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M Opravil

Publications and source records attributed to M Opravil.

At least 73 records · Page 4Linked to original sources
PubMed1997

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

HIV Infections↗
PubMed1997

Cytomegalovirus retinitis: decreased risk of bilaterality with increased use of systemic treatment. Swiss HIV Cohort Study Group.

Cytomegalovirus (CMV) retinitis may be treated systemically or intravitreally. We reviewed retrospectively patients with CMV retinitis, in order to determine whether systemic treatment was associated with less spread of CMV retinitis from one eye to the other. Of 222 cases, 92 patients had bilateral disease at onset of CMV retinitis, leaving 130 for analysis. Bilaterality occurred in 10 patients during 12,687 days of systemic treatment and in 34 during 14,791 days without systemic treatment (odds ratio [OR] = 2.92; confidence interval [CI], 1.44-5.90). Patients who had received systemic treatment for <50% of the follow-up period had a greater risk of bilaterality (OR = 3.7; CI, 2.79-4.54) than did the more intensively treated patients. CD4 cell levels also contributed to increased risk, but multivariate analysis showed that CD4 cell counts and treatment intensity were independent risk factors. CMV retinitis was more likely to become bilateral in patients who received less intravenous therapy. Local treatment can complete but does not replace systemically administered therapy.

Adult↗
PubMed1997

Simple monitoring of antiretroviral therapy with a signal-amplification-boosted HIV-1 p24 antigen assay with heat-denatured plasma.

OBJECTIVE: Virus load determination has become indispensable for the management of HIV patients, but depends on expensive assays of a low throughput. We evaluated whether a highly improved HIV-1 p24 antigen detection procedure which involves heat-mediated immune complex dissociation and signal-amplification-boosted enzyme-linked immunosorbent assay (ELISA) was suitable for antiretroviral treatment monitoring. DESIGN AND METHODS: Virus load in plasma was determined for 127 plasma samples taken at 0, 2, 6, 12, 18, 24, 30 and 36 weeks from 23 patients with CD4+ T cells < 50 x 10(6)/l who received indinavir 800 mg three times daily in addition to prior antiretroviral treatment. Tests included polymerase chain reaction (PCR) for viral RNA, measured prospectively with the Roche Amplicor kit, and retrospective batch testing of heat-denatured samples for p24 antigen by the DuPont HIV-1 p24 Core Profile ELISA linked with a tyramide signal amplification step. Particle-associated reverse transcriptase (RT) by the product-enhanced RT (PERT) assay was determined as an independent third-opinion viral load marker. RESULTS: p24 antigen was detected as sensitively as viral RNA. Overall detection during a median observation time of 25 weeks (range, 0-39) amounted to 75.6% for antigen and 73.6% for RNA. The antigen detection limit was 0.2 pg/ml. Antigen was detectable in all 23 baseline samples, whereas RNA was undetectable in one. Antigen and RNA levels in 79 samples positive for both markers correlated with r = 0.714 (P < 0.0001). Average changes in levels of p24 antigen and RNA at eight timepoints correlated with r = 0.982 (P < 0.0001). In individual patients, the two parameters behaved similarly, and in certain cases virtually identically. RT activity was measurable in all samples. CONCLUSIONS: The performance of this antigen detection procedure is comparable to RNA PCR, thus providing a simple, high throughput alternative in monitoring the efficacy of antiretroviral treatment.

Adult↗
PubMed1997

Are immunological markers, social and personal resources, or a complaint-free state predictors of progression among HIV-infected patients?

Predictors of disease progression were studied in 89 asymptomatic HIV-infected patients who were prospectively evaluated for psychosocial variables and the development of clinical symptoms over a period of 2 years. The subjects were assessed for symptoms, laboratory measures, demographic variables, social and personal resources, mental status, alcohol, nicotine and drug use, sexual activity and risk behaviour, and sexually transmitted diseases. After 1 year, 17% of the patients had developed HIV-associated symptoms (symptomatic disease or AIDS), and after 2 years, 32% had developed symptoms or had died. In the multivariate analyses, the baseline CD4 count was the only significant predictor of disease progression during both observation periods. Psychosocial measures did not predict the progression of HIV infection.

Adaptation, Psychological↗
PubMed1997

Indinavir urinary stones as origin of upper urinary tract obstruction.

The development of HIV protease inhibitors has dramatically improved the treatment prognosis of HIV-infected patients. The treatment, however, is associated with the potential for adverse events that are unique to protease inhibitors. One of them, Indinavir, can lead to the development of urinary stones. Three weeks after starting treatment with Indinavir, Zidovudine and Lamivudine, a 66-year-old patient developed symptomatic hydronephrosis on the right side due to multiple Indinavir stones blocking the ureter. Microhematuria and characteristic crystals were found in the urine. After interruption of treatment and increased fluid intake, the crystallurea was not longer detectable and the patient became asymptomatic within 3 days. Nephrostomy and ureteral stent placement were not necessary. Patients on treatment with Indinavir are required to maintain a fluid intake of at least 1.5-2 l/day to reduce the risk of crystallization and urinary stones. Pharmacologic metaphylaxis to prevent crystallization is not recommended.

Aged↗
PubMed1997

HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study.

To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.

Adult↗
PubMed1996

[Are there factors which maintain a subjective symptom-free psychological state? A study exemplified with HIV-infected subjects].

AIMS: In the absence of curative treatment, the diagnosis of HIV infection imposes a heavy burden. Infected persons are therefore confronted with psychological, social and physical problems and cope with them via different strategies and social resources. We investigated the question of what factors help to maintain a psychologically symptom-free state. METHODS: A sample of 117 asymptomatic HIV-infected persons was recruited out of the Swiss HIV Cohort Study (Part A) in 1989 and 1990. The psychological symptoms were assessed with a self-rating questionnaire (SCL-90-R). The structured interview focused on social network, social support (SONET), and coping strategies (FEKB). RESULTS: 79% of the asymptomatic persons did not report psychological symptoms. In multivariate analyses, "rumination" (= preoccupational thinking), female gender, and affectively negative relationships correlated with more, but affectively positive relationships and the strategy "defence against threat" with fewer, psychological symptoms. Additionally, there was no significant correlation between the immunological markers (CD4-, CD8-cell count, p24 antigen) and psychological complaints. CONCLUSIONS: The low number of asymptomatic HIV-infected persons with psychological symptoms (21%) is in accordance with other studies. Psychological symptoms and rumination correlate significantly in our sample. As rumination is difficult to recognize, HIV-infected patients should be directly questioned about rumination and their defence against threat should be supported in order to prevent the development of psychological symptoms.

Adaptation, Psychological↗
PubMed1996

Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS.

The aim of this double-blind, randomized, placebo-controlled, 12-week study was to assess the efficacy of rifabutin (450 or 600 mg/d) in the treatment of disseminated nontuberculous mycobacterial infection in patients with AIDS. Companion drugs in both arms of the study were ethambutol, clofazimine, and isoniazid. Because of low accrual, the study was prematurely terminated when a total of 382 patients had been enrolled, of which 200 were eligible (i.e., their specimens were culture-positive for Mycobacterium avium complex [MAC] or Mycobacterium xenopi at baseline) and 102 were evaluable (i.e., they were eligible, were treated for a minimum of 6 weeks, and had at least one culture assessment after baseline). The original protocol called for a total of 220 evaluable patients. At week 12, rifabutin treatment was associated with higher, although nonsignificant, rates of bacteriologic conversion than was the placebo arm, with regard to both the eligible patients (25% vs. 18%) and the evaluable patients (45% vs. 38%). Corresponding median times to culture conversion were 42 vs. 63 days (eligible patients) and 43 vs. 69 days (evaluable patients). No significant difference was observed in clinical improvement, mortality, or toxicity between the two treatment arms. The addition of rifabutin to a triple-drug regimen may contribute to the clearance of disseminated MAC infection in patients with AIDS, without causing additional toxicity.

AIDS-Related Opportunistic Infections↗
PubMed1996

[The role of aminoglycosides in HIV-infected patients].

The frequency of serious infections due to Pseudomonas aeruginosa is increasing among patients with advanced HIV infection; most of the cases are community-acquired. Early diagnosis and adequate treatment--usually with the combination of an anti-pseudomonas beta-lactam antibiotic and an aminoglycoside--have a crucial bearing on prognosis. The good in vitro activity of aminoglycosides against mycobacteria contrasts with the need for intravenous administration and toxicity. In patients with Mycobacterium avium complex infection, amikacin should be given only in the event of difficulty with an oral regimen and only on a temporary basis. Similar rules apply to the treatment of multiresistant tuberculosis with streptomycin or amikacin. Paromomycin is not absorbed by the gastrointestinal tract when taken orally, constitutes the treatment of choice against cryptosporidiosis and serves as an alternative against Entamoeba histolytica and Giardia lamblia. Topical treatment with paromomycin ointment can be used in cutaneous leishmaniasis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Clinical and epidemiologic features of infection with Mycobacterium genavense. Swiss HIV Cohort Study.

OBJECTIVES: To characterize clinical and epidemiologic features of infections with Mycobacterium genavense. DESIGN: Case series and case-control studies. Patients with M genavense were compared with two control groups: CD4 controls were matched on the basis of CD4 counts, and Mycobacterium avium-intracellulare complex controls had disseminated infection with M avium-intracellulare complex. RESULTS: Fifty-four patients with disseminated infections caused by M genavense were found, from Europe (37), North America (15), and Australia (two). All were infected with human immunodeficiency virus. The median CD4 count was 0.016 x 10(9)/L (16/mm3) (range, 0.001 to 0.082 x 10(9)/L). Eighty-seven percent had fever and weight loss, 44% had diarrhea, 43% had splenomegaly, 39% had hepatomegaly, and 72% had anemia. In Swiss university hospitals, M genavense was responsible for 12.8% of nontuberculous disseminated mycobacterial infections in patients with human immunodeficiency virus from 1990 to 1992. The median survival was 190 days after the first isolation of M genavense. Among the patients who had been treated with at least two antimycobacterial drugs for 1 month or more, median survival was 263 days (95% confidence interval, 144 to 382 days), compared with 81 days (95% confidence interval, 73 to 89 days) for those not treated (P = .0009). Survival in patients with M genavense was similar to the survival of M avium-intracellulare complex controls. However, patients with similar CD4 counts (CD4 controls) survived longer (median, 342 days; 95% confidence interval, 269 to 415 days; P < .0003). CONCLUSIONS: Infection with M genavense may be responsible for more than 10% of disseminated nontuberculous mycobacterial infections in patients with human immunodeficiency virus infection. Its clinical presentation and response to treatment are similar to those of infection with M avium-intracellulare complex.

AIDS-Related Opportunistic Infections↗
PubMed1995

Dapsone/pyrimethamine may prevent mycobacterial disease in immunosuppressed patients infected with the human immunodeficiency virus.

Dapsone exhibits activity against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) in vitro. We retrospectively examined the incidence of mycobacterial diseases within a randomized prospective trial of prophylaxis for Pneumocystis carinii pneumonia and toxoplasmosis. Of 501 participants who had not previously had a mycobacterial disease, 274 received dapsone/pyrimethamine (200/75 mg once weekly) and 227 received aerosolized pentamidine (300 mg once every 4 weeks). The median CD4 lymphocyte count was 113/microL, and the median duration of treatment was 369 days. Six cases of tuberculosis, 22 of MAC infection, and 3 of Mycobacterium genavense disease occurred during treatment. Stratified by basement CD4 lymphocyte counts, the annual product-limit incidence of mycobacterial disease was 5% during treatment with dapsone/pyrimethamine vs. 12% during treatment with aerosolized pentamidine for patients whose counts were 0-24/microL, 0 vs. 12% for those whose counts were 25-49/microL, and 7% vs. 9% for those whose counts were 50-99/microL. Adjusted for CD4 lymphocyte counts at start of treatment, the relative risk for patients receiving dapsone/pyrimethamine was 0.47 (95% confidence interval, 0.19-1.16; P = .10). This inexpensive and simple regimen may prevent mycobacterial diseases and warrants further investigation as a means of prophylaxis for multiple opportunistic diseases.

Adult↗
PubMed1995

Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.

To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.

AIDS-Related Opportunistic Infections↗
PubMed1995

Monitoring of co-trimoxazole concentrations in serum during treatment of pneumocystis carinii pneumonia.

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

AIDS-Related Complex↗
PubMed1994

[Sputum examination in the diagnosis of Pneumocystis carinii pneumonia in HIV-infected patients].

To assess the sensitivity and negative predictive value of sputum examination for Pneumocystis carinii in HIV-positive patients, follow-ups were performed in HIV-infected patients who had been investigated for the presence of Pneumocystis carinii (376 examinations of sputum and 71 bronchoalveolar lavages). Pneumocystis carinii pneumonia was diagnosed 65 times in 64 patients (57 male and 7 female, median age 35 [23-67]years). In 52% of the cases (n = 34) the pathogen was identified in the sputum, in 48% (n = 31) by means of the bronchoalveolar lavage. Of 342 negative findings in sputum examination, five were definitely false negative since the subsequent lavage yielded pneumocysts. In nine further cases Pneumocystis carinii pneumonia could not be excluded because of the course of the disease. In patients from whom sputum samples were available the sensitivity of pathogen identification was at least 70.8% and the negative predictive value at least 95.9%. Since preceding prophylaxis did not render identification in the sputum more difficult, examination of spontaneous or provoked sputum is indicated as a first hand measure in all patients infected with HIV in whom Pneumocystis carinii pneumonia is suspected.

AIDS-Related Opportunistic Infections↗
PubMed1994

Infectious complications in 100 consecutive heart transplant recipients.

Clinical and laboratory data on infectious complications in 100 consecutive heart transplant recipients were analyzed retrospectively. The mean length of follow-up was 651 +/- 466 days. All patients received a basic immunosuppressive regimen including cyclosporine (whole blood target trough level 400-600 micrograms/l), azathioprine (1 mg/kg/day) and prednisone (0.15 mg/kg/day). Early rejection prophylaxis consisted of polyclonal rabbit antithymocyte globulin (ATG) (4 mg/kg/day for 4 days) in the first 57 patients and monoclonal murine OKT-3 (5 mg/day for 14 days) in the remaining patients. The primary cause of death was infection in three patients and rejection in 16 (p < 0.001). The incidence of infection was 0.96/patient/year (n = 179); 95 infections were nosocomial (53%), 47 community-acquired (26%) and 37 opportunistic (21%). The number of hospitalizations due to infections was fewer than that due to rejection (53 versus 246 respectively, p < 0.0001), but the mean length of hospital stay was longer in the first group (13.85 +/- 10.92 days versus 3.48 +/- 2.28 days, p < 0.001). Previous early rejection prophylaxis with OKT-3 was associated with a greater number of opportunistic and nosocomial infections compared to prophylaxis with ATG (p < 0.05), as was treatment with ATG and steroid pulses compared to steroid pulses alone in cases of opportunistic infection (p < 0.05).

Adult↗
PubMed1994

Nontoxigenic Corynebacterium diphtheriae isolated from intravenous drug users.

During a prospective study 117 intravenous drug users were screened for infection with Corynebacterium diphtheriae. Nontoxigenic C. diphtheriae was found in 5 of 132 throat swab specimens and in 5 of 28 skin ulcer specimens taken from July 1991 to April 1992. When phenotypic and molecular typing methods were used, these 10 strains were shown to belong to a single clone. During the same period no strain was isolated from 200 controls. Clinical manifestations of infection were not clearly attributable to C. diphtheriae--no typical membranous pharyngitis was present. The presence of a single clone among homeless intravenous drug users in Zurich indicates the presence of C. diphtheriae in parts of the population with poor standards of hygiene and low socioeconomic status.

Adult↗