Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and the reverse transcriptase of human immunodeficiency virus (HIV) are selectively inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is reversible on withdrawal of foscarnet and additive or synergistic effects have been demonstrated in vitro with other antiviral drugs, including ganciclovir and zidovudine. Foscarnet appears to have negligible effects on host enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more than 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis during foscarnet induction therapy, but relapse occurs soon after ceasing treatment. Maintenance treatment given daily can extend the period of remission considerably. Foscarnet and ganciclovir monotherapy had similar efficacy in the treatment of CMV retinitis in patients with AIDS in several studies, and have been used concomitantly in immunocompromised patients with recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived for significantly longer than those receiving ganciclovir. Foscarnet has been used successfully in the treatment of limited numbers of immunocompromised patients with CMV-associated gastrointestinal (improvement in over 67% of patients) and other infections. Aciclovir-resistant herpes simplex infections in immunocompromised patients have also been treated successfully with foscarnet. Almost 90% of a foscarnet dose is excreted in the urine. Reversible nephrotoxicity is common during foscarnet therapy, but may be reduced by dosage adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in electrolyte levels and genital ulceration have also been associated with administration of the drug. The different tolerability profiles of foscarnet and zidovudine facilitate the use of these agents in combination in patients with AIDS and CMV infection; whereas ganciclovir, like zidovudine, is associated with dose-limiting haematological toxicity. The apparent survival benefits seen in these patients when receiving foscarnet and zidovudine (possibly linked to synergy between zidovudine and foscarnet and/or the inherent anti-HIV activity of foscarnet), appear to offer potentially important advantages for foscarnet over ganciclovir in the treatment of selected patients with AIDS and CMV infections.
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PMID:Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. 752 25

Azithromycin has in vitro activity against Treponema pallidum and is effective against experimental syphilis in rabbits. We undertook an open, noncomparative pilot study of oral azithromycin (500 mg once daily for 10 days) to treat 16 patients with primary or secondary syphilis who were seronegative for human immunodeficiency virus. Cure was documented for 11 of 13 patients observed > or = 3 months; three patients were lost to follow-up. The serological response of one patient with secondary syphilis was indeterminate, and one patient with primary syphilis had either relapse or reinfection. Four patients had mild gastrointestinal side effects, and another patient had an episode of nausea and vomiting; all side effects occurred in the first 3 days and resolved spontaneously as treatment continued. Azithromycin shows promise as an alternative agent for treatment of early syphilis; controlled trials and assessment of other dosage regimens are indicated.
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PMID:Pilot study of azithromycin for treatment of primary and secondary syphilis. 781 68

The yield of upper gastrointestinal endoscopy (esophago-gastroduodenoscopy; EGD) in human immunodeficiency virus (HIV)-infected patients based on presenting symptoms has not been well studied. We studied consecutive patients with documented HIV infection undergoing EGD at a large innercity hospital between August 1, 1990 and December 31, 1993; all had presenting symptoms and indications for EGD prospectively recorded at the time of EGD. All endoscopic abnormalities were routinely subjected to biopsy, and extensive histopathological evaluation was performed. EGD was considered helpful when the findings stimulated specific therapeutic intervention other than antifungal or antacid medications. The specific indications for EGD in 156 patients were as follows: esophageal symptoms, 102 patients (65%); abdominal pain, 18 (12%); upper gastrointestinal bleeding, 25 (16%); refractory nausea and vomiting, 11 (7%). Overall, pathologic findings were identified in 116 patients (74%): in refractory esophageal symptoms, 82%; upper gastrointestinal bleeding, 92%; abdominal pain, 39%; nausea and vomiting, 27%. EGD with biopsy identified a specifically treatable opportunistic disorder other than Candida in 80 patients (51%), including idiopathic esophageal ulcer (22%) or viral esophagitis and/or duodenitis (29%). EGD was not helpful in 22.3% of cases, those involving Candida (12.3%) and peptic ulcer disease (PUD)-related causes (10%). The mean CD4 count of patients with opportunistic pathologic findings (24/mm3, n = 79) was significantly lower than that of patients with PUD/gastroesophageal reflux disease (GERD) (167/mm3, n = 9) or negative EGDs (165/mm3, n = 35). Overall, the results of EGD influenced patient management in 78% of cases. We conclude that selective symptom-specific use of EGD, particularly in patients with esophageal symptoms refractory to antifungal therapy or gastrointestinal bleeding, usually identifies specifically treatable abnormalities, whereas EGD is less useful for the evaluation of abdominal pain or nausea and vomiting.
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PMID:Symptom-specific use of upper gastrointestinal endoscopy in human immunodeficiency virus-infected patients yields high dividends. 895 33

Ondansetron was the first of several selective 5-hydroxytryptamine (5-HT3) antagonists to be available as an antiemetic. Its uses in the setting of highly and moderately emetogenic chemotherapy and radiotherapy are well established. Ondansetron has also been used to manage nausea and vomiting in other patients. We report a retrospective analysis of its use in all 16 patients who were commenced on ondansetron after admission to our institution for nausea and/or vomiting over a 4-year period. Nine patients had advanced human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and seven had malignancy. These patients were not undergoing disease-modifying treatment and had inadequate responses to therapeutic doses of standard antiemetics, used either singly or in combination. Responses were independently reviewed and graded by two investigators. Response was judged at 48 hr after commencing therapy. Potential causes of nausea were also reviewed. Overall, 13 of 16 [81%, 95% confidence interval (CI) 54%-96%] derived benefit. Twelve of 15 patients (80%) with nausea had a demonstrable improvement, and ten of 14 patients (71%) with vomiting also improved. Eight of ten patients (80%) admitted with nausea and/or vomiting as one of their presenting problems had the symptom controlled within 48 hr of ondansetron therapy. Treatment with ondansetron was well tolerated, onset of action was rapid, and response rates were high and sustained over time. Seven of the 16 patients continued ondansetron therapy for more than 10 days. With minimal reductions in inpatient bed stays, the total costs of ondansetron could be met while at the same time better supporting patients remaining in the community.
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PMID:Use of ondansetron in palliative medicine. 918 36

Endoscopy plays a pivotal role in the management of patients with the acquired immunodeficiency syndrome (AIDS), because tissue documentation of opportunistic processes is often necessary to establish a definitive diagnosis. With progression of immunodeficiency, endoscopy becomes more important because the predisposition to opportunistic disorders of the gastrointestinal tract is greatly increased. The yield of upper endoscopy in human immunodeficiency virus (HIV)-infected patients is dependent upon the indication for the procedure, including the clinical presentation and the stage of immunodeficiency. Indications for which endoscopy has a high yield include AIDS with esophageal symptoms refractory to empirical antifungal therapy, small bowel biopsy for chronic severe diarrhea and upper gastrointestinal bleeding. Although processes can be identified, a diagnosis is less likely in patients who present with nausea and vomiting or nonspecific abdominal pain. By tailoring the use of endoscopy to the presenting symptoms and CD4 lymphocyte count, the diagnostic benefit can be increased.
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PMID:Role of endoscopy in the investigation of upper gastrointestinal symptoms in HIV-infected patients. 1036 Sep 90

The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two patients. Seventy-two percent of cases presented some form of toxic effect (NCI-CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas thrombocytopenia was documented in 17% of the patients. The main nonhematologic toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The overall objective response rate was 83%, with 2 complete remissions documented (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20 hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08 l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of fractionated oral daily doses of etoposide produced significant antitumor activity with manageable clinical toxicity in the individuals with AIDS-KS included in this trial. This more favorable therapeutic index of etoposide could be due to the achievement of more sustained plasma levels of the drug within safe but active concentrations.
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PMID:Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index. 1131 95

A 38-year-old woman with human immunodeficiency virus who was recently diagnosed with gastric ulcer presented to the hospital with nausea and vomiting of 1 month's duration. Work-up of patient led to a diagnosis of diffuse, large B-cell non-Hodgkin's lymphoma. The patient underwent six cycles of chemotherapy, and repeated endoscopy and biopsy failed to reveal malignancy. She remains in remission 23 months posttreatment. Management of patients with human immunodeficiency virus and concurrent malignancy remains a challenge. The primary care physician plays a central role by collaborating with infectious disease and oncologist specialists to formulate a management plan.
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PMID:Non-Hodgkin's lymphoma in a patient with human immunodeficiency virus. 1132 14

In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.
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PMID:Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. 1194 51

Patients with human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) can present with acute abdominal surgical problems, either with intra-abdominal opportunistic infection as a result of their immunosuppression, or with associated malignancies. We report a 39-year-old man who developed intermittent nausea and vomiting, which was originally thought to be a side-effect of the chemotherapy he was receiving for facial Kaposi's sarcoma. However, he was found to have intraperitoneal Kaposi's sarcoma causing small bowel obstruction, which was successfully excised at laparotomy. There were no perioperative complications despite AIDS-related respiratory disease. The patient remained free of abdominal symptoms until his death. HIV infections or AIDS alone should not be contraindications to surgery for such problems, as careful patient selection can yield good results and significantly improve quality of life.
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PMID:Palliative surgery for acute bowel obstruction caused by Kaposi's sarcoma in a patient with AIDS. 1280 Apr 71

Lactic acidosis is an uncommon but potentially life-threatening adverse effect of didanosine. When given concomitantly with tenofovir disoproxil fumarate (DF), the area under the concentration-time curve of didanosine is increased by 48-60%. A 63-year-old man with human immunodeficiency virus (HIV) infection tolerated several didanosine-containing antiretroviral regimens. He developed generalized weakness, loss of appetite, weight loss, nausea, and vomiting 1.5 years after tenofovir DF was added to his didanosine-containing regimen. He was diagnosed with lactic acidosis and died after a 13-day hospital stay, when his lactate level increased to 189.7 mg/dl and his arterial blood gas pH value fell to 6.75. Health care providers should maintain a high index of suspicion for lactic acidosis in patients with HIV infection who receive didanosine and tenofovir DF concurrently. For patients receiving antiretroviral regimens containing this drug combination, it would be prudent to monitor lactate levels periodically. This is especially important when patients experience symptoms suggestive of lactic acidosis, such as weakness, abdominal pain, weight loss, nausea and vomiting, and shortness of breath.
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PMID:Fatal lactic acidosis associated with coadministration of didanosine and tenofovir disoproxil fumarate. 1533 57


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