

Nowrouzi, Behdin; Nguyen, Christine; Casole, Jennifer; Nowrouzi-Kia, Behnam

2017-05-01

This study determined the impact and influence of published articles on the field of occupational stress. A transdisciplinary approach was used to identify the 50 work-related stress articles with the most lifetime citations and the 50 work-related stress articles with the highest annual citation rates. Studies were categorized based on their primary focus: (a) etiology, (b) predictor of outcome for which occupational stress is the outcome or predictor of outcome for which occupational stress is an independent variable, (c) management/intervention, (d) theory/model/framework, or (e) methodologies. The majority of studies with the highest number of lifetime citations as well as the highest annual citation rates used stress as a predictor or outcome of another factor. The proportion of studies that were categorized by etiology, intervention/management, theory/model/framework, or methodologies was relatively low for both lifetime and annual citations.

Advances in Autism

PubMed Central

Geschwind, Daniel H.

2013-01-01

Autism is a common childhood neurodevelopmental disorder with strong genetic liability. It is not a unitary entity but a clinical syndrome, with variable deficits in social behavior and language, restrictive interests, and repetitive behaviors. Recent advances in the genetics of autism emphasize its etiological heterogeneity, with each genetic susceptibility locus accounting for only a small fraction of cases or having a small effect. Therefore, it is not surprising that no unifying structural or neuropathological features have been conclusively identified. Given the heterogeneity of autism spectrum disorder (ASD), approaches based on studying heritable components of the disorder, or endophenotypes, such as language or social cognition, provide promising avenues for genetic and neurobiological investigations. Early intensive behavioral and cognitive interventions are efficacious in many cases, but autism does not remit in the majority of children. Therefore, development of targeted therapies based on pathophysiologically and etiologically defined subtypes of ASD remains an important and achievable goal of current research. PMID:19630577

Unconsummated marriage in sub-Saharan Africa: case reports.

PubMed

Lema, Valentino M

2014-09-01

Unconsummated marriage is a condition where newly married couples are unable to achieve penile-vaginal intercourse for variable periods despite desire and several attempts to do so. Its exact cause(s) is/are unknown, but performance anxiety resulting from or leading to other conditions is reportedly the major etiological factor. It is thought to be more prevalent in traditional and conservative religious communities where premarital sexual exposure is strictly prohibited. Most publications on unconsummated marriage have originated from North America, European and Middle Eastern countries. There have not been any such reports from sub-Saharan Africa, which is home to diverse cultures and traditions regarding premarital sex and marriage. This paper presents a sample of four cases with unconsummated marriage managed by the author in his private clinic based in the city of Nairobi Kenya, over the past five years. Possible etiological factors and management approaches are discussed, with a review of relevant literature.

[Cardiac sarcoidosis - clinical manifestation and diagnosis].

PubMed

Błaut-Jurkowska, Justyna; Podolec, Piotr; Olszowska, Maria

2016-08-01

Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of noncaseating granulomas. The etiology of sarcoidosis remains unknown. Heart involvement in the course of sarcoidosis concerns about 5% of patients. The most common manifestation of cardiac sarcoidosis are conduction abnormalities, arrhythmias and heart failure. The diagnostic algorithm includes performing a clinical history, a 12-lead electrocardiogram (ECG) and an echocardiogram. If any of the initial screening investigations yields an abnormality, diagnostics should be continue using advanced imaging techniques: cardiovascular magnetic resonance (CMR) or fluorodeoxyglucose positron emission tomography (FDG-PET). Nowadays endomyocardial biopsy is not performed routinely.The clinical picture of cardiac sarcoidosis is highly variable. Screening for cardiac sarcoidosis should be performed in all patients diagnosed with extracardiac sarcoidosis. Cardiac sarcoidosis should also be suspected in young patients without a diagnosis of sarcoidosis who present with conduction abnormalities of unknown etiology, because cardiac sarcoidosis may be the first or the only manifestation of the disease. © 2016 MEDPRESS.

Enhancing sequential time perception and storytelling ability of deaf and hard of hearing children.

PubMed

Ingber, Sara; Eden, Sigal

2011-01-01

A 3-month intervention was conducted to enhance the sequential time perception and storytelling ability of young children with hearing loss. The children were trained to arrange pictorial episodes of temporal scripts and tell the stories they created. Participants (N = 34, aged 4-7 years) were divided into 2 groups based on whether their spoken-language gap was more or less than 1 year compared to age norms. They completed A. Kaufman and N. Kaufman's (1983) picture series subtest and Guralnik's (1982) storytelling test at pretest and posttest. Measures demonstrated significant improvement in sequential time and storytelling achievement postintervention. Three of the examined demographic variables revealed correlations: Participants with genetic etiology showed greater improvement in time sequencing and storytelling than participants with unknown etiology; early onset of treatment correlated with better achievement in time sequencing; cochlear implant users showed greater storytelling improvement than hearing aid users.

Appearance of hyperostosis frontalis interna in some osteoarcheological series from Hungary.

PubMed

Hajdu, T; Fóthi, E; Bernert, Zs; Molnár, E; Lovász, G; Kovári, I; Köhler, K; Marcsik, A

2009-01-01

Hyperostosis frontalis interna (HFI) is a generalised pathological condition with an unknown etiology and variable clinical association. It is characterized by excess bone growth and manifested on the inner table of the frontal bone, occasionally extending onto the temporals, parietals and the occipital. The etiology of HFI is uncertain: it may be an unknown genetic predisposition, a common environmental exposure, or special metabolic diseases. The purpose of the present study is to report cases of HFI in some osteoarcheological series from Hungary and to emphasize the importance of the investigation of HFI in ancient populations. Twenty out of 803 adults with observable frontal bones exhibited HFI, ranging from early to mid-type, including 15 females and 5 males. Some overgrowths with edges were blending into the endocranial surface, and some were prominently protruding from the surface. Advanced cases of HFI (type C) were observed after age 40-60 years.

[Autism spectrum disorder: Etiological, diagnostic and therapeutic aspects].

PubMed

Reynoso, César; Rangel, María José; Melgar, Virgilio

2017-01-01

Autism spectrum disorder (ASD) was described for the first time in 1943 by Leo Kanner, and since 2004, 18 490 articles in the subject have been published, which in turn have been cited 48 416 times.1 Almost half of these publications come from the United States of America and the vast maority of the efforts to improve the quality of life of these patients have taken place in developed countries. This disorder consists of an inability to acquire social and emotional skills during early development that progressively results in variable degrees of social adaptation discapacity. The etiology is multifactorial and includes functional and structural neurological abnormalities, some of them with putative genetic and/or epigenetic origin. There is an alarming lack of knowledge in the subject among health care professionals. The purpose of this systematic review is to summarize the most relevant historical, diagnostic and therapeutic aspects of ASD.

Moral reasoning of Piagetian-matched retarded and nonretarded children and adolescents.

PubMed

Kahn, J V

1983-09-01

The moral reasoning of four IQ/etiology groups was investigated: 19 organically abnormal moderately retarded, 19 organically abnormal mildly retarded, 19 mildly retarded due to psychosocial disadvantage, and 19 nonretarded individuals. In each group 12 Ss were preoperational and seven concrete operational. Moral reasoning was assessed by an instrument using moral dilemmas based on Kohlberg's procedures. The Slosson Intelligence Test was used to determine the IQs and mental ages of each S. Piagetian stage was determined with the standard conservation of number tasks. The findings indicated no overall significant differences between the mildly retarded and the nonretarded Ss or between the mildly retarded and the moderately retarded Ss, but differences were found between the moderately retarded and the nonretarded Ss. A significant interaction was found between the two independent variables, IQ/etiology and cognitive level. The results were discussed as supporting Zigler's development position and as damaging to Kohlberg's position.

Sarcoidosis with prominent necrosis on histopathology.

PubMed

Rosenstein, Rachel; Orme, Charisse; Kim, Randie H; Meehan, Shane A; Femia, Alisa

2016-12-15

Sarcoidosis is a multiorgan inflammatory diseasewith variable clinical presentations and the commonhistopathologic finding of noncaseating granulomas.The etiology of the disease is not known, butevidence suggests both environmental and geneticcontributions to the pathogenesis. Depending onthe severity of cutaneous disease and extent ofextracutaneous involvement, therapies range fromtopical and intralesional glucocorticoids to systemicimmunomodulatory and immunosuppressiveagents. We present the case of a patient withcutaneous sarcoidosis with prominent necrosis onhistopathologic examination in the setting of severepulmonary sarcoidosis.

Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity

NASA Astrophysics Data System (ADS)

Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

1992-06-01

In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

Immune deficiency as a risk factor in Epstein-Barr virus-induced malignant diseases.

PubMed Central

Purtilo, D T; Okano, M; Grierson, H L

1990-01-01

Epstein-Barr virus (EBV) is a ubiquitous DNA virus that normally infects silently, establishing lifelong latency. Substantial empirical observations support the view that immunodeficiency is permissive in EBV-induced lymphoproliferative diseases (LPD). Primary immune deficient patients such as those with X-linked lymphoproliferative disease and individuals with acquired immune deficiency secondary to immunosuppressive drugs for organ transplantation or individuals infected with human immunodeficiency virus are also at very high risk for lethal LPD. The importance of immunodeficiency and EBV in the development of head and neck carcinomas and uterine cervical carcinoma is less clear. Methods are available for detecting immunodeficiency and EBV genome and thus preventive strategies are being developed to preclude LPD from occurring. PMID:2176975

Malnutrition and Cachexia in Heart Failure.

PubMed

Rahman, Adam; Jafry, Syed; Jeejeebhoy, Khursheed; Nagpal, A Dave; Pisani, Barbara; Agarwala, Ravi

2016-05-01

Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients. © 2015 American Society for Parenteral and Enteral Nutrition.

Sexual behavior differences between amphetamine-type stimulants users and heroin users.

PubMed

Jia, Zhen-jun; Yan, Shi-yan; Bao, Yan-ping; Lian, Zhi; Zhang, Hao-ran; Liu, Zhi-min

2013-01-01

To explore the sexual behavior of amphetamine-type stimulant (ATS) users and heroin users, and to find out the dangerous sexual behaviors, even related risk factors among them. Four hundred thirty-eight ATS users and 524 heroin users were recruited in 10 compulsory detoxification treatment centers and voluntary detoxification centers in Beijing, Shenzhen, Guangzhou, Xi'an, and Taiyuan. Their sociodemographic characteristics, history of drug taking, and sexual behaviors were surveyed. Many variables of sociodemographic characteristics and sexual behaviors were significantly different between ATS users and heroin users (P < 0.05). Dangerous sexual behaviors among ATS users include sexual intercourse often or each time after taking drug (30.1%), multiple sexual intercourse (16.5%), casual sex partners (34.0%), homosexual partners (2.5%), and never or occasionally using condom with a steady sex partner (79.3%) or with casual sex partners (39.1%). The rate of ever-infecting sexually transmitted disease (STD) was high in both the groups (ATS, 20.5%; heroin, 30.9%). Sexual behavior is the main way to transmit STD and human immunodeficiency virus among ATS users. The study results will promote the government's awareness of the issue and take necessary steps to slow the spread of STD and human immunodeficiency virus among the ATS users.

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

PubMed

Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

1996-06-01

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression

PubMed Central

1990-01-01

Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF- kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection. PMID:2193097

Turkish and American Undergraduate Students' Attitudes Toward HIV/AIDS Patients: A Comparative Study.

PubMed

Atav, A Serdar; Sendir, Merdiye; Darling, Rosa; Acaroglu, Rengin

2015-01-01

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a complex healthcare problem. Research has demonstrated that negative attitudes affect healthcare provision. The purpose of this study was to compare nursing students' attitudes using the AIDS Attitude Scale (AAS). A descriptive, cross-sectional study was conducted in nursing schools in Istanbul, Turkey, and in Upstate New York (NY). Baccalaureate nursing students (n = 613) from both countries completed the questionnaire. Demographic data, overall AAS attitudes, and attitudes within each subscale were compared. Analyses included frequency and percentages of the grouped variables, arithmetic means and standard deviations, t-test for independent samples, and multiple analysis of variance. Upstate NY students' mean total AAS scores were significantly more positive toward HIV+ patients than Turkish students'. Scores for Professional Resistance and Emotions subscales were significantly more positive for the Upstate NY students, but Fear of Contagion was not. Upstate NY students had more negative attitudes in the contexts of job risk and eating in a restaurant where the chef has AIDS; more professional resistance to referring patients and training specialists for HIV/AIDS patients; and lower tender feelings for people with HIV/AIDS (p < .01 for each). Improvement in students' attitudes is beneficial for promoting nonjudgmental, compassionate care for the HIV+ population. © 2014 Wiley Periodicals, Inc.

Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences

PubMed Central

Brander, Christian; Yang, Otto O.; Jones, Norman G.; Lee, Yun; Goulder, Philip; Johnson, R. Paul; Trocha, Alicja; Colbert, David; Hay, Christine; Buchbinder, Susan; Bergmann, Cornelia C.; Zweerink, Hans J.; Wolinsky, Steven; Blattner, William A.; Kalams, Spyros A.; Walker, Bruce D.

1999-01-01

Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences. PMID:10559335

Specific CD8+ T Cell Responses Correlate with Control of Simian Immunodeficiency Virus Replication in Mauritian Cynomolgus Macaques

PubMed Central

Budde, Melisa L.; Greene, Justin M.; Chin, Emily N.; Ericsen, Adam J.; Scarlotta, Matthew; Cain, Brian T.; Pham, Ngoc H.; Becker, Ericka A.; Harris, Max; Weinfurter, Jason T.; O'Connor, Shelby L.; Piatak, Michael; Lifson, Jeffrey D.; Gostick, Emma; Price, David A.; Friedrich, Thomas C.

2012-01-01

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8+ T cells, but it is not clear whether particular CD8+ T cell responses or a broad repertoire of epitope-specific CD8+ T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth. PMID:22573864

Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) case reporting in the World Health Organization European Region in 2006.

PubMed

Devaux, I; Alix, J; Likatavicius, G; Herida, M; Nielsen, S S; Hamers, F F; Nardone, A

2008-09-25

This article presents information on HIV and AIDS case reporting systems as part of a survey on HIV/AIDS surveillance practices in the World Health Organization (WHO) European Region. A standardised questionnaire was sent to the 53 national correspondents of the European Centre for the Epidemiological Monitoring of AIDS(EuroHIV). The HIV and AIDS case reporting section of the questionnaire comprised four parts: data collection system, HIV/AIDS case definition for surveillance, variables collected, and evaluation of surveillance systems). Individual-based data collection systems for HIV case reports have been implemented in 43 of 44 countries in the WHO European Region and for AIDS case reports in all the countries. For HIV case reports, a coded identifier is used in 28 countries, and full names are used in 11 countries. The European AIDS case definition has been adopted in 35 countries(80%). Information on molecular epidemiology is available in 30 countries, and HIV drug resistance is monitored in 11 countries.HIV/AIDS case reporting systems have been evaluated for underreporting in 17 countries and for completeness in 11 countries.This article outlines the future needs for HIV/AIDS surveillance and presents recommendations on how to improve data comparability across European countries in the WHO region.

Women and major depressive disorder: clinical perspectives on causal pathways.

PubMed

Accortt, Eynav Elgavish; Freeman, Marlene P; Allen, John J B

2008-12-01

Epidemiological data on the prevalence of mood disorders demonstrate that major depressive disorder (MDD) is approximately twice as common in women as in men and that its first onset peaks during the reproductive years. We aimed to review key social, psychological, and biological factors that seem strongly implicated in the etiology of major depression and to focus on sex-specific aspects of depression, such as the role of a woman's reproductive life cycle in depressive symptomatology. A review of the literature, from 1965 to present, was conducted. An integrated etiological model best explains gender and sex differences in depression. Social, psychological, and biological variables must be simultaneously taken into account. These vulnerabilities include (but are not limited to) gender-specific roles in society, life stress such as trauma, a tendency toward ruminative coping strategies, and the effects of sex hormones and genetic factors. To effectively treat MDD in women and to prevent the recurrence of illness in vulnerable women, clinicians must understand the sex-specific aspects of mood disorders over the longitudinal course of women's reproductive lives. A biopsychosocial approach should, therefore, be the main focus of future research and practice, to eventually result in an integrated etiological model of depression in women. Based on the prevalence of MDD in women, timely screening, diagnosis, and intervention should be public health priorities.

Romantic Relationship Satisfaction Moderates the Etiology of Adult Personality.

PubMed

South, Susan C; Krueger, Robert F; Elkins, Irene J; Iacono, William G; McGue, Matt

2016-01-01

The heritability of major normative domains of personality is well-established, with approximately half the proportion of variance attributed to genetic differences. In the current study, we examine the possibility of gene × environment interaction (G×E) for adult personality using the environmental context of intimate romantic relationship functioning. Personality and relationship satisfaction are significantly correlated phenotypically, but to date no research has examined how the genetic and environmental components of variance for personality differ as a function of romantic relationship satisfaction. Given the importance of personality for myriad outcomes from work productivity to psychopathology, it is vital to identify variables present in adulthood that may affect the etiology of personality. In the current study, quantitative models of G×E were used to determine whether the genetic and environmental influences on personality differ as a function of relationship satisfaction. We drew from a sample of now-adult twins followed longitudinally from adolescence through age 29. All participants completed the Multidimensional Personality Questionnaire (MPQ) and an abbreviated version of the Dyadic Adjustment Scale. Biometric moderation was found for eight of the eleven MPQ scales examined: well-being, social potency, negative emotionality, alienation, aggression, constraint, traditionalism, and absorption. The pattern of findings differed, suggesting that the ways in which relationship quality moderates the etiology of personality may depend on the personality trait.

Screening for Intellectual Disability Using High-Resolution CMA Technology in a Retrospective Cohort from Central Brazil

PubMed Central

Pereira, Rodrigo Roncato; Pinto, Irene Plaza; Minasi, Lysa Bernardes; de Melo, Aldaires Vieira; da Cruz e Cunha, Damiana Mirian; Cruz, Alex Silva; Ribeiro, Cristiano Luiz; da Silva, Cláudio Carlos; de Melo e Silva, Daniela; da Cruz, Aparecido Divino

2014-01-01

Intellectual disability is a complex, variable, and heterogeneous disorder, representing a disabling condition diagnosed worldwide, and the etiologies are multiple and highly heterogeneous. Microscopic chromosomal abnormalities and well-characterized genetic conditions are the most common causes of intellectual disability. Chromosomal Microarray Analysis analyses have made it possible to identify putatively pathogenic copy number variation that could explain the molecular etiology of intellectual disability. The aim of the current study was to identify possible submicroscopic genomic alterations using a high-density chromosomal microarray in a retrospective cohort of patients with otherwise undiagnosable intellectual disabilities referred by doctors from the public health system in Central Brazil. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had intellectual disability and a normal karyotype. The analysis detected 18 CNVs in 60% of patients. Pathogenic CNVs represented about 22%, so it was possible to propose the etiology of intellectual disability for these patients. Likely pathogenic and unknown clinical significance CNVs represented 28% and 50%, respectively. Inherited and de novo CNVs were equally distributed. We report the nature of CNVs in patients from Central Brazil, representing a population not yet screened by microarray technologies. PMID:25061755

Renal disease in the acquired immunodeficiency syndrome in north central Nigeria.

PubMed

Agaba, E I; Agaba, P A; Sirisena, N D; Anteyi, E A; Idoko, J A

2003-01-01

The brunt of the human immunodeficiency virus infection/the acquired immunodeficiency syndrome is largely borne by communities in sub-Saharan Africa. We describe renal disease in Nigerians with the acquired immunodeficiency syndrome. Consecutive patients with the acquired immunodeficiency syndrome (AIDS) seen in the infections unit of the Jos University Teaching Hospital and a similar group of healthy controls were evaluated for renal disease. Subjects with past history of renal disease, hypovolemia, hypertension, diabetes mellitus and/or a documented fever were excluded from the study. Of the 79 patients with the acquired immunodeficiency syndrome and 57 controls studied, renal disease was present in 41 (51.8%) of the patients in the AIDS group and 7 (12.2%) of controls. While 15 (19%) of the AIDS group had azotemia alone and 20 (25.3%) had proteinuria alone, 6 (7.6%) had azotemia and proteinuria. The mean protein excretion/24 hours was significantly higher in the AIDS group compared to controls, (2.99 +/- 54 g and 0.56 +/- 0.12 g respectively, p = 0.001), while the GFR was significantly higher in controls compared to the study group (103.30 +/- 37.78 and 68.03 +/- 37.55 respectively, p = 0.004). Subjects in the AIDS group with renal disease had a significantly longer duration of illness compared to those without (12.33 +/- 8.67 months and 7.28 +/- 7.78 months respectively, p = 0.008). Age and serum CD4+ cell counts were similar in patients with and without renal disease in the AIDS group. Renal disease is a common complication of acquired immunodeficiency syndrome, the duration of illness being strongly associated with its presence.

Studies of Genetic Variation in the Aids Virus: Relevance to Disease Pathogenesis, Anti-viral Therapy, and Vaccine Development

DTIC Science & Technology

1988-03-15

variation among independent isolates of Human Immunodeficiency Virus Type 1 (HIV-1) is a widely recognized property of the virus ’- . The molecular...other lentiviral systems including eauine infectious anemia virus (EIAV), visna virus, and simian immunodeficiency virus (SIV)’ " 9. For EIAV, it is clear...tailed macaque that possesses altered biologic and antigenic properties leading to a broader host-range and a rapid, fatal immunodeficiency syndrome

Warts and All: HPV in Primary Immunodeficiencies

PubMed Central

Leiding, Jennifer W.; Holland, Steven M.

2012-01-01

Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. PMID:23036745

Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

PubMed

Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

2016-09-01

Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. Copyright © 2016 Elsevier Ltd. 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.

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, ...

Recurrent Fevers for the Pediatric Immunologist: It's Not All Immunodeficiency.

PubMed

Broderick, Lori

2016-01-01

Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation independent of infection and autoreactive antibodies or antigen-specific T cells. Similar to immunodeficiencies, these immune dysregulatory diseases have unique presentations, genetics, and available therapies. Given the presentation of fevers, rashes, and mucosal symptoms in many of the disorders, the allergist/immunologist is the appropriate medical home for these patients: to appropriately rule out immunodeficiencies, evaluate for allergic disease, and diagnose and treat recurrent fever disorders. However, many practicing physicians are unfamiliar with the clinical presentation, diagnosis, and treatment of autoinflammatory disorders. This review will focus on understanding the signs and symptoms of classic autoinflammatory disorders, introduce newly described monogenic and polygenic disorders, and address the approach to the patient with recurrent fevers to distinguish autoinflammation from immunodeficiency and autoimmunity.

ACOG Committee Opinion No. 536: Human immunodeficiency virus and acquired immunodeficiency syndrome and women of color.

PubMed

2012-09-01

In the United States, most new cases of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) occur among women of color (primarily African American and Hispanic women). Most women of color acquire the disease from heterosexual contact, often from a partner who has undisclosed risk factors for HIV infection. Safe sex practices, especially consistent condom use, must be emphasized for all women, including women of color. A combination of testing, education, and brief behavioral interventions can help reduce the rate of HIV infection and its complications among women of color. In addition,biomedical interventions such as early treatment of patients infected with HIV and pre-exposure antiretroviral prophylaxis of high-risk individuals offer promise for future reductions in infections.

Transmission of human immunodeficiency virus from parents to only one dizygotic twin.

PubMed

Park, C L; Streicher, H; Rothberg, R

1987-06-01

The acquired immunodeficiency syndrome-related complex was identified in a mother and one of her nonidentical twins. Generalized lymphadenopathy was first noted in the infant at age 17 months, and that of the mother was incidentally discovered 6 months later. The father, who had had homosexual contacts before the conception of the twins, appeared to be in good health. No one in the family had constitutional symptoms or showed signs of opportunistic infection. Both parents and the patient had hypergammaglobulinemia, low T-helper-to-suppressor-cell ratio, and positive serum antibody to human immunodeficiency virus. Attempts to isolate the virus from all family members were unsuccessful. The twin brother was in good health with a normal immunologic profile and negative antibody to human immunodeficiency virus.

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

PubMed Central

Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.

2015-01-01

IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined. PMID:25138334

Chronic Sinusitis and Risk of Head and Neck Cancer in the US Elderly Population.

PubMed

Beachler, Daniel C; Engels, Eric A

2017-01-01

Chronic sinusitis may be involved in the etiology of certain head and neck cancers (HNCs), due to immunodeficiency or inflammation. However, the risk of specific HNCs among people with chronic sinusitis is largely unknown. To evaluate the associations of chronic sinusitis with subsequent HNC, including nasopharyngeal cancer (NPC), human papillomavirus-related oropharyngeal cancer (HPV-OPC), and nasal cavity and paranasal sinus cancer (NCPSC), in an elderly US population. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to conduct a case-cohort study of US individuals aged 65 years or older during 2004 through 2011. The study included 483 546 Medicare beneficiaries from SEER areas in a 5% random subcohort, and 826 436 from the entire source population who developed cancer (including 21 716 with HNC). Incidence of HNCs including NPC, HPV-OPC, and NCPSC. Most individuals were female (57.7%), and the mean (SD) age at entry was 72.6 (8.0) years. Chronic sinusitis was associated with risk of developing HNC (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.27-1.48), particularly NPC (aHR, 3.71; 95% CI, 2.75-5.02), HPV-OPC (aHR, 1.33; 95% CI, 1.13-1.57), and NCPSC (aHR, 5.49; 95% CI, 4.56-6.62). Most of this increased risk was limited to risk within 1 year of the chronic sinusitis diagnosis, as associations were largely attenuated 1 year or more after chronic sinusitis (NPC: aHR, 1.60; 95% CI, 0.96-2.65; HPV-OPC: aHR, 1.07; 95% CI, 0.86-1.32; NCPSC: aHR, 2.47; 95% CI, 1.84-3.31). All 3 HNC subtypes had cumulative incidence of less than 0.07% 8 years after chronic sinusitis diagnosis. Chronic sinusitis is associated with certain HNCs, particularly NPC and NCPSC. These HNCs are rare, and most of the increased HNC risk is limited to within 1 year of chronic sinusitis diagnosis, consistent with surveillance or detection bias. The associations were weaker over longer intervals, suggesting at most a modest role for sinusitis-related inflammation and/or immunodeficiency.

HIV/AIDS-Related Attitudes and Practices Among Traditional Healers in Zambézia Province, Mozambique

PubMed Central

Blevins, Meridith; Moon, Troy D.; Sidat, Mohsin; Shepherd, Bryan E.; Pires, Paulo; Vergara, Alfredo; Vermund, Sten H.

2012-01-01

Abstract Objectives To document HIV knowledge, treatment practices, and the willingness of traditional healers to engage with the health system in Zambézia Province, Mozambique. Settings/location Traditional healers offer culturally acceptable services and are more numerous in Mozambique than are allopathic providers. Late presentation of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) is reported among persons who have first sought care from traditional healers. Design One hundred and thirty-nine (139) traditional healers were interviewed in their native languages (Chuabo or Lomwe) in Zambézia Province. Furthermore, 24 traditional healers were observed during patient encounters. Healers answered a semistructured questionnaire regarding their knowledge of HIV/AIDS, general treatment practices, attitudes toward the allopathic health system, and their beliefs in their abilities to cure AIDS. Results Traditional healers were older and had less formal education than the general population. Razor cutting in order to rub herbs into bloodied skin was observed, and healers reported razor cutting as a routine practice. Healers stated that they did not refer HIV patients to clinics for two principal reasons: (1) patient symptoms/signs of HIV were unrecognized, and (2) practitioners believed they could treat the illness effectively themselves. Traditional healers were far more likely to believe in a spiritual than an infectious origin of HIV disease. Prior HIV/AIDS training was not associated with better knowledge or referral practices, though 81% of healers were interested in engaging allopathic providers. Conclusions It was found that the HIV-related practices of traditional healers probably increase risk for both HIV-infected and uninfected persons through delayed care and reuse of razors. Mozambican traditional healers attribute HIV pathogenesis to spiritual, not infectious, etiologies. Healers who had received prior HIV training were no more knowledgeable, nor did they have better practices. The willingness expressed by 4 in 5 healers to engage local formal health providers in HIV/AIDS care suggests a productive way forward, though educational efforts must be effective and income concerns considered. PMID:23171035

Studies of Genetic Variation in the AIDS Virus: Relevance to Disease Pathogenesis, Anti-Viral Therapy, and Vaccine Development

DTIC Science & Technology

1990-06-15

lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868-870. 4. Berkelman, R.L., W.L. Heyward...J.K. Stehr-Green and J.W. Curran. 1989. Epidemiology of human immunodeficiency virus infection and acquired immunodeficiency syndrome . Amer. J. of Med...cytopathicity. In: Acquired Immunodeficiency Syndrome . Eds. J.C. Gluckman and E. Vilmer. (Elsevier) pp. 47- 56. 26. Henderson, L.E., R.C. Sowder, T.D

Progressive multifocal leukoence--phalopathy presenting as homonymous hemianopia in a patient with acquired immunodeficiency syndrome.

PubMed

Pandey, Amit; Bandivdekar, Karishma; Ramchandani, Suresh; Ramchandani, Sushama

2012-01-01

We present a case of a Human Immunodeficiency Virus (HIV) positive patient who was referred for retinal evaluation to rule out ophthalmic manifestations of Acquired Immunodeficiency Syndrome (AIDS). She complained of some disturbance in vision in both eyes. Fundus examination showed no abnormality. Perimetry, done to rule out optic nerve pathology, showed a left homonymous hemianopia. Magnetic Resonance Imaging (MRI) scan showed features of Progressive Multifocal Leukoencephalopathy (PML). She had no other neurological symptoms or signs.

Perforating neutrophilic and granulomatous dermatitis of the newborn--a clue to immunodeficiency.

PubMed

Torrelo, Antonio; Vera, Angel; Portugués, Mar; de Prada, Inmaculada; Sanz, Andrés; Colmenero, Isabel; Zulaica, Ander; de Lucas, Raúl; Fraga, Javier; Pedraz, Javier; Fontán, Sindo; Zambrano, Antonio

2007-01-01

We report two newborns with a widespread cutaneous eruption consisting of discrete papules which evolved into vesicles, pustules, crusts, and ulcers. These healed over a 2-week period with scarring. Histopathology showed three main features--histiocytic granulomas, neutrophilic infiltration, and transepidermal elimination of degenerated collagen and debris through hair follicles. Both patients had congenital immunodeficiency. This skin condition of the newborn, with distinct clinical and histopathologic features, is a manifestation of immunodeficiency that has not been previously described.

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

State policies and the financing of acquired immunodeficiency syndrome care

PubMed Central

Pascal, Anthony; Cvitanic, Marilyn; Bennett, Charles; Gorman, Michael; Serrato, Carl A.

1989-01-01

State policies, with respect to the operation of Medicaid programs and the regulation of private health insurance, affect who gets what care, how much is spent, and who ultimately pays. A RAND Corporation study was used to assess States and the District of Columbia in terms of the effects of their Medicaid and health insurance regulations on people with acquired immunodeficiency syndrome and other human immunodeficiency virus-related illnesses. State characteristics are used to explain the individual State policy rankings. PMID:10313357

Portrait of an Epidemic: Extremely High Human Immunodeficiency Virus Prevalence and Incidence Among Young Black Men Having Sex With Men and Residing in a Southern City.

PubMed

Mena, Leandro; Crosby, Richard A

2017-07-01

A 12-month prospective cohort study of 609 young black men who have sex with men (YBMSM) assessed human immunodeficiency virus seroconversion. One-hundred-seventy men (27.9%) were either human immunodeficiency virus-infected before enrollment or tested positive within 30 days afterward. Thirty (4.9%) were classified as incident infections occurring in a 12-month period. Subtracting the 170 from the denominator, incidence was 6.8%.

Continuous relative phase variability during an exhaustive run in runners with a history of iliotibial band syndrome.

PubMed

Miller, Ross H; Meardon, Stacey A; Derrick, Timothy R; Gillette, Jason C

2008-08-01

Previous research has proposed that a lack of variability in lower extremity coupling during running is associated with pathology. The purpose of the study was to evaluate lower extremity coupling variability in runners with and without a history of iliotibial band syndrome (ITBS) during an exhaustive run. Sixteen runners ran to voluntary exhaustion on a motorized treadmill while a motion capture system recorded reflective marker locations. Eight runners had a history of ITBS. At the start and end of the run, continuous relative phase (CRP) angles and CRP variability between strides were calculated for key lower extremity kinematic couplings. The ITBS runners demonstrated less CRP variability than controls in several couplings between segments that have been associated with knee pain and ITBS symptoms, including tibia rotation-rearfoot motion and rearfoot motion-thigh ad/abduction, but more variability in knee flexion/extension-foot ad/abduction. The ITBS runners also demonstrated low variability at heel strike in coupling between rearfoot motion-tibia rotation. The results suggest that runners prone to ITBS use abnormal segmental coordination patterns, particular in couplings involving thigh ad/abduction and tibia internal/external rotation. Implications for variability in injury etiology are suggested.

Motion Cues in Flight Simulation and Simulator Induced Sickness

DTIC Science & Technology

1988-06-01

asseusod in a driving simulator by means of a response surface methodology central-composite design . The most salient finding of the study was that visual...across treatment conditions. For an orthogonal response surface methodology (IBM) design with only tro independent variables. it can be readily shown that...J.E.Fowikes 8 SESSION III - ETIOLOGICAL FACTORS IN SIMULATOR-INDUCED AFTER EFFETS THE USE OF VE& IIBULAR MODELS FOR DESIGN AND EVALUATION OF FLIGHT

A Comparative Analysis of the Murine Thymic Microenvironment in Normal, Autoimmune, and Immunodeficiency States

PubMed Central

Takeoka, Yuichi; Chen, Shao-Yuan; Boyd, Richard L.; Tsuneyama, Koichi; Taguchi, Nobuhisa; Morita, Shinji; Yago, Hisashi; Suehiro, Seishi; Ansari, Aftab A.; Shultz, Leonard D.

1997-01-01

It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this is that abnormalities within the microenvironment could be of etiologic significance in T-cell-based diseases. Our laboratory has developed a large panel of monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial markers in the thymus. We have taken advantage of these reagents to characterize the thymic microenvironment of several genetic strains of mice, including BALB/cJ, C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcph me/Hcph me, and ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control mice, including strains of several backgrounds, have a very consistent phenotypic profile with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix. In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex and medulla at both the structural and cellular levels. These phenotypic data suggest that abnormalities in interactions between developing thymocytes and stromal cells characterize disease-prone mice. PMID:9587708

Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease.

PubMed Central

Urnovitz, H B; Murphy, W H

1996-01-01

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated. PMID:8665478

Pediatric allergy and immunology in Brazil.

PubMed

Rosario-Filho, Nelson A; Jacob, Cristina M; Sole, Dirceu; Condino-Neto, Antonio; Arruda, Luisa K; Costa-Carvalho, Beatriz; Cocco, Renata R; Camelo-Nunes, Inês; Chong-Neto, Herberto J; Wandalsen, Gustavo F; Castro, Ana P M; Yang, Ariana C; Pastorino, Antonio C; Sarinho, Emanuel S

2013-06-01

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.