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)

Two appetite stimulants, megestrol acetate and cyproheptadine were administered in a randomized trial to 14 patients who had no evidence of opportunistic infection or malabsorption but were wasted (had lost more than 5 kg body weight) as a result of human immunodeficiency virus (HIV) infection. Energy intakes were calculated from a 7 day weighed dietary record. Mean energy intakes per kilogramme body weight were similar in both treatment groups (greater than 34 kcal/kg) and were higher than that in well British males. Energy intakes increased by just over 500 kcal during both treatments, but fell to pretreatment levels after therapy. Patients in both treatment groups gained a moderate amount of weight. Megestrol acetate was associated with impotence in 4 patients. Insufficient calorie intake alone is not a common cause of wasting associated with HIV and the role of appetite stimulants is likely to be limited.
Int J STD AIDS
PMID:Megestrol acetate vs cyproheptadine in the treatment of weight loss associated with HIV infection. 150 60

We examined all reports of adult AIDS cases made to the 2 national surveillance centres in the UK for changes in AIDS defining conditions between January 1982 and September 1994. Differences and changes among persons diagnosed since January 1988 who had and had not been aware of their HIV infection prior to their AIDS diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is the AIDS defining disease most often reported at the initial AIDS diagnosis. Its proportion of all AIDS cases has increased significantly between January 1982 and December 1987 and decreased markedly thereafter. Since January 1988 a significant decrease in the proportion of cases diagnosed with cryptosporidial infection was also observed while increases were observed in the proportion of cases diagnosed with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For cases diagnosed between January 1988 and September 1994, PCP was more likely to be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more likely to be diagnosed in patients already aware of their HIV infection prior to the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P = 0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P < 0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02). Prophylaxis and anti-retroviral therapy appear to have had a significant impact on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS, the corresponding increase in other opportunistic infections suggests that there may be a need for improved prophylaxis for these conditions.
Int J STD AIDS 1996 Jul
PMID:AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years of change. 887 55

The use of testosterone to treat clinical symptoms of hypogonadism and wasting among patients with HIV/AIDS is a relatively new area of inquiry and clinical application. Outcome measures have included changes in mood, libido, energy, weight and muscle mass. The purpose of this review is to identify the questions most commonly raised about risks of testosterone therapy, to review available data which address these questions, and to discuss issues of clinical management. These include treatment indications, measurement issues, and side effects and their management.
Int J STD AIDS 1997 Sep
PMID:Testosterone treatment of clinical hypogonadism in patients with HIV/AIDS. 929 41

Findings are presented from a cross-sectional study conducted in 1995 in Bobo-Dioulasso, Burkina Faso, in which the patterns of diseases and CD4 counts among 266 HIV-infected adults of mean age 33 years were analyzed. The bioclinical spectrum of subjects' HIV disease is described and a simple alternative proposed to CD4 enumeration for screening and monitoring HIV-infected Africans. Dermatological symptoms and diarrhea were the most frequent signs associated with B-stage disease, while cachexia and digestive candidosis were the most frequent AIDS-defining diseases (ADD). Peripheral facial paralysis and cutaneo-mucous diseases were associated with weak immune deficiency. Pulmonary tuberculosis (TB) was close to B-stage diseases, and chronic diarrhea was borderline between B and C stages. Cachexia was the most frequent C-stage symptom (47.8%). 90% of CDC C-stage subjects had CD4 counts of less than 350 per mcl, while only 75% had CD4 counts under 200/mcl. Regression analysis identified the lymphocyte count, clinical stage, and platelet count as predictors of CD4 count below 350/mcl. A lymphocyte count of less than or equal to 2500/mcl and clinical stage of B or higher is proposed to determine the CD4 threshold and to determine those patients in need of treatment to prevent wasting and opportunistic infections.
Int J STD AIDS 1998 Aug
PMID:A proposal for basic management of HIV disease in west Africa: use of clinical staging and haemogram data. 970 95

The long-term effects of fat metabolism, storage and utilization in HIV-1 infected patients on highly active antiretroviral therapy (HAART) including a protease inhibitor are profound and cause increasing concern. The main importance of these lipid/metabolic disorders lies in their assumed contribution to an increased risk of coronary heart disease (CHD). In the general population increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor for CHD by itself as well as in combination with increased levels of cholesterol and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1 positive patients were screened for cardiovascular risk factors. The subjective perception of fat wasting and/or accumulation in different sites of the body, which was possible to evaluate in 235 patients on HAART and 73 treatment-naive patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high-density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of the patients on HAART, 42% (98/235) reported abnormal fat distribution as compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a) levels (> 700 mg/l) were more common among HAART patients as compared with naive, 14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not differ between patients with and without subjective perception of abnormal fat distribution. A significant number of the HAART patients had very high levels of Lp(a) and various combinations of increased lipid values associated with considerably increased risk for CHD. The elevation of Lp(a) did not relate to any other clinical or laboratory parameter than to LDL-cholesterol.
Int J STD AIDS 2000 Jul
PMID:Serum lipid levels associated with increased risk for cardiovascular disease is associated with highly active antiretroviral therapy (HAART) in HIV-1 infection. 1091 87

This retrospective study of risk factors for testicular atrophy in HIV-infected men investigates the relationship between complications of AIDS such as wasting or opportunistic illness and testicular atrophy. Microscopic sections of the right testis were evaluated for testicular atrophy by assessing the mean score in each of 80 selected HIV-infected patients who underwent an autopsy during a one-year period. A significant association was observed between testicular atrophy and body mass index (BMI) (P=0.0496). Thus, underweight patients with HIV infection were 3.52 times more likely to have testicular atrophy than those with acceptable body weight. Other significant associations between other variables were not found.
Int J STD AIDS 2001 Apr
PMID:Testicular atrophy in 80 HIV-positive patients: a multivariate statistical analysis. 1131 71

Switch studies have been carried out to explore changes in side effects in adherence. Discontinuing the protease inhibitor (PI) component of highly active antiretroviral therapy (HAART) regimen is often associated with improved adherence and improved quality of life. Following switching from a PI to a non-nucleoside reverse transcriptase inhibitor or abacavir, there is however a clear trend toward an improved metabolic profile particularly in insulin resistance and triglyceride levels when patients discontinue their PI. Peripheral wasting is likely to be associated with nucleoside analogues and for individuals with isolated fat accumulation, modification of HAART is not recommended. Virological suppression can be maintained following switch if adequate suppression of the virus has been achieved for at least six months prior to switch and the patient has not been previously exposed to suboptimal HAART. Discontinuing the PI preserves this class of agents for future use. Switching however may be associated with other side effects; hypersensitivity, skin rashes, hepatic or neuropsychiatric events.
Int J STD AIDS 2003 Sep
PMID:Perspectives on HAART: switch maintenance therapy. 1451 91

Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12+1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m(2)/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin-angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin-angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria.
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PMID:Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. 1651 45

Growth hormone (GH) is a major regulatory factor for overall body growth as evidenced by the height extremes in people with abnormal circulating GH levels or GH receptor (GHR) disruptions. GH also affects metabolism, cardiac and immune function, mental agility and aging. Currently, GH is being used therapeutically for a variety of clinical conditions including promotion of growth in short statured children, treatment of adults with GH deficiency and HIV-associated wasting. To help reveal previous unrecognized functions of GH, better understand the known functions of GH, and avoid adverse consequences that are often associated with exogenous GH administration, careful delineation of the molecular mechanisms whereby GH induces its diverse effects is needed. GH is a peptide hormone that is secreted into the circulation by the anterior pituitary and acts upon various target tissues expressing GHR. GH binding of GHR activates the tyrosine kinase Janus kinase 2 (JAK2), thus initiating a multitude of signaling cascades that result in a variety of biological responses including cellular proliferation, differentiation and migration, prevention of apoptosis, cytoskeletal reorganization and regulation of metabolic pathways. A number of signaling proteins and pathways activated by GH have been identified, including JAKs, signal transducers and activators of transcription (Stats), the mitogen activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3'-kinase (PI3K) pathway. Although these signal transduction pathways have been well characterized, the manner by which GH activates these pathways, the downstream signals induced by these pathways, and the cross-talk with other pathways are not completely understood. Recent findings have added vital information to our understanding of these downstream signals induced by GH and mechanisms that terminate GH signaling, and identified new GH signaling proteins and pathways. This review will highlight some of these findings, many of which are unexpected and some of which challenge previously held beliefs about the mechanisms of GH signaling.
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PMID:Recent advances in growth hormone signaling. 1730 65

We report an unusual case of bilateral brachial plexus neuritis occurring during the seroconversion stage of an HIV infection in a 45-year-old man. Brachial plexus neuritis is thought to be an immune mediated inflammatory reaction resulting in acute onset of shoulder pain followed by muscle weakness and wasting. There is often a history of viral illness, diagnosis is clinical, and treatment is supportive. Many sufferers are left with residual defects. Clinicians should consider the possibility of HIV infection when managing a patient with brachial plexus neuritis.
Int J STD AIDS 2012 Feb
PMID:Brachial plexus neuritis in the context of acute HIV seroconversion illness: a case report. 2242 93


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