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Biomedical subjects

M Opravil

Publications and source records attributed to M Opravil.

108 records · Page 6Linked to original sources
PubMed1991

Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma.

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia.

BACKGROUND: Current recommendations for prophylaxis of Pneumocystis carinii pneumonia (PCP) are based on data from patients who have had at least one episode of PCP (secondary prevention). We designed a study to determine the efficacy and side effects of inhaled pentamidine in the primary prevention of PCP. METHODS: Two hundred twenty-three patients sero-positive for human immunodeficiency virus (HIV) who had the acquired immunodeficiency syndrome (AIDS) but not PCP, who had advanced AIDS-related complex, or who had less than 0.2 x 10(9) CD4-positive lymphocytes per liter received either 300 mg of pentamidine isethionate or 300 mg of sodium isethionate every 28 days by inhaler. The proportion of patients surviving without PCP was analyzed with the log-rank test as a function of time spent in the trial, according to the intention to treat with either placebo or pentamidine. RESULTS: The third of five planned interim analyses showed a significant difference in the occurrence of PCP, with 8 cases in pentamidine group and 23 in the placebo group (nominal P value = 0.0021). There were no deaths within 60 days of the diagnosis of PCP and no significant differences in survival between groups. Approximately 53 inhalations were needed to prevent one episode of pneumonia. Thirty-eight of 114 patients given pentamidine (33 percent) and 7 of 109 given placebo (6 percent) had moderate-to-severe coughing during inhalations (two-tailed P less than 0.00001), which caused 4 patients given pentamidine (3.5 percent) to discontinue taking it. CONCLUSIONS: A dose of 300 mg of aerosolized pentamidine given every four weeks was well tolerated and 60 to 70 percent effective in preventing a first episode of PCP in patients with HIV infection.

AIDS-Related Complex↗
PubMed1991

Poor antibody response after tetanus and pneumococcal vaccination in immunocompromised, HIV-infected patients.

Ten patients with symptomatic HIV infection (six with ARC, four with AIDS) received tetanus and 23-valent pneumococcal vaccination. Anti-tetanus IgG and IgM, and anti-pneumococcal IgG against all 23 capsular types of the vaccine were measured on days 0, 11, 17, 30, and 90. Anti-pneumococcal IgG were simultaneously determined in two plasma pools of 100 healthy unimmunized blood donors and of 112 healthy adults who had previously received a 14-valent pneumococcal vaccination. Peak IgG responses to both vaccines were observed on day 17; thereafter, the antibody levels gradually fell again. Anti-tetanus IgG rose from 0.6 U/ml (geometric mean) to 2.0 U/ml on day 17. Anti-tetanus IgM remained unchanged. Anti-pneumococcal IgG increased only by 1.14-fold compared with pre-vaccination levels (geometric mean of IgG rises against all 23 polysaccharides in 10 patients), and exceeded the upper 95% limit of unvaccinated blood donors in only 30 out of 230 specimens. Pre-vaccination levels for pneumococcal type-specific IgG were significantly higher in HIV-infected patients compared with the pool of unimmunized healthy controls, possibly indicating a higher rate of previous pneumococcal infections in HIV-seropositive subjects. However, post-pneumococcal vaccination levels were significantly lower in HIV-infected patients than in the pool of healthy controls. The increase in anti-tetanus IgG significantly correlated with the level of CD4 lymphocytes and with in vitro lymphocyte proliferation by pokeweed mitogen (5 micrograms/ml) and phytohaemagglutinin (2.5 micrograms/ml), confirming a particularly low vaccination response in patients who were severely immunocompromised.

AIDS-Related Complex↗
PubMed1991

Primary pulmonary hypertension in HIV infection.

A prospective evaluation of 74 human immunodeficiency virus (HIV)-infected patients with cardiopulmonary complaints revealed six patients (8.1 percent) with pulmonary hypertension with elevated right ventricular systolic over right atrial pressure of 58 +/- 8 mm Hg (range, 49 to 66 mm Hg), as documented by Doppler echocardiography. A thromboembolic cause was excluded by normal lung perfusion scans. Electrocardiographic and roentgenographic features of pulmonary hypertension were present in five patients. Two patients died three and nine months after diagnosis of pulmonary hypertension. Autopsy revealed plexogenic pulmonary arteriopathy in both. The observation of six patients with primary pulmonary hypertension (PPH) in a cohort of 1,200 HIV-infected subjects corresponding to an incidence of 0.5 percent is striking and suggests a possible association of PPH with HIV infection.

Adult↗
PubMed1990

Progression of HIV infection in misusers of injected drugs who stop injecting or follow a programme of maintenance treatment with methadone.

OBJECTIVE: To see whether misusers of injected drugs who stop injecting or switch to a programme of maintenance treatment with methadone have a reduced risk of progression of HIV infection when compared with a group of persistent misusers. DESIGN: Observational cohort study in HIV seropositive subjects with a current or past history of misusing injected drugs. SETTING: HIV outpatient clinic at the University Hospital of Zurich, Switzerland. PATIENTS: 297 Current and former parenteral drug misusers (median age 27) with asymptomatic HIV infection. During the observation period 80 subjects adhered to a programme of maintenance treatment with methadone, 124 continued with parenteral drug misuse, and 93 former misusers remained free of illicit drugs. No antiretroviral treatment was given during the study. MAIN OUTCOME MEASURES: Probability of progression of HIV infection from asymptomatic to symptomatic (Centers for Disease Control stage IV) as calculated by life table analysis and compared in the three groups of patients by means of a log rank test, and predictors of disease progression as analysed with a Cox proportional hazards regression model. RESULTS: The 297 patients were followed up for a median of 16 months. The median duration of injecting drug misuse before enrollment was 7.1 years. There were no significant differences among the three groups with respect to CD4+ counts at the beginning of the study (median 0.44 x 10(9)/l). Life table analysis showed a significantly lower probability of progression of HIV disease in both the methadone treated group and former drug misusers than in persistent injecting drug misusers. Multivariate regression analysis showed a relative risk of progression of the disease of 1.78 (95% confidence interval 1.20 to 2.67; p less than 0.01) in persistent injecting drug misusers, 0.48 (0.29 to 0.77; p less than 0.01) in the methadone treated group, and 0.66 (0.41 to 1.06; p = 0.085) in former drug misusers. CONCLUSIONS: Stopping the misuse of injected drugs slows the progression of HIV disease in infected subjects. Drug treatment programmes are effective in secondary prevention of HIV associated morbidity.

Adult↗
PubMed1990

[Pneumocystis carinii pneumonia in HIV infection: better prognosis because of early diagnosis].

The clinical presentation of 60 consecutive Pneumocystis carinii pneumonias in 58 HIV-infected patients (48 men, 10 women, mean age 34 [22-53] years) was prospectively evaluated from April to August 1989 and compared with 60 consecutive P. carinii pneumonias in 59 HIV-infected patients (55 men, 4 women, mean age 37.5 [22-60] years) between 1981-88. Mortality rates within 14 days after diagnosis of P. carinii pneumonia were 50% (8 of 16 patients) until 1985, 20.5% (9 of 44) between 1986 and August 1988, and 1.7% (one of 60) in 1989. The degree of severity of the pneumonias at time of diagnosis was markedly lower in 1989, as shown by following parameters (averages of 1989, compared with averages of 1981-88): lactate dehydrogenase 540 (250-1419) U/l versus 680 (235-1920) U/l (not significant); alveolo-arterial difference of partial oxygen tension (pA-aO2) 22.9 (0.5-73.5) mmHg versus 39.7 (19-70) mmHg (P less than 0.001); score of radiological findings 1.4 (0-3) versus 2.7 (0-4) (P less than 0.001). In 1989, mainly clinical symptoms (dry cough: 57 of 60 cases, dyspnea: 44 of 60 cases, fever: 43 of 60 cases) initiated the diagnostic procedure: chest radiographs, lactate dehydrogenase and pA-aO2 were normal in 13, 25 and 33 episodes, respectively. The lower mortality rate of P. carinii pneumonia could not primarily be explained by therapeutical progress since the treatment of choice did not change fundamentally since 1981. Above all, early diagnosis fundamentally determined the probability of survival.

Adult↗
PubMed1990

Compliance and laboratory data predict relapse rate of Pneumocystis carinii pneumonia during prophylaxis with aerosol pentamidine.

We evaluated 43 AIDS patients on prophylaxis with aerosol pentamidine (60 mg biweekly) after Pneumocystis carinii pneumonia (PCP). The effects of patients' inhalation compliance and of laboratory data during the initial PCP on subsequent PCP relapses were assessed. After a median of 8 months (range, 2-21.5 months) on pentamidine prophylaxis, 13 patients suffered a PCP relapse. Six of them had missed at least one inhalation within the last month before the relapse. Two of these six relapses were fatal. The relapse occurrence was significantly associated with the percentage of missed inhalations. Additional significant associations were found between relapses, low levels of T4 lymphocytes, and elevated serum lactate dehydrogenase during the initial PCP episode (29 patients). Mean levels of T4 lymphocytes were 27/mm3 and 47/mm3 in patients with and without subsequent relapses, mean levels of lactate dehydrogenase were 692 U/L and 605 U/L, respectively. Multivariate Cox regression did not reveal further differences between patients with and without relapses. The increased relapse risk associated with poor inhalation compliance stresses the need for appropriate guidance and motivation of the patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Prognostic score for Pneumocystis carinii pneumonia.

Sixty episodes of Pneumocystis carinii pneumonia in 59 patients were evaluated for risk factors predicting fatal outcome within 14 days after bronchoscopy. We found significantly higher values for serum lactate dehydrogenase (p less than 0.001), alveolar-arterial oxygen difference (p less than 0.001) and percentage of bronchoalveolar lavage neutrophils (p less than 0.001) in patients dying within 14 days, but there was considerable overlap of these variables between the two groups. Using a score system combining the three parameters allowed however an excellent discrimination between the two groups.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Primary prevention of Pneumocystis carinii pneumonia by inhalation of pentamidine. Preliminary results from a placebo-controlled randomized trial. Swiss Group for Clinical Studies on AIDS.

Patients with AIDS but without pneumocystis carinii pneumonia, patients with advanced AIDS-related complex (ARC), and asymptomatic patients with less than 200 CD4-positive lymphocytes/mm3 were randomized to one of two groups: group I: Inhalation of 300 mg of pentamidine every 28 days; group II: Inhalation of placebo (300 mg of Na isethionate) every 28 days. From May to November 28, 1989, 160 patients have entered the trial. Inhalations were well tolerated, with only a 6% use of bronchodilators and a 15% incidence of cough. Until now five patients died, none of them drug related. So far, six patients have developed pneumocystis carinii pneumonia; four of these were on pentamidine, and two on placebo. Five of the six cases occurred before the second inhalation. Recruitment will continue until 250 patients are enrolled.

Administration, Inhalation↗
PubMed1986

Use of a counterpulsation balloon as a substitute for the pulmonic valve: a new application.

An inflatable, 3-ml balloon positioned within the distal right ventricular outflow tract was used to restore pulmonic valve function in 8 dogs that had undergone open-chest valvectomy. Balloon inflation and deflation were accomplished with a counterpulsation console. Valvectomy produced loss of the pulmonic incisura, a decrease in pulmonary artery diastolic pressure (PADP; mean +/- standard error) (9.5 +/- 1.3 versus 4.4 +/- 0.6 mm Hg, p less than 0.01), and an increase in pulmonary artery pulse pressure (PAPP) (8.6 +/- 0.7 versus 19.1 +/- 1.9 mm Hg, p less than 0.01) without significantly affecting forward cardiac output (CO) (1,750 +/- 110 versus 1,880 +/- 230 ml/min, p is not significant). Properly timed counterpulsation restored the pulmonic incisura, raised the PADP from 6.1 +/- 0.8 to 9.5 +/- 0.8 mm Hg (p less than 0.01), lowered the PAPP from 15.1 +/- 1.4 to 10.6 +/- 1.0 mm Hg (p less than 0.01), and raised the forward CO from 1,850 +/- 260 to 1,920 +/- 260 ml/min (p less than 0.01). The injection of glass beads, 40 to 150 microns in diameter, into the right ventricular outflow tract increased pulmonary vascular resistance from 383 +/- 87 to 730 +/- 150 dyne . sec cm-5 (p less than 0.05) and decreased forward CO from 1,850 +/- 260 to 1,570 +/- 230 ml/min (p less than 0.05). Following this injection, counterpulsation again restored the pulmonic incisura, raised the PADP from 9.3 +/- 1.4 to 16.0 +/- 1.8 mm Hg (p less than 0.01), lowered the PAPP from 25.0 +/- 2.5 to 18.2 +/- 2.5 mm Hg (p less than 0.01), and raised the forward CO from 1,570 +/- 230 to 1,720 +/- 220 ml/min (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Pulmonary artery balloon counterpulsation for right ventricular failure: I. Experimental results.

The effects of pulmonary artery balloon counterpulsation (PABC) as a circulatory assist for the failing right ventricle were investigated. Sixteen anesthetized dogs underwent instrumentation to measure cardiac output and to record pressures in both ventricles, the pulmonary artery, and the aorta. Autonomic control of the heart was surgically and pharmacologically ablated. A specially designed counterpulsation balloon was inserted through the right ventricular (RV) outflow tract into the pulmonary artery. Pulmonary hypertension, induced acutely by the microembolization of the pulmonary circulation with glass beads combined with infusion of serotonin, served as a model for development of acute RV failure. Immediate effects of PABC were investigated in 10 dogs during normal function and failure of the right ventricle at different levels of preload. After further embolization which caused progressive cardiogenic shock, the effects of 10 minutes of PABC, and of its withdrawal, were examined. In all cases, PABC immediately decreased RV preload and afterload. In the failing right ventricle, counterpulsation also significantly increased cardiac output. Progressive cardiogenic shock was successfully reversed by PABC; after 10 minutes of counterpulsation, increases in cardiac output (+53%), arterial pressure (+55%), and RV minute work (+62%) were observed, paralleled by a fall in RV preload (-22%). After PABC was discontinued, the circulatory status again began to deteriorate. We conclude that PABC effectively improves function of the failing right ventricle caused by acute pulmonary hypertension.

Animals↗
PubMed1984

Pulmonary artery balloon counterpulsation for right ventricular failure: II. Clinical experience.

The use of pulmonary artery balloon counterpulsation (PABC) provided immediate salvage following cardiac surgical procedures in 2 patients with biventricular failure in whom inotropic drugs and intraaortic balloon counterpulsation did not provide sufficient support to allow weaning from cardiopulmonary bypass. Although both patients eventually died, the hemodynamic effectiveness of PABC was documented. The various clinical settings for right ventricular as well as biventricular failure are reviewed, the currently available options for treatment are summarized, and the directions for future laboratory investigation and possible clinical applications are presented.

Aged↗
PubMedDate not supplied

Variability of serum concentrations of trimethoprim and sulfamethoxazole during high dose therapy.

Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment of Pneumocystis carinii pneumonia. Daily doses of 15-22 mg/kg trimethoprim and 75-110 mg/kg sulfamethoxazole were given every 6 h. Despite administration of a loading dose of twice the regular dose, serum trough concentrations continuously rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamethoxazole. After 4-6 days mean trough concentrations of trimethoprim and sulfamethoxazole were 7.7 +/- 3.0 and 198 +/- 74 mg/l, with individual values of < 4.6 and < 103 mg/l in two patients and > 11.4 and > 307 mg/l in two others. Patients treated orally or i.v. had similar serum levels. However, large interindividual variability was observed despite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxazole over several days of treatment.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Phase I/II vaccination study of recombinant peptide F46 corresponding to the HIV-1 transmembrane protein coupled with 2.4 dinitrophenyl (DNP) Ficoll.

In order to evaluate tolerance, toxicity, and in vivo antigenicity, 29 HIV-1-infected patients (eight with ARC and 21 with AIDS) were vaccinated with a synthetic peptide derived from the gp41 transmembrane protein of the HIV-1. This peptide had been coupled with 2.4 dinitrophenyl-Ficoll (F46), a T-cell independent adjuvant. The patients received a single intradeltoid injection of either 0.1 or 0.3 mg of F46. Five of the individuals with AIDS were boostered, four of them twice. Anti-F46 antibody titers were measured before vaccination, and on days 7, 14, 21, 28, 90, 180 and 270 after vaccination. Anti-F46 titers rose at least twofold over prestudy values in 10/21 individuals with AIDS and in 1/8 individuals with ARC at least once during the observation period. The overall response, however, consisted of only weak antibody production that was independent of the dose or patient characteristics. No signs of toxicity or of clinical progression related to the vaccination were observed in this phase I/II trial of a T-cell independent therapeutic vaccine.

AIDS Vaccines↗
PubMedDate not supplied

Native and prosthetic valve endocarditis caused by Rothia dentocariosa: diagnostic and therapeutic considerations.

Three cases, one each of native valve, prosthetic valve and composite graft endocarditis caused by Rothia dentocariosa are described. The first patient presented with multiple brain abscesses and severe congestive heart failure due to destructive endocarditis with large vegetations on the mitral valve. He died shortly after emergency valve replacement. Gram-positive coccoid rods were identified in the vegetations of the excised mitral valve. The second patient had a R. dentocariosa endocarditis of a prosthetic aortic valve that was treated empirically with netilmicin and teicoplanin, due to an allergy to penicillin. Both antibiotics were replaced according to susceptibility testing in vitro with rifampin and ciprofloxacin, and the endocarditis was cured within 9 weeks. The third patient presented with a circular root abscess of an aortic composite graft that was successfully treated with rifampin and ceftriaxone without surgery. All patients had extensive periodontal disease which was thought to be responsible for hematogenic spread and seeding of the microorganism. The microbiological identification and antibiotic resistance pattern of the isolates, as well as therapeutic implications are discussed.

Actinomycetales↗
PubMedDate not supplied

Epidemiological and clinical aspects of mycobacterial infections.

The incidence of tuberculosis in the developed countries has recently started to rise again due to increased migration, a higher rate of direct transmission of Mycobacterium tuberculosis, and co-infection with HIV. The impact of the latter on the pathogenesis and presentation of tuberculosis is summarised. Important measures to prevent the further spread of tuberculosis include rapid diagnosis, prompt isolation of infectious patients, adequate control of treatment compliance, as well as surveillance of local resistance patterns. Disease due to the Mycobacterium avium complex is more frequent among HIV-infected patients in Central Europe than tuberculosis, and its development in the presence of immune deficiency seems to be mainly the result of a new infection with this ubiquitous microorganism rather than the reactivation of a previously acquired infection. It has a significant impact on mortality. The diagnosis of Mycobacterium avium complex infection requires a high degree of conjecture because most of the symptoms are non-specific, such as fever, night sweats, weight loss and anaemia. Promptly initiated treatment significantly prolongs the survival time of those affected by comparison with untreated patients.

AIDS-Related Opportunistic Infections↗