Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations in body shape due to fat loss and/or redistribution have been described in HIV-infected individuals and associated with the use of antiretroviral (ARV) combination therapy. Certain of these changes have been referred to as peripheral lipodystrophy (LD) and we describe 12 patients who were recognized with this condition between September 1997 and February 1998. It occurred in 12.5% of patients on ARV combination therapy that included a protease inhibitor (PI). In early descriptions the emphasis was on the abdomen, which may be grossly enlarged. In our patients this feature was much less marked. Patients with LD were significantly older than those on PI therapy who did not develop this condition (P=0.016). Although all had raised triglyceride (TG) levels, the elevations were not severe (maximum=6.3 mmol/l). CD4 lymphocyte and viral load levels suggested an optimal response to ARV therapy at the time LD developed. Appearances may be disfiguring but no serious systemic consequences of LD have been observed. Most individuals have chosen to remain on their present ARV combinations. When LD occurs, it appears to be a marker of effective response to anti-HIV therapy.
Int J STD AIDS 1998 Oct
PMID:Disorders of fat distribution in HIV infection. 981 10

The past decade has seen great advances in the management of patients with HIV infection. The introduction of highly active antiretroviral therapy (HAART) has resulted in a decrease in opportunistic infections but the development of new clinical entities such as lipodystrophy and immune reconstitution illnesses. The use of investigations such as lipid profiles and dual energy X-ray absorptiometry (DEXA) scanning to assess lipodystrophy have been necessitated by these changes in the epidemic. Technological advances have resulted in new techniques such as viral resistance assays and single photon emission computed tomography (SPECT) scanning. The appropriate use of these investigations is subject to ongoing assessment.
Int J STD AIDS 2001 Jan
PMID:The investigation of patients with HIV infection: 10 years of progress. 1156 38

The 12th World AIDS Conference in Geneva provided evidence that STD prophylaxis/treatment does not reduce HIV transmission. New guidelines for antiretroviral therapy in terms of when to treat and when to change are also presented. Research findings and practical applications are also provided for the following areas: HIV therapeutic monitoring, immune reconstitution, prevention, TMP-SMX prophylaxis, lipodystrophy, serum lipid changes, and diabetes.
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PMID:Conference news at a glance. 1136 77

We report a case of gynaecomastia developed in a HIV-seropositive man, associated with a severe lipodystrophy. We hypothesize the responsibility of stavudine and didanosine in the development of these 2 complications. If many reports suggest that the protease inhibitors may promote gynaecomastia, long-term nucleoside analogue therapy may also cause this side effect.
Int J STD AIDS 2001 Jul
PMID:Gynaecomastia in a male patient during stavudine and didanosine treatment for HIV infection. 1139 87

Healthcare workers (HCWs) worldwide risk occupational exposure to HIV and other blood-borne pathogens. Post-exposure prophylaxis (PEP) may decrease the risk of seroconversion after occupational or sexual exposure. Current guidelines recommend immediate PEP with at least 2 drugs following HIV exposure. In high-risk exposures, the guidelines recommend the use of a protease inhibitor (PI) as well as 2 reverse transcriptase inhibitors. Protease inhibitors have been associated with dyslipidaemias, other metabolic abnormalities and lipodystrophy syndromes in AIDS patients. We report a case of new transient lipid abnormalities in a HCW receiving PEP after HIV exposure. HIV medications may produce occult metabolic abnormalities in HIV-negative individuals receiving PEP. This risk should be considered during follow-up evaluation for PEP.
Int J STD AIDS 2001 Aug
PMID:Lipid abnormalities in a healthcare worker receiving HIV prophylaxis. 1148 94

The CBP protein (cAMP response element binding protein (CREB) binding protein) is a co-activator for several transcription factors with a wide range of important biological functions, such as sterol regulatory element binding proteins (SREBPs), CCAAT/enhancer-binding proteins (C/EBPs), nuclear receptors (including peroxisome proliferator-activated receptors, PPARs), and signal transducers and activators of transcription (STATs). In contrast to these individual transcription factors, the biological roles of CBP are poorly understood. CBP enhances transcriptional activities via histone acetylation and the recruitment of additional co-activators such as SRC (steroid coactivator)-1 (ref. 9). To identify its physiological functions using a loss-of-function mutant, we analyzed CBP-deficient mice. As Crebbp null mice (Crebbp-/-) died during embryogenesis, we used Crebbp+/- mice. Unexpectedly, Crebbp+/- mice showed markedly reduced weight of white adipose tissue (WAT) but not of other tissues. Despite this lipodystrophy, Crebbp+/- mice showed increased insulin sensitivity and glucose tolerance and were completely protected from body weight gain induced by a high-fat (HF) diet. We observed increased leptin sensitivity and increased serum adiponectin levels in Crebbp+/- mice. These increased effects of insulin-sensitizing hormones secreted from WAT may explain, at least in part, the phenotypes of Crebbp+/- mice. This study demonstrates that CBP may function as a 'master-switch' between energy storage and expenditure.
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PMID:Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. 1181 64

This study was a cross-sectional study of 122 HIV-positive subjects to determine the prevalence and predictors of weight loss in the era of highly active antiretroviral therapy (HAART). Forty per cent reported lipodystrophy, 40% had documented weight loss (mean 6.6 kg). Mean intake 13,400 kJ (118% of estimated requirements calculated using the Harris-Benedict equation). One hundred (82%) were taking antiretroviral therapy. Using forward stepwise logistic regression analysis only viral load (VL) was significantly associated with weight loss when intake, CD4 T-cell count, lipodystrophy, and age were entered into the model with VL (log copies/mL). Every one log increase in HIV VL was associated with an odds of weight loss of 1.58 (P=0.0008). Weight loss is still common in the HAART era. HIV VL was the most significant predictor of weight loss in this sample. Inadequate dietary intake and self-reported lipodystrophy were not related to weight loss in this population.
Int J STD AIDS 2002 Nov
PMID:Prevalence and predictors of HIV-associated weight loss in the era of highly active antiretroviral therapy. 1243 93

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.
Int J STD AIDS 2004 Apr
PMID:Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan. 1507 19

Our objective is to analyse patients diagnosed with late-stage HIV infection in the highly active antiretroviral therapy (HAART) area. A prospective, observational study of all patients with an initial CD4 < 50 x 10(6)/L was carried out. Epidemiological, clinical and HAART-associated data were analysed. Survival rates were estimated and pairs of survival curves were compared. The statistical program used was SPSS (version 10). In all, 349 HIV-infected patients were diagnosed, 117 (33.5%) had late-stage disease, mean CD4 23.9 x 10(6)/L and mean viral load (VL) 5.38 log10. In 98 men, mean age 39.5 years, percentage of AIDS cases at their first attendance was 83.8%. The median follow-up period was 28 months and 27 died. Pneumocystis carinii was the most frequent cause of AIDS (24.4%) and death (18.5%). Survival rates at 12, 24 and 36 months were 95.6%, 85.8% and 72.4%. HAART was started in 82.1%. VLs < 50 copies/mL at one, two and three years of treatment were 55.2%, 55.7% and 58.0%. Resource utilization included 0.58 hospitalization/patient/year and 0.07 events/patient/year. HAART-related complications were as follows: 50% lipodystrophy, 9.7% hypertension, 22.2% hyperglycaemia, 26.4% hypercholesterolaemia, 31.9% hypertrygliceridaemia and 18.1% mixed hyperlipaemia. Over one-third of our patients have advanced HIV infection at diagnosis. However, the outcome is favourable, with a good immunovirological response and few new opportunistic events. HAART-related complications were frequent.
Int J STD AIDS 2005 Mar
PMID:Study of patients diagnosed with advanced HIV in the HAART era--OMEGA Cohort. 1582 28

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


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