Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indinavir is a protease inhibitor used in the treatment of patients with HIV infection. Combination antiretroviral therapy with indinavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is associated with greater reductions in viral load, greater increases in CD4+ cell counts, and reduced morbidity and mortality when compared with 2 NRTIs alone. In the landmark clinical trial ACTG 320, the rate of progression to AIDS or death (primary end-point) among zidovudine-experienced patients treated with indinavir, zidovudine and lamivudine was approximately half that of patients who received only zidovudine plus lamivudine (6 vs 11%; p < 0.001). The durability of an indinavir-containing regimen was demonstrated in Merck protocol 035, an ongoing trial in which a significant proportion of patients had sustained viral suppression for up to 3 years. Merck protocol 039, also an ongoing trial, showed a greater effect on surrogate markers of HIV disease progression with indinavir-based triple therapy than with zidovudine plus lamivudine or indinavir monotherapy in patients with advanced disease (median baseline CD4+ count 15 cells/microL). Numerous additional clinical trials have established the beneficial antiviral and immunological effects of indinavir in both antiretroviral-naive and -experienced patients with HIV infection. Indinavir is associated with various drug class-related adverse events, including gastrointestinal disturbances (e.g. nausea, diarrhoea), headache and asthenia/fatigue. A lipodystrophy syndrome has been commonly reported with indinavir and other protease inhibitors combined with NRTIs, but it has also been reported in many protease inhibitor-naive patients, and a definitive causal link has not been established between the syndrome and protease inhibitors. Nephrolithiasis may develop in about 9% of patients receiving indinavir but does not appear to be associated with other protease inhibitors; <0.5% of patients receiving indinavir discontinue the drug because of nephrolithiasis, which may be the extreme end of a continuum of crystal-related renal syndromes. Additional renal problems (e.g. nephropathy) have been reported in small numbers of patients receiving indinavir. In summary, indinavir is a protease inhibitor with well documented efficacy when used as part of combined therapy in patients with HIV infection. Both US and UK treatment guidelines continue to recommend protease inhibitor-based regimens including indinavir as a first-line option. Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues. Indinavir-containing triple therapy has demonstrated positive effects not only on surrogate markers of disease progression, but also on clinical end-points of mortality and morbidity in patients with HIV disease. Protease inhibitors are a significant advance in the care of patients with HIV infection, and, in an era of evidence-based medicine, indinavir represents an important component of antiretroviral treatment strategies.
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PMID:Indinavir: a review of its use in the management of HIV infection. 1065 94

Recently ultrasound assisted liposuction (UAL) and pneumatic assisted liposuction (PAL) have been introduced as an attempt to improve the results and reduce the pitfalls of standard liposuction (SAL). Until now no studies comparing, at the same time, UAL, PAL, and SAL have been published. The aim of this study was to analyze these methods from the surgeon's point of view, focusing not only on aesthetic results but also on local and systemic trauma, efficacy, handling, and cost. Forty-five cosmetic patients affected by local lipodystrophy, divided into three equal groups, have undergone liposuction with the three above-mentioned techniques. Quantitative and qualitative analysis of lipoaspirates, together with blood chemistry, local and systemic complications, time to aspirate 100 cm3, distress, fatigue, and costs of the procedures, has been recorded. Our results showed bloodier lipoaspirates in SAL and a higher percentage of triglycerides in UAL lipoaspirates. Blood tests revealed a slight decrease in the postoperative Hb in SAL only. Early complications observed were four erythemas in PAL, three ecchymoses in SAL, and one long-lasting edema in UAL. Aesthetic results rated by independent viewers were similar for all methods. Efficacy was higher in the PAL group (4 min x 100 cm3 fat aspirated) than in SAL (7 min x 100 cm3 fat) and UAL (10 min x 100 cm3 fat). Surgeon's distress was higher in PAL than in SAL and UAL. Surgeon's fatigue was much lower in the PAL group than in the others. Costs expressed as multiples of 1 unit (1 unit = $500 U.S.) were highest for UAL, low for PAL, and lowest for SAL. In conclusion, PAL and UAL caused reduced vascular injury, UAL being more selective for adipocyte removal. Complications of UAL and PAL were mostly related to the longer learning curve of these methods. The UAL procedure was much more expensive than PAL and, especially, SAL. PAL proved to be a handy technique, with the most favorable cost/benefit ratio, and seems to be the best option for busy liposuction practices or fast office procedures, even though the choice of the ideal technique always depends on the surgeon's preference.
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PMID:Comparative evaluation of traditional, ultrasonic, and pneumatic assisted lipoplasty: analysis of local and systemic effects, efficacy, and costs of these methods. 1124 25

The Authors compare the results obtained between two groups of patients suffering from leg lipodystrophy, who were subjected to a reducing lipoplasty. In the first group, surgeons made use of a new sort of cannula, deprived of the classical grip, whereas in the second group, they employed the traditional probe. The best results, achieved with the first group, prove this new operating system is really effective, particularly on legs, for the following reasons: (1) Higher precision and better control of the instrument (2) Swan-neck cannula abolition (3) Opportunity to operate with both hands (4) Halved operating time (5) No tiredness after the operation.
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PMID:Lipoplastics of legs: our experience with a new cannula compared with classical technique. 1124 26

The FDA has approved Agenerase (generic name amprenavir), a new protease inhibitor which costs about $6,500 per year. Eight 150mg gelatin capsules, twice a day, can be taken without food restrictions. Potential side effects include nausea, fatigue, and headache. About 20 percent of patients developed a rash, that was life-threatening in 1 percent. Early data indicate that the drug does not cause lipodystrophy. Drug interactions are possible with some antihistamines, sedatives, and anti-fungal agents. Website contact information is provided.
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PMID:New protease inhibitor. 1136 64

David Morris, 47, is the very picture of successful HIV antiretroviral therapy. He was diagnosed with HIV on Dec. 31, 1983, first began to take AZT in 1985, and now is on an antiretroviral regimen that has kept his viral load to undetectable levels. Moreover, Morris has thus far avoided some of the more serious side effects associated with treatment, including lipodystrophy, bone problems, and increased lipid levels. However, Morris, who is an administrator of the wellness program at Beth Israel Deaconess Medical Center in Boston, sometimes feels as though he is suffering from battle fatigue.
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PMID:18-year survivor discusses HIV battle fatigue. 1156 69

Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy, lipodystrophy, and myopathy. Because not all patients experience these side effects, genetic factors could be involved. It is believed that the main toxicity of nucleoside analog drugs is due to a decrease in mitochondrial function, possibly by inhibition of mitochondrial DNA (mtDNA) replication. mtDNA is replicated by a multienzyme complex, the main component of which is the nuclear-encoded DNA polymerase gamma. Presently, the only known variation in the DNA polymerase gamma gene is variation in the number of CAG repeats in the second exon. To investigate whether CAG repeat expansion or mutations in the DNA polymerase gamma (POLG) gene could predispose to peripheral neuropathy or lactic acidosis, we have sequenced part of the second exon of the DNA polymerase gamma gene, containing the CAG repeat, of 59 drug-treated HIV-infected patients, 11 of whom experienced drug-induced neuropathy, and 3 of whom died from lactic acidosis. No correlation was found between numbers of CAG repeats and any of the symptoms. The coding regions of the POLG gene from the three lactic acidosis patients were then completely sequenced, but no mutations were found. In addition, no variation was detected in exons 3, 8, and 19 of seven neuropathy patients and three control subjects without symptoms. These exons were the only sites of amino acid changes between human and chimpanzee POLG genes, and were chosen as targets of tolerated variation.
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PMID:Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment. 1203 82

The authors examined the impact of potent antiretroviral therapy (ART) on the diagnosis of wasting syndrome in the Multicenter AIDS Cohort Study. Study time was divided into the periods 1988-1990, 1991-1993, 1994-1995, and 1996-1999 to correspond to different treatment eras. The proportion of acquired immunodeficiency syndrome diagnoses in which wasting was present increased from 5% in 1988-1990 to 7.1% in 1991-1993, 7.7% in 1994-1995, and 18.9% in 1996-1999. The incidence of wasting per 1,000 person-years increased from 7.5 in 1988-1990 to 14.4 in 1991-1993 and 22.1 in 1994-1995; it decreased to 13.4 in 1996-1999. Fewer patients with wasting had low hemoglobin and hematocrit levels and reported oral thrush in 1996-1999 than in any other period. Analysis of change in body mass index (weight (kg)/height (m)(2)) after wasting showed a faster return to prewasting levels in 1994-1995 and 1996-1999 than in earlier periods. Case-control analysis showed that wasting prior to 1996 was weakly associated with fatigue (p = 0.10), low hemoglobin (p = 0.11), and CD4-positive T-lymphocyte count (p = 0.04). During 1996-1999, wasting was weakly associated with diarrhea (p = 0.05) and potent ART (p = 0.097). Predictors of wasting have changed with potent ART. Further research is needed to determine whether lipodystrophy may be misdiagnosed as wasting syndrome.
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PMID:Changes in the incidence and predictors of wasting syndrome related to human immunodeficiency virus infection, 1987-1999. 1214 55

Skeletal muscle involvement can occur at all stages of human immunodeficiency virus (HIV) infection, and may represent the first manifestation of the disease. Myopathies in HIV-infected patients are classified as follows: (1) HIV-associated myopathies and related conditions, including HIV polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitic processes, myasthenic syndromes, and chronic fatigue; (2) muscle complications of antiretroviral therapy, including zidovudine and toxic mitochondrial myopathies related to other nucleoside-analogue reverse-transcriptase inhibitors (NRTIs), HIV-associated lipodystrophy syndrome, and immune restoration syndrome related to highly active antiretroviral therapy (HAART); (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. Introduction of HAART has dramatically modified the natural history of HIV disease by controlling viral replication, but, in turn, lengthening of the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions.
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PMID:Skeletal muscle involvement in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART). 1590 90

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

Introduction of highly active antiretroviral therapy (HAART) has dramatically modified the natural history of HIV disease, but lengthening the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions. Muscular complications of HIV infection are classified as follows: (1) HIV-associated myopathies and related conditions including polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitis, myasthenic syndromes, and chronic fatigue; (2) iatrogenic conditions including mitochondrial myopathies, HIV-associated lipodystrophy syndrome, and immune restoration syndrome; (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. These features are described in the present review.
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PMID:[Muscular complications of human immunodeficiency virus (HIV) infection in the era of effective anti-retroviral therapy]. 1644 25


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