Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical manifestations of primary human immunodeficiency virus (HIV) infection (acute retroviral syndrome) and virologic characteristics of HIV-1 have rarely been described in Taiwan. Medical records of patients followed at the National Taiwan University Hospital between June 1994 and September 2003 were retrospectively reviewed to identify HIV-infected patients who were diagnosed with primary HIV infection. Blood specimens obtained at the diagnosis of primary HIV infection were submitted for viral subtyping and genotypic resistance assay. Twenty out of 940 patients were diagnosed with acute retroviral syndrome during the study period. All of the patients were males, with a median age of 31 years (range, 23 to 42 years); all were men who had sex with men. The most common clinical manifestations were fever (95%), generalized lymphadenopathy (75%), pharyngitis (70%), skin rashes (70%), and gastrointestinal symptoms (60%) including nausea, vomiting, and diarrhea. Thrombocytopenia (35%), leukopenia (35%), and elevated liver function test (50%) were seen in the laboratory tests. The median CD4 lymphocyte count was 312 cells/microL (range, 112-520 cells/microL), and the plasma HIV RNA load by reverse transcriptase-polymerase chain reaction was 230,500 copies/mL (range, 602 --> 750,000 copies/mL). No major resistance mutations on protease or reverse transcriptase were identified in the 11 available viral isolates. We conclude that primary HIV infection was rarely diagnosed in the designated hospital for HIV care in Taiwan. More education of health care providers and counseling of persons at risk to increase awareness of HIV infection are urgently needed in Taiwan in order to facilitate earlier diagnosis of primary HIV infection and prevent further transmission.
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PMID:Clinical presentations and virologic characteristics of primary human immunodeficiency virus type-1 infection in a university hospital in Taiwan. 1549 7

Capravirine is a nonnucleoside reverse-transcriptase inhibitor (NNRTI) with a unique resistance profile. Although single mutations allow resistance to established NNRTIs, human immunodeficiency virus (HIV)-1 must undergo multiple mutations to achieve resistance to capravirine. In the present phase 1 study, capravirine was administered orally for up to 28 days to 55 HIV-1-infected individuals with CD4+ T lymphocyte counts of 50-500 cells/microL. The most frequent adverse events were diarrhea (5%) and nausea (4%), with no drug-related rashes observed. The day 15 median (mean) HIV-1 load decreased by 1.34 (1.45) log(10) copies/mL in the patients receiving 25 mg/kg/day. Capravirine demonstrated potent antiviral activity, even in antiretroviral-experienced patients.
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PMID:Capravirine, a nonnucleoside reverse-transcriptase inhibitor in patients infected with HIV-1: a phase 1 study. 1552 60

Atazanavir is the first once-daily protease inhibitor for the treatment of human immunodeficiency virus type 1 infection and should be used only in combination therapy, as part of a highly active antiretroviral therapy (HAART) regimen. In addition to being the most potent protease inhibitor in vitro, atazanavir has a distinct cross-resistance profile that does not confer resistance to other protease inhibitors. However, resistance to other protease inhibitors often confers clinically relevant resistance to atazanavir. Currently, atazanavir is not a preferred protease inhibitor for initial HAART regimens. In treatment-naive patients, atazanavir can be given as 400 mg/day. However, atazanavir should be pharmacologically boosted with ritonavir in treatment-experienced patients or when coadministered with either tenofovir or efavirenz. Patients who receive atazanavir experience similar rates of adverse events compared with patients receiving comparator regimens. An exception is an increased risk of asymptomatic hyperbilirubinemia, which is due to competitive inhibition of uridine diphosphate-glucuronosyltransferase 1A1. Although hyperbilirubinemia is a common adverse drug reaction of atazanavir therapy (22-47%), fewer than 2% of patients discontinue atazanavir therapy because of this adverse effect. Common adverse effects reported with atazanavir include infection, nausea, vomiting, diarrhea, abdominal pain, headache, peripheral neuropathy, and rash. Of significance, fewer abnormalities have been observed in plasma lipid profiles in patients treated with atazanavir compared with other protease inhibitor-containing regimens. As with other protease inhibitors, atazanavir is also a substrate and moderate inhibitor of the cytochrome P450 (CYP) system, in particular CYP3A4 and CYP2C9. Clinically significant drug interactions include (but are not limited to) antacids, proton pump inhibitors, histamine type 2 receptor antagonists, tenofovir, diltiazem, irinotecan, simvastatin, lovastatin, St. John's wort, and warfarin. We conclude that atazanavir is a distinctively characteristic protease inhibitor owing to its in vitro potency, once-daily dosing, distinct initial resistance pattern, and infrequent association with metabolic abnormalities.
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PMID:Atazanavir for the treatment of human immunodeficiency virus infection. 1558 41

A phase I, open-label, dose-escalating trial was conducted to evaluate the safety, tolerability, and pharmacokinetics of single, oral doses of amprenavir (141W94), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease, in 20 HIV-infected children 4 to 12 years of age. The doses of amprenavir evaluated, 5, 10, 15, and 20 mg/kg of body weight, were comparable to those evaluated in adult phase I and II studies. The most common clinical adverse event associated with amprenavir, administered as soft gelatin capsules, was nausea. Amprenavir was rapidly absorbed, with a mean time to maximum concentration (T(max)) occurring 0.95 to 1.58 h after dosing. The area under the concentration-time curve (AUC(0)(-->)(infinity)) was dose proportional, and the mean maximum plasma concentration (C(max)) increased linearly in a less than dose-proportional manner. Amprenavir was eliminated relatively slowly, with a mean terminal-phase half-life (t(1/2)) of 6.17 to 8.28 h. The t(1/2), apparent total clearance, and apparent volume of distribution during the elimination phase were dose independent. Considerable interpatient variability was seen for all pharmacokinetic parameters of amprenavir. The results of this study suggest that 20 mg of amprenavir/kg administered twice a day should be used in future pediatric studies.
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PMID:Single-dose safety and pharmacokinetics of amprenavir (141W94), a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, in HIV-infected children. 1561 13

Nucleoside reverse-transcriptase inhibitors (NRTIs) have been associated with functional and structural mitochondrial abnormalities, leading to several adverse events, such as increased serum lactic acid levels and lactic acidosis. Mild-to-moderate, asymptomatic hyperlactataemia has been frequently reported in human immunodeficiency virus (HIV)-infected patients treated with NRTIs, with an estimated prevalence between 15% and 35%. On the contrary, symptomatic, severe hyperlactataemia and lactic acidosis are less common, with an incidence ranging from 1.7 to 25.2 cases per 1000 person-years of antiretroviral treatment, and are associated with a remarkable mortality rate, which varies from 30% to 60% in different studies. The clinical presentation of lactic acid syndrome is non-specific and includes asthenia, malaise, nausea, vomiting, abdominal pain, weight loss, tachypnoea, dyspnoea, liver steatosis and increased transaminase levels, and risk factors include previous or concurrent therapy with stavudine or didanosine. Management of symptomatic lactic acid alterations involves NRTI-therapy interruption and supportive care, while natural history of hyperlactataemia is still unknown, and it is uncertain whether asymptomatic patients with increased lactate concentrations are at increased risk of developing lactic acidosis.
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PMID:Hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral therapy. 1568 Oct 97

A promising approach to improving outcomes in patients with cryptococcal meningitis is to use adjunctive passive immunotherapy with a monoclonal antibody (MAb) directed against the capsular polysaccharide of Cryptococcus neoformans. This is the first application of MAb therapy for the treatment of a fungal disease in humans. We determined the safety and maximum tolerated dose of the murine anticryptococcal MAb 18B7 in a phase I dose-escalation study. The subjects were human immunodeficiency virus-infected patients who had been successfully treated for cryptococcal meningitis. Six dosing cohorts received MAb 18B7 at 0.01 to 2 mg/kg of body weight as a single infusion. Three patients each received 0.01, 0.05, 0.2, and 0.5 mg of MAb 18B7 per kg without significant adverse events. Four of the subjects who received the 1-mg/kg dose had mild study drug-associated toxicity, including transient nausea, vomiting, back pain, and urticarial rash. Two of the subjects who received 2 mg/kg developed drug-associated mild to moderate nausea, vomiting, chills, and myalgias. One of the subjects who received 2 mg/kg developed intracranial hypertension 10 weeks after MAb 18B7 administration. Serum cryptococcal antigen titers in the cohorts receiving doses of 1 and 2 mg/kg declined by a median of twofold at 1 week and a median of threefold at 2 weeks postinfusion, but the titers subsequently returned toward the baseline values by week 12. The half-life of MAb 18B7 in serum was approximately 53 h, while the MAb was undetectable in the cerebrospinal fluid of all patients. These data support the continued investigation of MAb 18B7 at a maximum single dose of 1.0 mg/kg.
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PMID:Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. 1572 88

873140 is a novel CCR5 antagonist with potent in vitro anti-human immunodeficiency virus (HIV) activity. This study was a double-blind, randomized, placebo-controlled, single- and repeat-dose escalation investigation of the safety, pharmacokinetics, and food effect of 873140 in 70 adult subjects. During single-dose escalation, three cohorts (each composed of 10 subjects, with 8 subjects receiving the active drug and 2 subjects receiving the placebo [8 active and 2 placebo]) received doses of 50, 200, 400, 800, and 1,200 mg after an overnight fast, or 400 mg plus a standard high-fat breakfast in an alternating panel design. During repeat-dose escalation, four cohorts (each with 8 active and 2 placebo) received doses of 200, 400, 600, or 800 mg every 12 h (BID) for 8 days. Laboratory safety tests, vital signs, and electrocardiograms (ECGs) were performed at regular intervals, and blood samples were obtained for pharmacokinetics. Single and repeat doses of 50 mg to 800 mg were well tolerated, with no serious adverse events and no grade 3 or 4 adverse events. The mild-to-moderate side effects were primarily gastrointestinal and included abdominal cramping, nausea, and diarrhea. No specific trends in laboratory parameters or clinically significant ECG changes were noted. Plasma 873140 concentrations increased rapidly; the median time to maximum concentration of drug in serum was 1.75 to 5 h. The median area under the plasma concentration-time profile (AUC) and the maximum concentration of drug in serum (C(max)) ranged from 127 ng.h/ml and 24 ng/ml at 200 mg BID to 329 ng.h/ml and 100 ng/ml at 800 mg BID, respectively. Food consumption increased the AUC and C(max) by a mean of 1.7- and 2.2-fold, respectively. The pharmacokinetic and safety profile supports the continued investigation of 873140 with HIV-infected subjects.
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PMID:Pharmacokinetics and short-term safety of 873140, a novel CCR5 antagonist, in healthy adult subjects. 1598 Mar 52

A 39-yr-old male with hepatorenal syndrome type 1 and refractory ascites was treated with continuous renal replacement therapy (CRRT) resulting in clinical improvement. He was positive for antibodies to hepatitis B, C, and human immunodeficiency viruses, and had a history of chronic alcohol and iv drug abuse. The patient had 4 hospital admissions during a 12-wk period. He first presented with advanced liver disease including pedal edema and a serum ammonia level of 56 micromol/L (reference range: 11 - 35 micromol/L). In subsequent admissions, he had asterixis, nausea, vomiting, jaundice, and worsening pedal edema. On his 4th admission, there was lethargy, tense ascites, decreased urinary output, bilateral edema of the lower extremities and scrotum, serum creatinine of 6.2 mg/dl (reference range: 0.6 - 1.5 mg/dl), and weight gain of 16 kg during the prior 8 wk. During the first 3 hospitalizations, he was treated with lactulose with slight improvement. On the 4th admission, he was started on low-dose dopamine (3 microg/kg/min) and 25% salt-poor albumin without clinical improvement. A pulmonary artery catheter was placed and hemofiltration by CRRT was performed for 5 days, with removal of 26.7 L of fluid and a net reduction of 11 kg of body weight. Serum creatinine decreased to 4.2 mg/dl during CRRT and was 2.2 mg/dl at hospital discharge 2 weeks later. His PaO(2) improved from 66 to 78 mmHg and his systemic vascular resistance increased from 571 to 799 dyne.sec/cm(5). CRRT was effective in relieving severe fluid retention and producing marked clinical improvement. We suggest that CRRT should be considered for the treatment of refractory ascites including that caused by hepatorenal syndrome.
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PMID:Hepatorenal syndrome: resolution of ascites by continuous renal replacement therapy in an alcoholic coinfected with hepatitis B, C, and human immunodeficiency viruses. 1650 Dec 43

We report an immunodeficient patient with a rare gastrointestinal manifestation. A 26-year-old male with common variable immunodeficiency (CVID) and bronchiolitis obliterans, who was on intravenous gamma-globulin and prednisone, presented diffuse abdominal pain, nausea, vomiting and constipation of 3 days' duration. He reported 5 years of recurrent respiratory infections and diarrhea with negative stool tests, including tests for Strongyloides stercoralis. A physical exam revealed a poor general condition, anemia, dehydration and a distended painful abdomen with guarding, without abdominal sounds. The radiological study showed marked dilation of the small bowel that was edematous. Resection of the affected loop was performed and the histopathologic study showed transmural infection with S. stercoralis and hemorrhagic necrosis of the muscular layer, without mucosal destruction. The patient developed malabsorption syndrome and septic shock; he was treated with antibiotics and thiabendazole and was finally discharged in a good general condition. CVID is a rare disease and its association with systemic strongyloidiasis is very uncommon, but it has been reported in patients on corticosteroids. Hemorrhagic necrosis of the muscular layer without mucosal destruction was not found in the literature studied.
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PMID:A rare intestinal manifestation in a patient with common variable immunodeficiency and strongyloidiasis. 1668 1

The i.v. immunoglobulin (IVIG) therapy is one of the mainstays of treatment for humoral immunodeficiencies, but there is limited knowledge of the adverse reactions associated with this therapy, especially reactions occurring in the postinfusion period. The purpose of this prospective, observational, multicenter study was to identify and quantify the adverse reactions that can occur both during and after IVIG infusions (Gamimune N) in patients with humoral immunodeficiency. Patients with primary immunodeficiencies requiring IVIG therapy were followed over a 6-month period, and data regarding adverse events, particularly the time of onset, duration, and type of reaction associated with IVIG infusions wzas collected via direct observation and patient interviews. Data were obtained during and up to 72 hours after the completion of infusions. Sixty-five patients were recruited and received a total of 447 infusions over a 6-month period. Four hundred fifty-one adverse reactions were noted, with 17% of infusions associated with an intrainfusion reaction and 41% associated with a postinfusion reaction. Most postinfusion reactions occurred within 24 hours of the infusion and consisted mainly of headaches, fatigue, and nausea. Adverse reactions to Gamimune N infusions are common and occur primarily in the postinfusion period. Estimates of the rate of adverse reactions to Gamimune N infusions currently are underestimated because they do not account for postinfusion reactions. In addition, once recognized, effective treatment of postinfusion reactions may improve patient compliance and quality of life.
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PMID:Intrainfusion and postinfusion adverse events related to intravenous immunoglobulin therapy in immunodeficiency states. 1717 91


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