Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been an explosion of knowledge in disorders of purine and pyrimidine metabolism during the last 20 years. During this time, more than 10 diseases have been discovered and their metabolic bases studied. Hyperuricemia and gout remain the most common clinical disorder. Rarely these disorders are explainable by an inherited enzyme abnormally, such as hypoxanthine-guanine phosphoribosyltransferase deficiency, phosphoribosyl-pyrophosphate synthetase deficiency, or glucose-6-phosphatase deficiency. The description of immunodeficiency syndromes in association with purine enzyme deficiency has led to a novel area of investigation encompassing the biochemical basis for immune function. Although less information is available concerning the other diseases associated with renal calculi, myopathy, anemia, and central nervous system dysfunction, further research will elucidate important metabolic relationships. These will no doubt expand our understanding of the pathogenesis of these disorders and provide innovative therapeutic approaches.
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PMID:Disorders associated with purine and pyrimidine metabolism. 609 39

Contrary to previous belief, there is increasing evidence that a broad spectrum of rheumatic diseases do affect African blacks. Although properly conducted epidemiological studies have yet to be performed, reports of population surveys from a variety of sub-Saharan African countries indicate that diseases such as rheumatoid arthritis (RA), gout, and the connective tissue diseases are observed, although some differences in clinical presentation may occur as a result of cultural, racial, and socioeconomic factors. Rheumatoid arthritis is common in some parts of Africa and less common in others. In particular, a significantly lower prevalence of RA in rural areas compared with urban cohorts has led to the hypothesis that environmental factors associated with urbanization may be involved in disease pathogenesis. A similar hypothesis has been suggested for hyperuricemia and gout. Clinical features of disease may also be different in Africans when compared with other population subgroups such as with systemic lupus erythematosus although this may be artefactual as different accessibility to health care and referral practices may result in only the more severe cases coming to medical attention (eg, lupus nephritis). Immunogenetic factors may reduce the prevalence of some conditions such as the spondyloarthropathies. Although the association between HLA-DR4 and RA holds true in Africans, the same is not so for the association of HLA-B27 with ankylosing spondylitis (AS). The prevalence of HLA-B27 in African blacks is 10 times less than Caucasian populations, in part accounting for the low prevalence of spondyloarthropathies, although its association with AS is low. Other conditions such as human immunodeficiency virus (HIV)-related arthropathies appear to be an increasing medical problem. The panepidemic of acquired immunodeficiency syndrome in Africa has resulted in an increased awareness of the different types of arthritis that may be associated with HIV. These are similar to those reported in other parts of the world, although risk factors are different in Africa where heterosexual transmission is a more common cause than homosexual transmission or i.v. drug usage. Information on other rheumatic diseases such as osteoarthritis and soft tissue rheumatism are slowly emerging. Rheumatic manifestations of the infectious diseases, which are endemic in Africa, remain a uniquely fascinating aspect of rheumatology practice on the African continent. Therefore, African countries will increasingly be a continued valuable source of clinical material for comparative studies to help elucidate factors that influence the development of rheumatic diseases.
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PMID:Rheumatic diseases in African blacks. 783 55

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.
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PMID:Challenges in the management of Burkitt's lymphoma. 1252 85

Delusional parasitosis (DP) is a psychotic condition in which a person has the unshakeable and mistaken belief (delusion) and/or aberrant perception (hallucination) of being infested with parasites. The disorder will be usually classified in a primary DP-group without a detectable cause (so-called pure forms), while secondary DP-groups are associated with general organic conditions, psychiatric illnesses and drugs (substance induced). Etiology and pathophysiology of DP remain however unknown. In the present paper we hypothesize for the first time a decreased striatal dopamine transporter (DAT)-functioning (corresponding with an increased extracellular dopamine-level) as etiologic condition for DP (primary and secondary groups). The DAT as key regulator of the dopamine-reuptake in the human brain is well known (regulation of the extracellular dopamine concentration). It is a presynaptic plasma membrane protein highly dense represented in the striatum. The hypothesis of a decreased DAT-functioning as etiologic condition by DP is revealed in case reports which show that DAT-inhibitors, such as cocaine, pemoline, methylphenidate and other amphetamine-derivatives can induce the clinical expression of DP. Several other associated causes of secondary DP-groups (medications, parkinson, chorea huntington, multiple system atrophy, diabetes, cerebrovascular diseases, alcoholism, traumatic brain injury, hyperuricemia, human immunodeficiency virus, iron deficiency, schizophrenia, depression) suggest that the clinical expression of DP may be related to a decreased striatal DAT-functioning (blocking, reduced ligand binding, reduced density, reduced activity). Our examined DP-cases (2-females) show means of magnetic resonance imaging a structurally damaged striatum. Furthermore, we presume that by the primary DP-group, the physiologically age-related decline of the DAT-density is pathologically elevated. Based on this hypothesis we show in the present paper the relation between DP and decreased striatal DAT-functioning, trying to give a new insight into the pathophysiologically mechanism involved. The hypothesis provides supporting evidence that increased levels of extracellular dopamine in the striatum of DP-patients is likely to be the result of decreased DAT-functioning and not increased rates of release. The hypothesis can be investigated simply by dopamine transporter imaging in patients with DP.
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PMID:Delusional parasitosis and the dopamine transporter. A new insight of etiology? 1713 47

Metabolic syndrome (MetS) is a cluster of risk factors, including elevated mean arterial pressure (MAP), atherogenic dyslipidemia (elevated triglycerides [TRG]), abdominal obesity (increased body mass index [BMI]), glucose intolerance (elevated glucose [GLU]), and prothrombotic/inflammatory state (increases in uric acid [UA]), that are associated with increased risk of cerebrovascular disease. We studied if an association existed between MetS components and human immunodeficiency virus (HIV)-associated cryptogenic strokes-those not caused by HIV complications, endocarditis, or stimulant abuse. We performed a retrospective case-control study. Eleven cryptogenic strokes were identified from 2346 HIV-infected (HIV+) participants. Each case was matched by age, sex, and date of stroke diagnosis to five HIV+ controls without stroke. Nonparametric stratified Wilcoxon ranked sum tests with subsequent mixed effect logistic regression determined the influence of each MetS component on HIV-associated cryptogenic stroke. Although each MetS component appeared higher for HIV+ cases with cryptogenic strokes than HIV+ controls, only MAP (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 1.15-28.3) and UA (OR = 1.88, 95% CI = 1.06-3.32) were statistically different. A significantly higher percentage of HIV-associated cryptogenic stroke cases met criteria for MetS (4/11 = 36%) compared to HIV+ controls (6/55 = 11%). This observational study suggests a possible role for MetS components in HIV+ cryptogenic stroke cases. Although MetS is defined as a constellation of disorders, elevated hypertension and hyperuricemia may be involved in stroke pathogenesis. Reducing MetS component levels in HIV+ patients could therefore protect them from subsequent stroke.
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PMID:Role of metabolic syndrome components in human immunodeficiency virus-associated stroke. 1956 11

Purines and pyrimidines, regarded for a long time merely as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, have attracted increasing attention after genetically determined aberrations in their metabolism were linked to a range of symptoms from hyperuricemia and immunodeficiency to neurological disorders. The pathogenesis of such disorders involves cell or mitochondrial damage, but the molecular mechanisms underlying symptoms is often unclear. H. Anne Simmonds made major contributions to the metabolic, clinical, and molecular aspects of these disorders and the Purine Research Laboratory, which she established in London, became the world center for clinical and experimental studies in the field. We owe her gratitude not only for this direct contribution but also for her enthusiasm for purine and pyrimidine research that she transmitted to generations of scientists. Our research in this field stemmed from expertise in pyridine metabolism and its connection with purines, and from clinical involvement with biochemical diagnosis of enzyme deficiencies. We joined H. Anne Simmonds in studying the biochemical basis of altered NAD content in erythrocytes of PNP- and HPRT-deficient patients, discovering some alterations in NAD synthesis and breakdown.
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PMID:Inborn errors of purine and pyrimidine metabolism: how much we owe to H. Anne Simmonds. 2213 80

On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised Response Criteria for Malignant Lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (P = 0.0012). The most common adverse reactions (>10% compared with placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.
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PMID:FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. 2647 94

Introduction: Drug-drug interactions (DDI) between antiretroviral drugs and drugs for the treatment of metabolic disturbances in people living with human immunodeficiency virus (HIV) (PLWH) have represented a problem of paramount importance in the recent times. The problem has been mainly driven by sharing common metabolizing pathways. This problem has classically been worsened by the frequent use of pharmacokinetic boosters to enhance protease inhibitors and some integrase inhibitors plasma levels. Areas covered: This article focuses on the interactions between antiretroviral drugs and those drugs used to treat metabolic disturbances which frequently appear in PLWH. These include dyslipidemia, diabetes mellitus, hyperuricemia, and finally, drugs for the treatment of overweight and clinical obesity. References from PubMed, Embase, or Web of Science, among others, were reviewed. Expert opinion: The advent of safer drugs, in terms of DDI, in the antiretroviral and the metabolic field,such as non-boosted antiretrovirals and drugs with divergent metabolizing paths. Besides, learning by the caregivers on how to decrease and manage DDI, together with the extensive use of online updated DDI databases, has undoubtedly minimized the problem. The foreseeable increase in the burden of HIV-associated comorbidities and their associated treatments anticipates further complexities in the management of DDI in PLWH.
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PMID:Drug-drug interactions when treating HIV-related metabolic disorders. 3151 29