Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.
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PMID:Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients. 216 65

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

Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has rarely been reported. We present a retrospective cohort study of 1825 HIV-positive patients seen at one inner London HIV clinic over a two-year period. In all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy. Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy, haematological malignancy). Of the remaining 11 patients, two were on no medication and eight (73%) were receiving ritonavir as a boosted protease inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the 18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was seen in patients with known risk factors for gout or who were receiving ritonavir as a boosted PI and who also had lipodystrophy.
Int J STD AIDS 2005 May
PMID:Is ritonavir boosting associated with gout? 1594 66

Critical to the discovery and development of drugs and vaccines is the rational selection of biochemical, immunologic or molecular targets. To understand the rationale for target selection, we review strengths and weaknesses of the four main approaches: whole animal disease models; molecular targeting; epidemiology/observation studies, and genomics. After classifying diseases into those with a relatively stable pathophysiology (e.g., hypertension and gout) versus those with an unstable pathophysiology (e.g., AIDS and influenza) to aid in understanding target selection, we provide examples of successful and unsuccessful selection of drug and vaccine targets, focusing on the molecular and epidemiological/observational approaches. We discuss the reasons that molecular targeting has led to successful control of many diseases, whereas the epidemiological/observational approach has had a checkered history. We also assess the potential power of the genomic approach, specifically the curative versus controlling/preventive strategies. With combined genetic and molecular approaches and judicious use of whole animal models and properly performed epidemiology/observation studies to select the appropriate targets, the future for controlling, preventing and even curing many diseases is very bright indeed.
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PMID:The heart of drug discovery and development: rational target selection. 1667 15

The authors report 100 cases of knee septic arthritis seen during ten years among 2298 patients admitted in the rheumatology department of Brazzaville university teaching hospital. Bone and joint infection is the first hospitalisation cause in this service. Knee is the first septic localization with 42% of cases coming before hip 25%, sacro-iliac 18% and shoulder 7%. Patients are 56 males and 44 females aged from 5 to 79 years old, average 35 years. Most frequently germs are Staphylococcus aureus in half cases, Mycobacterium tuberculosis in 30% of cases and gram-negative bacillus. Contributing factors are AIDS: 12 cases, diabetes mellitus: 7 cases, alcohol-tobacco intoxications: 4 cases, ickle-cell disease: 3 cases, gout and renal failure in 2 cases each. Late diagnosis and consultation, inadapted antibiotic drugs are responsible for important articular damages compromising further functional prognosis.
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PMID:[Knee septic arthritis: 100 cases report in intertropical zone]. 1730 42

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol.
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PMID:Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity. 2150 Nov 18

A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson's and Alzheimer's diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007-2017) on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.
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PMID:Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications. 2931 46

Gout is the most common inflammatory arthritis worldwide. Its principal risk factor is hyperuricaemia. While gout has been described in HIV patients and numerous more outdated anti-retroviral therapies (ARTs) have been implicated, there have been few recent studies. Our case-control study investigated the prevalence of and risk factors for gout in an established HIV cohort. Cases were identified from database searches using key search terms, with two age- and gender-matched controls. These were compared for demographic factors, co-morbidities, HIV factors and ART exposure. Forty-five cases with gout were identified (point prevalence 2.2%). All were male and were more likely than controls to be of black African origin. Hypertension was associated with an almost five-fold increased gout risk (OR 4.8, 95% CI 1.8-12.4). No individual drug or ART class was associated with gout in this study but exposure to non-nucleoside reverse transcriptase inhibitors had a significantly protective effect against the risk of gout (OR 0.3, 95% CI 0.1-0.9). Our data suggest that gout is common in HIV patients and that the traditional risk factors, especially hypertension, play a key role. Gout and hyperuricaemia should be regarded as a biomarker of cardiovascular disease in HIV patients as they are in the general population.
Int J STD AIDS 2019 03
PMID:Prevalence of and risk factors for gout in HIV-positive adults: A case-control study. 3039 64