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To evaluate the nutritional, metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids (fish oil) supplementation in immunocompromised patients, we performed a prospective study on the effect of immune formula administered to 11 severe trauma patients (average ISS = 24), 10 burn patients (average % TBSA = 48) and 5 cancer patients. Daily calorie and protein administration were based on the patient's severity (Stress factor with the range of 35-50 kcal/kg/day and 1.5-2.5 g/kg/day, respectively) Starting with half concentration liquid immune formula through nasogastric tube by continuous drip at 30 ml/h and increasing to maximum level within 4 days. The additional energy and protein requirement will be given either by parenteral or oral nutritional support. Various nutritional, metabolic, immunologic and clinical parameters were observed on day 0 (baseline), day 3, 7, and 14. Analysis was performed by paired student-t test. Initial mean serum albumin and transferrin showed mild (trauma) to moderate (burn and cancer) degree of malnutrition. Significant improvement of nutritional parameters was seen at day 7 and 14 in trauma and burn patients. Significant increase of total lymphocyte count (day 7, P < 0.01), CD4 + count (day 7, p < 0.01), CD8 + count (day 7, p < 0.0005 & day 14, p < 0.05), complement C3 (day 7, p < 0.005 day 14, p < 0.01), IgG (day 7, and 14, p < 0.0005), IgA (day 7, p < 0.0005 & day 14, p < 0.05), in all patients. C-reactive protein decreased significantly on day 7 (p < 0.0005) and day 14 (p < 0.005). 3 cases of burn wound infection, one case of UTI and one case of sepsis were observed. Two cases of hyperglycemia in burn, 3 cases of hyperbilirubinemia in trauma, 10 cases of elevated LFT (5 trauma/5 burn), and one case of hyponatremia in cancer patients were observed. Two cases of nausea, 4 cases of vomiting, 5 cases of diarrhea (< 3 times/day), 2 cases of abdominal cramp, 1 case of distension were observed. The feeding of IMMUNE FORMULA was well tolerated and significant improvement was observed in nutritional and immunologic parameters as in other immunoenhancing diets. Further clinical trials of prospective double-blind randomized design are necessary to address the so that the necessity of using immunonutrition in critically ill patients will be clarified.
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PMID:Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids supplementation in immunocompromised patients. 962 33

A 38-year-old homosexual male with AIDS suffered four neurological episodes including headaches, confusion, visual impairment, memory disturbances, and dysarthria which resolved spontaneously in a few days. He was admitted to hospital during a fifth episode. Neurological examination revealed a cerebellar syndrome. General examination was normal. CD4 count was 90. CSF contained two WBCs/mm(3) and 12.30 mg/dL protein. MRI revealed diffuse ill defined increased signal on T2-weighted images in the white matter. His condition worsened rapidly with vomiting and he died 1 month after admission. Neuropathological examination revealed diffuse brain oedema with ventricular compression, central diencephalic herniation and bilateral tonsilar herniation in the absence of a focal lesion. Microscopical examination revealed predominant involvement of the white matter with diffuse myelin pallor and massive perivascular dilatation containing an exudate expressing serum proteins and occasional macrophages. The same exudate was also diffuse in the leptomeninges. Parenchymal damage predominated around the perivascular spaces and included loosening of tissue, axonal damage with spheroids and reactive astrocytosis. There was no evidence of productive HIV encephalitis, no multinucleated giant cells; p24 immunostaining and RT-PCR for HIV genome were negative. There was neither significant inflammation nor microglial activation. In this illustrative case, the relapsing course of the neurological signs, the diffuse topography of the blood-brain barrier breakdown and the absence of local cause make it likely that the diffuse leak and axonal damage could be related to circulating factors.
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PMID:Acute, relapsing brain oedema with diffuse blood-brain barrier alteration and axonal damage in the acquired immunodeficiency syndrome. 971 86

There is no consensus regarding the specific management of HIV-associated nephrotic syndrome. We report a child whose first manifestation of human immunodeficiency virus type 1 (HIV-1) infection was nephropathy and wasting syndrome associated with profound immunodeficiency. The patient had a dramatic clinical and immunologic response to triple antiretroviral therapy delivered through a gastrostomy tube, with complete resolution of nephrotic syndrome. A 51/2-year-old African-American girl presented with a 2-week history of cough, chest pain, vomiting, loose stools, abdominal distention, anorexia, and fever. In addition, she had recurrent oral thrush. Her weight and height were below the 5th percentile. She was chronically ill, appearing with oropharyngeal thrush and pitting edema in lower extremities. She had scattered rhonchi and decreased breath sounds on both lung bases. Her abdomen was distended and diffusely tender. A chest radiograph showed consolidation of the right upper and left lower lobes with bilateral pleural effusion. Admission laboratories were consistent with nephrotic syndrome. Streptococcus pneumoniae grew from the blood culture and the child responded well to treatment with intravenous ceftriaxone. She was found to be HIV-infected, her CD4(+) cell count was 3 cells/mcL and her plasma HIV-1 RNA was >750 000 copies/mL. A percutaneous gastrostomy tube was placed for supplemental nutrition. She was treated with stavudine, lamivudine, and nelfinavir via gastrostomy tube with good clinical response. Twenty-one months after instituting antiretroviral therapy, her weight and height had increased to the 50th and 10th percentile respectively, and she had complete resolution of her nephrotic syndrome. Her CD4(+) cell count increased to 1116 cells/mcL and her viral load has remained undetectable. HIV-1 associated nephrotic syndrome has been described in children with profound immunodeficiency. The course of untreated HIV-associated nephrotic syndrome is rapid progression to renal failure in up to 40% of the children. Regardless of the presence of renal insufficiency, if untreated, it is uniformly fatal. A modest improvement of HIV-1 associated nephrotic syndrome has been observed in patients treated with zidovudine. Steroid and cyclosporine treatment have resulted in improved renal function but long-term use of immunosuppressive therapy has raised concerns about safety. We have described, to our knowledge, the first child with HIV-associated nephrotic syndrome who had a remarkable clinical, immunologic, and virologic response to triple-drug combination therapy given by gastrostomy tube, with complete resolution of proteinuria and normalization of the serum albumin. She also had a striking improvement in weight, height, and quality-of-life. Whether the presence of a gastrostomy tube contributed to the excellent response because of improved compliance is unknown, but warrants systematic evaluation.
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PMID:Resolution of HIV-associated nephrotic syndrome with highly active antiretroviral therapy delivered by gastrostomy tube. 1058 95

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0-infinity). A significant correlation was observed between C(max) and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV-1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0-infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB values for CD4(+) cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.
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PMID:Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects. 1089 75

A 40-year-old HIV-infected woman developed nausea, vomiting, and epigastric pain and died following her third dose (per study protocol) of interleukin (IL)-2. Her HIV infection was diagnosed in 1996. Her last CD4 cell count was 390/microL, and her viral load was negligible (as of November 28, 1998). She had no known general risk factors for thrombosis other than HIV infection, injection drug abuse, and antiretroviral therapy with indinavir. Abdominal films showed no sign of mechanical obstruction but a generalized gas distention of the bowel, which was suggestive of paralytic ileus. Autopsy revealed dilation of the small bowel with extensive necrosis and hemorrhage involving all the segments. The superior and inferior mesenteric arteries revealed severe atherosclerosis. The stenotic celiac artery was occluded by a recent thrombus at the aortic ostium. Clinicians need to be aware of the potential for thrombosis and accelerated atherosclerosis in HIV-infected patients. Both injection drug abuse and protease inhibitors, such as indinavir, have been shown to be risk factors for thrombosis. However, it is likely IL-2 contributed to the severe thrombosis in this patient, although definitive proof is lacking. An acute awareness of intestinal infarction in HIV-infected patients is warranted.
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PMID:Case report. Intestinal infarction due to vascular catastrophe in an HIV-infected patient. 1118 43

The nucleoside reverse transcriptase inhibitor 3TC (lamivudine) appears to induce unusually prolonged HIV suppression when used in combination with AZT, according to the results of four randomized clinical trials. The studies showed that 3TC and AZT had similar antiviral effects when used alone. However, investigators observed a substantial, prolonged increase in CD4 counts and a significant decrease in HIV RNA when the drugs were administered simultaneously. These benefits persisted in all study groups for the 24-week study period, and in several for the six-month follow-up period as well. The combination was well-tolerated by nearly 1000 AZT-naive and AZT-experienced subjects enrolled in these trials, with the most common adverse effects being nausea, vomiting and headaches. A possible explanation for the antiviral effect is suggested by the mutation at HIV codon 184 that is frequently observed in virions exposed to 3TC for extended periods of time. In vitro studies have shown that this mutation confers 3TC resistance. It may also counteract other mutations that would normally lead to AZT resistance, therefore enabling virions exposed to both drugs to remain effectively susceptible to AZT.
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PMID:Combination 3TC/AZT therapy shows promise. 1136 92

Glaxo Wellcome is offering an expanded access program for abacavir (Ziagen, formerly 1592) to HIV-positive patients who are not benefiting from their current combination therapy. In a dramatic departure from the usual entry criteria, the abacavir eligibility criteria require no specific CD4 cell count or viral load. To qualify, volunteers must be on a failing regimen, unable to tolerate standard therapies, and a physician must verify that another drug combination would not be viable. Patients are urged to switch to a regimen of at least two new drugs based on U.S. government treatment guidelines. Similar programs are available for the anti-HIV drugs efavirenz (Sustiva) and adefovir dipivoxil (Preveon). People using abacavir, a nucleoside analog, may experience side effects such as headache, nausea, and vomiting. If a hypersensitivity reaction develops, patients must stop the treatment. Taking the drug after experiencing an adverse reaction can be life threatening.
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PMID:Glaxo opens broad expanded access program for abacavir (Ziagen). 1136 71

This paper discusses the introduction of antiretroviral (ARV) therapy to HIV-infected patients. ARV therapy is treatment with drugs that fight the HIV virus and keep the HIV-infected patient healthy. Treatment may involve only one ARV (monotherapy) or a combination of two or more ARVs (combination therapy). The increasing availability of ARVs in many countries has caused dangerous side effects to develop quickly in patients due to the improper use of drug combinations. Some life-threatening side effects of ARV misuse include vomiting, diarrhea, fever, diabetes, and pancreatitis. People who experience these symptoms need to change their drug combination; a drug must be taken with strict instructions to prevent unpleasant side effects and its reaction with other drugs (protease inhibitors, for example, react with the tuberculosis drug rifampicin). An ARV should also be closely monitored to ensure its continuous effectiveness using CD4 and viral load counts at least every 3-6 months. A change in drug combination is required when CD4 count is dropping or the viral load is not reduced or maintained.
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PMID:Introducing antiretroviral therapy. 1234 94

The difference between adherence to non- nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)-based regimens was investigated. Better adherence was found in NNRTI-treated patients, especially when efavirenz was included in the regimen, compared with single PI-treated patients and in those with CD4 cell counts less than 200 x 10(6)/l. By contrast, younger age, self-report of active drug use, fatigue or vomiting negatively affected adherence. Self-reported sexual dysfunction was significantly associated with non-adherence only in PI-treated individuals.
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PMID:Adherence to highly active antiretroviral therapy is better in patients receiving non-nucleoside reverse transcriptase inhibitor-containing regimens than in those receiving protease inhibitor-containing regimens. 1270 Apr 67

Symptom recognition is critical for patient care but has been little studied in older HIV-infected individuals. The authors examined differences in symptom expression between younger (younger than age 50 years) and older (older than age 50 years) HIV-infected individuals. The authors analyzed data from two cross-sectional studies of HIV-infected individuals: 2864 individuals from the HIV Cost and Service Utilization Study (HCSUS) and 881 individuals from the Veterans Aging Cohort 3 Site Study (VACS 3). The authors compared the prevalence of eight symptoms common to both studies and 10 symptoms examined only in the VACS 3 population, stratified by age and race. Disease severity was assessed by CD4 count and 18 HIV-related diseases reported. Multivariate logistic regression models were used to account for demographics and severity differences. VACS 3 versus HCSUS participants were more likely nonwhite and older. In unadjusted comparisons, older nonwhites were less likely to report experiencing symptoms than younger whites. They reported the fewest total number of symptoms and the fewest individual symptoms common to both studies (headache, fever, nausea/vomiting, and diarrhea) or in the VACS 3 only (dizziness, sleeping difficulty, fatigue, rashes, bloating, and myalgias/arthalgias). Multivariate regression estimates suggest older age predicts a greater likelihood of reporting peripheral neuropathy, weight loss, or hair loss, but a lower likelihood of reporting headaches, depressed mood, white oral patches, or diarrhea. Nonwhites appeared less likely to report symptoms. Age is a determinant of reporting certain symptoms in HIV disease but may be masked or accentuated by other factors such as race.
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PMID:Differences in symptom expression in older HIV-positive patients: The Veterans Aging Cohort 3 Site Study and HIV Cost and Service Utilization Study experience. 1285 57


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