Gene/Protein Disease Symptom Drug Enzyme Compound
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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease.
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PMID:[Evaluation of the pharmacovigilance follow-up of zidovudine]. 226 33

Malignant external otitis (MEO) is a disease of the external auditive channel (EAC) due to Pseudomonas aeruginosa which usually involves individuals with diabetes mellitus. It may result in the invasion of the cranial base with cranial neuropathy and a high mortality rate despite therapy. We report the clinical features, diagnostic procedures, evolution and therapy of 8 patients with MEO, seven of which had cranial neuropathy. All patients have diabetes except one who had acquired immunodeficiency syndrome. All had otalgia, otorrhea and headache lasting for several months. Six patients had homolateral (as related to the MEO) facial palsy. One patient with bilateral MEO developed bilateral facial palsy and lesion of the cranial nerves VI (unilaterally) and IX through XII (bilaterally). In all patients P. aeruginosa was cultured from the EAC exudate scintigraphy with 99Tc showed uptake at medium ear and mastoid level in all 8 patients, suggesting a possible osteomyelitis. Scintigraphy with 67Ga was positive in the 6 cases where it was carried out, showing uptake in the soft tissues of the cranial base. Computed tomography was carried out in 6 patients, and it was useful to define the anatomical extent of the disease. The patients received different therapeutic schedules, particularly the combination of a betalactamic and aminoglucoside antibiotics. Follow up was characterized by common recurrences, and one patient died. The importance of early diagnosis and treatment to prevent the extension and recurrence of MEO are discussed. Cranial neuropathy is considered as a poor prognostic finding.
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PMID:[Otitis externa maligna and cranial neuropathy]. 228 52

Two patients with acquired immune deficiency syndrome presented with headaches and fevers. A diagnosis of cryptococcal meningitis was made by lumbar puncture and elevated cryptococcal antigens. Complaints of decreased vision in both patients led to the diagnosis of optic disc edema and cryptococcal choroiditis with yellow-white choroidal infiltrates noted in both eyes of the two patients. Systemic treatment with amphotericin B and 5' flucytosine led to resolution of the choroidal infiltrates. Late visual acuity loss was believed to be secondary to optic atrophy.
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PMID:Cryptococcal choroiditis. 234 88

To determine the compliance and tolerance with zidovudine (azidothymidine or AZT) therapy among poor, minority, and intravenous drug-using patients, data were collected on all AIDS and ARC patients followed for at least 4 weeks in a New York City Human Immunodeficiency Virus clinic. Ninety-nine patients received zidovudine, of whom 75% were males, 92% were minorities, and 59% had a history of intravenous drug use. Of the 99 patients, 72 had AIDS and 27 had ARC with T-helper (CD4) lymphocytes less than or equal to 500 mm3. Eighty-seven of the 99 patients (88%) were compliant with zidovudine therapy. Fifty-seven percent of these had at least one adverse drug reaction requiring dose reduction (44%) or cessation (13%). Adverse reactions were similar to those reported in other populations with HIV-related illness, although headache and nausea were less common. Twenty opportunistic infections (OIs) or HIV-related malignancies occurred in 15 of 82 (18%) patients who were on zidovudine for at least 4 weeks (7.6 OIs/1,000 patient weeks). Seven of the 82 died (9%), compared to 9 of the 17 patients (53%) who did not complete 4 weeks of zidovudine therapy (p less than 0.05). There were no significant differences in any of these measures when intravenous drug users were compared with other risk groups. We conclude that zidovudine can be administered to intravenous drug users and others in an inner city clinic with acceptable compliance and tolerance.
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PMID:Zidovudine therapy in an inner city population. 238 64

Inpatient and community-based care can be complementary in relation to the management of HIV disease. Medical records from 200 inpatients of Chikankata Hospital near Lusaka, Zambia and 200 home based patients were examined and compared for the common symptoms of presentation of HIV disease, associated opportunistic infections, and treatment protocols. Drug costs of both groups were also compared. The most common respiratory symptoms in the 2 groups are cough, chest pains, weight loss, and hemoptysis. Treatment employed for these symptoms were cortimoxazole, penicillin V, erthromycin, and tetracycline. Acetyl saliclic acid and paracetamol were used for pain relief in both groups. Gastointestinal system symptoms for both groups were diarrhea, weight loss, abdominal pain, and vomiting. Cotrimoxazole and metronidazole were used in treating diarrhea. Additional treatment protocol for the 2 patient samples included oral rehydration therapy for dehydration, antacid or bismuth subsalicylate for diarrhea and enteritis, and mycostatin for oral candidiasis. Central nervous system symptomatology included headache, dementia, neckace, and lethargy. Chloramphenicol was employed in treating bacterial meningitis. Diazepam and chlorpromazine were effective for restless patients. Genito-urinary system symptomatology for the 2 groups included dysuria, genital ulcers, hematuria, viral warts, and buboes. Antibodies were used for sexually transmitted diseases and infections. Skin symptomatology included rash and dermatitis, herpes zoster, abscess, kaposi's sarcoma, ulcers, furunculosis, and discharging anal sinus. In treating these symptoms, hospital based care and home based care were similar. Overall, it was found that hospital treatment protocols were detailed, expensive, and time consuming. Furthermore, hospital treatment for HIV positive patients is more expensive than HIV negative patients; hospital costs for 50 HIV negative patients totaled US$415.94 compared to US$1204.98 HIV positive/PTB negative patients and US$1705.62 for HIV positive/PTB positive patients. Drug cost/patient admission is increased by 469% if HIV positive. (author's modified).
AIDS Care 1989
PMID:Clinical care as part of integrated AIDS management in a Zambian rural community. 248 94

The purine analog 2',3'-dideoxyinosine (ddI), which has anti-retroviral activity in vitro was administered for up to 42 weeks to 26 patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex (ARC). Ten of these individuals were AZT-intolerant. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid (CSF). Comparatively little evidence of an effect against human immunodeficiency virus (HIV) was seen at the lowest four doses. However, patients in the four highest dose groups (ddI at 1.6 milligrams per kilogram intravenously and then greater than or equal to 3.2 milligrams per kilogram orally at least every 12 hours or higher) had increases in their circulating CD4+ T cells (P less than 0.0005), increased CD4/CD8 T cell ratios (P less than 0.01), and, where evaluable, more than an 80% decrease in serum HIV p24 antigen (P less than 0.05). The patients also had evidence of improved immunologic function, had reduced viremic symptomatology, and gained a mean of 1.6 kilogram with these comparatively infrequent dosing schedules (every 8 or 12 hours). The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release) and mild headaches and insomnia. These results suggest that serious short-term toxicity at therapeutic doses is not an inherent feature in the profile of agents with clinical anti-HIV activity. Further controlled studies to define the safety and efficacy of this agent may be worth considering.
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PMID:In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine. 250 40

To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS 1989 Sep
PMID:Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial. 252 69

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.
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PMID:A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). 254 86

A series composed by 13 patients suffering Tuberculous Meningitis (TM) and Acquired Immunodeficiency Syndrome (AIDS) is reported. The characteristics of the disease are compared with those obtained from a control group. TM reached a frequency of 18% in the first 66 patients with AIDS and neurologic disorders attended by the authors. The male/female ratio was 12:1. There was lesser frequency of headache in the group with TM and AIDS, but there was a greater frequency of lymph nodes, anemia, leukopenia, hypergammaglobulinemia and elevated ESR that in the control group. These differences were statistically significative. Parabolic and hyperbolic correlations were found between the number of cells and the albumin or glucose concentration in the CSF (and also between the later two parameters) of the patients with TM and AIDS. The treatment was very efficacious, but the proper duration and the long-term results of the therapy are unknown due to the difficult follow-up.
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PMID:[Tuberculous meningitis and acquired immunodeficiency syndrome]. 263 55

Zidovudine (azidothymidine) is a thymidine analogue antiretroviral drug active against human immunodeficiency virus (HIV). In acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients, orally and intravenously administered zidovudine is effective in reducing the incidence of opportunistic infections and neoplasms, increasing helper T lymphocyte numbers, and improving survival rates and quality of life. Adverse effects include serious haematological abnormalities and severe headache, abdominal discomfort, nausea, myalgia and insomnia. In addition, neutropenia and other anaemias frequently limit zidovudine therapy and may result in a need for multiple blood transfusions, dose reductions or withdrawal of the drug. However, despite these problems and the lack of information about some aspects of zidovudine use, zidovudine provides a major hope for HIV-infected patients, and it has rapidly become the standard therapy for improving the quality and duration of the lives of AIDS and ARC patients.
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PMID:Zidovudine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. 266 Nov 94


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