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Biomedical subjects

J Ruedy

Publications and source records attributed to J Ruedy.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of zidovudine resistant variants of HIV-1 isolated from patients on prolonged therapy.

As part of a clinical trial to assess zidovudine related toxic effects, the authors followed 48 initially asymptomatic individuals who received prolonged therapy with this drug at several tertiary care institutions. Blood samples had been obtained for viral isolation every three months and had yielded infectious HIV-1 progeny in over 94 percent of cases. After one year of therapy, over 30 percent of individuals had developed variants of HIV-1 that displayed in vitro resistance to zidovudine. Six of these zidovudine resistant variants of HIV-1 were compared with drug sensitive isolates obtained from the same subjects prior to initiation of treatment. The drug resistant variants were generally as infectious per mg viral protein for both susceptible T cell lines and peripheral blood mononuclear cells as the corresponding parental isolates from which they were derived. The drug resistance phenotype remained stable, in that zidovudine-insensitive species could still be identified, following many replication cycles in the absence of drug pressure. However, the percentage of zidovudine resistant viruses appeared to diminish in culture over time under such conditions. This was demonstrated by the fact that lower percentages of cells became infected in the presence of the drug, if the viruses used for infection had been propagated in the absence of the drug. In addition, higher concentrations of such viruses were required to initiate infection in the presence of the drug, and these viruses possessed lower IC50's for zidovudine. This suggests that zidovudine resistant variants of HIV-1 may be unlikely to possess any growth advantage in the absence of the drug.

Blotting, Southern↗
PubMed1991

Aerosol pentamidine-induced bronchoconstriction. Predictive factors and preventive therapy.

OBJECTIVE: To describe the frequency of aerosol pentamidine-induced bronchoconstriction, its relationship to non-specific airway responsiveness, and its response to preventive therapy using salbutamol, ipratropium bromide, or sodium cromoglycate. METHODS: Consecutive HIV-infected individuals starting prophylactic AP were eligible if they had not been previously treated with this agent. Simple spirometry was performed before and 10 min after a single 60-mg dose given through an ultrasonic nebulizer. Methacholine challenge was performed in all subjects 24 h to four days after the initial AP dose. Subjects with a change in FEV1 (delta FEV1) greater than or equal to 10 percent decrease after the initial AP dose were restudied on three separate occasions (greater than 24 hours apart) after premedication with two puffs of salbutamol (200 micrograms), ipratropium bromide (40 micrograms), or sodium cromoglycate (2 mg), in random order. RESULTS: Fifty-three subjects were studied. The median delta FEV1 after a single dose of AP was -7.0 percent (range: -47 percent, 1.8 percent). The delta FEV1 following AP was only partially predicted by the degree of nonspecific bronchial responsiveness as measured by a standard methacholine challenge. Age, current smoking, history of asthma, baseline FEV1, or a prior episode of PCP failed to predict the delta FEV1 following AP. Eighteen subjects (34 percent) had a delta FEV1 greater than or equal to 10 percent decrease (median: -17.0 percent). In these subjects, after premedication with salbutamol, ipratropium bromide, and sodium cromoglycate, the median delta FEV1 was 1.0, 0.8, and -9.6 percent, respectively. CONCLUSION: Aerosol pentamidine produced a decrease in FEV1 greater than or equal to 10 percent in 34 percent of subjects. This was not accurately predicted by the methacholine response. The bronchoconstriction induced by AP was effectively prevented by either salbutamol or ipratropium, whereas cromoglycate was only partially effective.

Adult↗
PubMed1991

Canadian multicenter azidothymidine trial: AZT pharmacokinetics.

The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HIV)-infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV-infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) +/- SD, 9.9 +/- 5.7 microM.h, maximum concentration (Cmax) +/- SD, 7.3 +/- 4.7 microM; time to maximum concentration (Tmax) +/- SD, 0.93 +/- 0.42 h, and half-life (t1/2) +/- SD, 1.0 +/- 0.8 h. Corresponding values for GAZT were: AUC +/- SD 35.7 +/- 10.3 microM.h, Cmax +/- SD 21.3 +/- 7.3 microM, Tmax +/- SD 1.2 +/- 0.50 h, t1/2 +/- SD 0.98 +/- 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier Cmax for AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomatic HIV disease when compared with previous reports in patients with later disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Corticosteroids prevent early deterioration in patients with moderately severe Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS)

OBJECTIVE: To determine whether oral corticosteroids can prevent early deterioration in patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. METHODS: Included patients were having their first P. carinii pneumonia episode, had no other known active pulmonary pathology, had no contraindications for corticosteroids, received no anti-P. carinii pneumonia medications for more than 48 hours, and had oxygen saturation by pulse oximetry of 85% or more and less than 90% at rest or a 5-percentage-point decrease in oxygen saturation with exercise while breathing room air. Consenting subjects were randomly assigned to prednisone, 60 mg/d for 7 days, followed by a progressive tapering over 14 days or to an identical placebo. Early deterioration, the endpoint of the trial, was defined as a 10% decrease in baseline oxygen saturation on day 3 or thereafter. The cases of patients developing early deterioration were considered to be failures of treatment; the code was then broken, and the patient's treatment was left to the judgment of the treating physician. Sequential analysis was done with the primary variable being development of early deterioration. RESULTS: The trial was terminated 5 April 1989 on the basis of the sequential analysis when a total of nine episodes of early deterioration had occurred in the first 37 patients at an overall significance level of P = 0.0136. A total of 8 of 19 placebo-treated patients (42.1%) developed early deterioration compared with only 1 of 18 patients (5.6%) treated with corticosteroids. Baseline characteristics were not statistically different between the two treatment groups. The adjusted odds ratio for the treatment effect was 5.87 (95% CI, 1.27 to 27.4). The adjusted point estimates for the probability of early deterioration in the placebo and corticosteroid groups were 43% and 12%, respectively. All 8 patients in the placebo group developing early deterioration recovered rapidly with addition of corticosteroid treatment. The single patient with early deterioration in the corticosteroid group died on day 6 from overwhelming P. carinii pneumonia, as documented at autopsy. The corticosteroid group had an increased exercise tolerance on day 7 that persisted at day 30. CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with moderately severe AIDS-related P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Validity and reproducibility of a screening examination for neurological abnormality in persons exposed to methylmercury.

The validity and reliability of methods of screening for neurologic abnormality were assessed as part of an investigation of an outbreak of methylmercury exposure in two northern Canadian communities. Four hundred and forty-five Cree Indians were examined by one of five neurologists in a complete neurologic examination and by a trained paramedical observer in a short screening examination which included a selection of tests from the complete examination. The screening examinations were recorded on videotape and those for 176 men were reviewed by the five neurologists and the paramedical observer 1 year after the field studies. The prevalence of abnormality assessed in the field screening examination was greater than that assessed during the complete neurologic examination, for neurologic features included in both examinations. However, agreement between examinations in identifying individuals with abnormality was poor with the sensitivity of the screening examination falling under 50% for half of the neurologic features examined. In contrast, specificity was over 80% for 14 of 18 features. Review of the videotapes revealed marked interobserver variation in the assessment of the prevalence of neurologic abnormality and poor agreement with the neurologic examinations in the identification of abnormality in individuals, with kappa less than 0.2 for most neurologic features. The levels of agreement between the neurologic examinations and the screening examinations conducted in the field and by videotape review suggest that neither screening examination provides equivalent information in the identification of the presence of abnormality to that obtained in the neurologic examination.

Female↗
PubMed1990

Pathologic dependence of oxygen consumption on oxygen delivery in acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.

Oxygen consumption is pathologically dependent on oxygen delivery in ARDS and sepsis. We asked whether oxygen consumption is dependent on oxygen delivery in severe acute respiratory failure secondary to AIDS-related PCP. In five patients who had AIDS-related PCP, diffuse bilateral pulmonary infiltrates, no evidence of bacterial infection, and acute respiratory failure requiring mechanical ventilation with arterial oxygen tensions less than 75 mm Hg while breathing at least 50 percent oxygen, and PEEP greater than 10 cm H2O, we determined oxygen delivery and consumption by calculation from thermodilution cardiac output and arterial and mixed venous oxygen contents. Oxygen delivery was increased using transfusion of two units of packed red blood cells over one hour. Oxygen delivery increased 22 percent (638 +/- 204 to 778 +/- 201 ml/min.m2, p less than or equal to 0.006). Oxygen consumption increased 11 percent (134 +/- 34 to 149 +/- 29 ml/min.m2, p less than or equal to 0.02). The oxygen extraction ratio did not change. We conclude that similar to ARDS and sepsis, oxygen consumption may be pathologically dependent on oxygen delivery in patients who have severe acute respiratory failure secondary to AIDS-related PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The effect of zidovudine on platelet count in HIV-infected individuals.

Seventy-four HIV-infected homosexual males belonging to CDC groups IIB, III, and IVC2 were treated with increasing doses of zidovudine within the Multicentre Canadian AZT Trial. Following a 3 week observation period, consenting volunteers received 600 mg/day for 18 weeks, 900 mg/day for 9 weeks, and 1,200 mg/day for 9 weeks. This was followed by a 6 week washout period after which zidovudine was restarted at 1,200 mg/day for 18 weeks. Patients were followed for a total of 63 weeks. Every 3 weeks they underwent a full clinical and laboratory assessment. For the purpose of this analysis, subjects were divided according to the mean initial platelet value (greater than or equal to 150,000 or less than 150,000/L) into normals (n = 57) and thrombocytopenics (n = 12), respectively. Analysis of variance was used to compare the mean platelet values at each zidovudine dose. All comparisons were made against baseline values. Zidovudine increased platelet counts in normal and thrombocytopenic subjects. The magnitude of this effect varied depending on the baseline platelet count. Among normals, the platelet count increased from 241,000 +/- 45,000/L at baseline to 261,000 +/- 51,000/L (p less than 0.01). while receiving 600 mg/day of zidovudine. This effect was self-limited, reaching a peak by week 3. The platelet count decreased to baseline values despite increasing the dose of zidovudine to 900 or 1,200 mg/day. The platelet count further decreased to 218,000 +/- 43,000/L during the washout phase (washout vs. 1,200 mg, p less than 0.01).2+ not found to be dose related. The platelet count decreased to 101,000 +/- 34,000/L during the washout phase (washout vs. 1,200 mg/day, p less than 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗
PubMed1989

Acute respiratory failure secondary to Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A potential role for systemic corticosteroids.

Pneumocystis carinii pneumonia (PCP) remains the most frequent life-threatening complication of HIV infection. A retrospective study was undertaken in an attempt to establish the incidence of acute respiratory failure (ARF) in AIDS-related PCP, its mortality, and the impact of adjuvant systemic corticosteroids on its outcome. Of 127 AIDS-related PCP episodes diagnosed at St. Paul's Hospital between Jan 1, 1981, and March 31, 1987, 27 developed ARF (21 percent), and the 24 who consented to ICU admission for ventilatory support were reviewed. All were given IV pentamidine or trimethoprim-sulfamethoxazole or both sequentially. Overall mortality of ARF secondary to AIDS-related PCP was 50 percent. The use of adjuvant systemic corticosteroids was associated with a decreased mortality. Of the 18 patients treated with IV hydrocortisone (400 to 1,000 mg/day in divided doses for the duration of ARF followed by a tapering regimen over 10 to 15 days), seven (39 percent) died, while five of six (84 percent) treated without corticosteroids died (p = 0.05). Survivors received ventilation for 5 +/- 2 (mean +/- SD) days and all were discharged from hospital after 20 +/- 4 days. Survivors were also younger (34 +/- 8 vs 43 +/- 10 years, p = 0.034) and presented earlier (14 +/- 3 vs 34 +/- 7 days after onset of symptoms p = 0.017). Known AIDS, previous PCP episodes, and arterial blood gas values at the onset of ARF did not correlate with outcome. We conclude that ARF secondary to AIDS-related PCP merits aggressive management. In particular, younger patients presenting early after the onset of respiratory symptoms appear to have a better prognosis. The decreased mortality associated with the use of adjunctive corticosteroids supports the need for prospective controlled evaluation of this therapeutic modality.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A profile of academic physicians in British Columbia.

To determine the extent of involvement of British Columbia's physician community in the operation of the province's only medical school, the authors sent questionnaires to all physicians who had any affiliation with the University of British Columbia (UBC). About 20 percent of the province's physicians were involved in some capacity with the UBC Faculty of Medicine, which accepts about 120 students into the first year annually. Most faculty held "clinical" appointments, meaning that they pursued largely non-academic careers. Full-time academic appointees worked more than 20 percent more hours annually than did their "clinical" counterparts, and average hours for men exceeded those for women. As many as two-thirds of the full-time faculty were also engaged in sufficient clinical practice activity to be classified as full-time practicing physicians by a definition adopted by a provincial Joint Medical Manpower Committee.

Adult↗
PubMed1988

Clinical skills of medical residents: a review of physical examination.

Students are introduced to techniques of physical examination at medical school. However, their skills are deficient at the time of graduation, and with the increasing shift of clinical teaching away from the bedside and into the conference room it is expected that these skills will weaken in succeeding generations of physicians. A practical and satisfactory method of addressing this problem during internship and residency training has not been forthcoming because of the lack of a regular forum for the teaching of clinical skills in busy tertiary referral hospitals and the shortage of teachers with the necessary skills and commitment to teaching a large number of house staff. We describe a program whose unique hierarchical approach has permitted a detailed ongoing review of physical examination. One clinician was able to teach 24 residents by instructing a small group of senior residents, who in turn, after practising with clinical clerks, taught groups of junior residents.

Clinical Clerkship↗
PubMed1987

Intraoperative cyanosis: a case of dapsone-induced methaemoglobinaemia.

Intraoperative cyanosis is most commonly caused by hypoxaemia. The anaesthetist is required to perform a rapid series of diagnostic manoeuvres and take remedial action. Occasionally methaemoglobin, sulfhaemoglobin, or haemoglobin M, undetected preoperatively, is the cause of the cyanosis. We report a case of methaemoglobinaemia secondary to dapsone ingestion that was diagnosed intraoperatively. Dapsone, a sulfone, is used therapeutically to treat leprosy and dermatitis herpetiformis. The differential diagnosis of cyanosis, and the origin and fate of methaemoglobin are discussed. In addition the diagnostic steps and the laboratory investigations required to make the diagnosis are listed.

Adolescent↗
PubMed1987

Therapeutic implications of sodium abnormalities in hypertension.

Abnormalities in cellular sodium transport have been demonstrated in leukocytes and erythrocytes of some patients with essential hypertension. Some patients with essential hypertension retain more sodium on a high-salt diet, despite an accompanying increase in pressure. Some epidemiological studies suggest a relationship between dietary sodium intake and essential hypertension. The biological significance of these findings remains uncertain. There is too little evidence to support dietary sodium restriction as a primary preventive measure in essential hypertension. Restriction of dietary intake of sodium to 80 mmol/day results in a reduction in blood pressure in a minority of patients with essential hypertension.

Aging↗
PubMed1985

Treatment of Pseudomonas and Serratia infections with ceftazidime.

The effectiveness and safety of parenterally administered ceftazidime were assessed in 20 patients with infections caused by Pseudomonas aeruginosa or Serratia marcescens. There were six infections involving the urinary tract, six wound infections, one respiratory tract infection, three septicaemias, one empyema, one mastoiditis and two infections of the epididymis. Sixteen of the isolates were resistant to at least one aminoglycoside antibiotic. Fifteen patients were clinically and bacteriologically cured, two patients improved, but had relapses and three patients showed no response. The lack of clinical response was due to the development of resistance by P. aeruginosa in two patients with osteomyelitis, one of whom also had diabetes mellitus. The third patient who had chronic lymphocytic leukaemia developed post-operative osteomyelitis and septicaemia with serratia. She did not respond to treatment. Side effects consisted of a positive direct Coomb's test without evidence of haemolysis in two patients and a mild maculopapular rash in one patient.

Adult↗
PubMed1979

Antihypertensive efficacy of propranolol given twice daily.

The therapeutic efficacy of propranolol in four and two daily doses was compared in 63 treated hypertensive patients in a multicentre trial. After 3 months of a stable diastolic blood pressure while receiving propranolol four times a day the patients were switched to a twice-a-day regimen, the drug being given at 8 am and 8 pm, with the same total daily dose, for 3 more months. Blood pressures and heart rates were measured at 8 am, 12 noon, 4 pm and 8 pm at 4-week intervals. There were no significant changes in mean blood pressure after the change to the twice-a-day regimen, although some patients reported new side effects. Compliance appeared to be unaffected.

Adolescent↗