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Biomedical subjects

J von Overbeck

Publications and source records attributed to J von Overbeck.

At least 19 recordsLinked to original sources
PubMed2005

Long-term survival and interruption of HAART in HIV-related pulmonary hypertension.

Reported here is a case of a patient with pulmonary arterial hypertension related to HIV (PAHRH) in which lipodystrophy necessitated interruption of highly active antiretroviral therapy (HAART) and long-term survival was the outcome. Although previous studies have suggested antiretroviral therapy may benefit patients with this rare complication of HIV infection, no worsening of PAHRH was observed when HAART was interrupted. Clinical and echocardiographic parameters remained stable during 7 months of follow up. In cases in which HAART is associated with relevant toxicity, interruption of HAART in patients with PAHRH can be considered, but should be used only if no alternatives are available. Close follow-up is warranted.

Adult↗
PubMed1999

[Socio-demographic and life-style factors in a Swiss study of HIV non-progression].

OBJECTIVES: The study investigates associations between socio-demographic or lifestyle factors and the progression of HIV. METHODS: We recruited a Swiss cohort (n = 56) of long-term survivors and conducted a cross-sectional study of laboratory data as well as factors concerning socio-demography, life-style, and psychology. On the basis of laboratory results, the cohort was divided into 2 subgroups, non-progressors (n = 31) and slow progressors (n = 25), which were subsequently compared. RESULTS: The comparison of socio-demographic factors showed that non-progressors were younger and had a higher income than slow progressors. Our data do not show an association between lifestyle and disease progression. DISCUSSION: Younger age as a cofactor of non-progression confirms various other studies. The association between income and disease progression, also found in another cohort, cannot be explained by unequal access to therapies since, in accordance with the inclusion criteria, no one in our cohort had received antiretroviral therapies. Further research in this field seems important to determine possible links between socio-economic status and disease progression. The lack of association between disease progression and lifestyle factors such as drug use, physical activity or nutrition is in contrast to a common view of HIV in our study population, but is confirmed by a majority of the research in this field.

Adult↗
PubMed1999

[Hepatitis C. Diagnostic and prognostic aspects from the insurance medicine viewpoint].

Hepatitis C is a chronic infection with potentially serious long-term effects. An acute clinical presentation is the exception, often the disease is only diagnosed through routine screening (e.g. as a blood donor) or work-up for elevated liver enzymes. The silent course of this disease also makes it difficult to interpret epidemiological studies. Potential biases need to be considered which may lead to underestimation or overestimation of prevalence and incidence data. Special attention is needed in evaluating long-term effects as the studies usually deal with small numbers of HCV positives and their selection may not have been randomised. An assessment of the prognosis is difficult, especially in the absence of a series of liver enzyme measurements and if the viral load is unknown. The wide availability of diagnostic tests harbours a potential for anti-selection. Caution is therefore required when designing underwriting guidelines; only well documented cases should be accepted. A response to therapy (e.g. with interferon), alone, does not prove a good prognosis, rather, the course over a 2-year follow-up may give relevant prognostic information.

Cause of Death↗
PubMed1998

Association of syncytium-inducing phenotype of HIV-1 with CD4 cell count, viral load and sociodemographic characteristics.

OBJECTIVES: To study whether syncytium-inducing (SI)/non-SI (NSI) phenotype of HIV-1 is associated with CD4+ lymphocyte count, plasma HIV RNA level, clinical stage and sociodemographic characteristics in antiretroviral-naive HIV-1-infected patients. DESIGN: Cross-sectional analysis of single centre cohort study data. METHODS: SI/NSI phenotype was determined using a cocultivation assay using patients' peripheral blood mononuclear cells and MT2 cells. Standard procedures were used for CD4+ cell counts and viral load measurements in plasma. Univariate and multivariate analyses of association of CD4+ cell counts, viral load, clinical stage, age, sex and mode of HIV transmission were performed. RESULTS: In univariate analysis, SI phenotype was significantly associated with lower CD4+ cell counts, higher HIV RNA plasma levels, symptomatic HIV disease, male sex and age 32-36 years (middle tercile). In multivariate analysis, only lower CD4+ cell counts were associated with SI phenotype (odds ratio per increase of 100 x 10(6)/l, 0.54; 95% confidence interval, 0.38-0.78). CONCLUSIONS: HIV-1 SI phenotype was associated with lower CD4+ cell counts but not with higher plasma viral load, clinical stage or sociodemographic variables.

Adolescent↗
PubMed1998

Single tube competitive PCR for quantitation of CMV DNA in the blood of HIV+ and solid organ transplant patients.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in transplant and HIV-infected patients. However, CMV can also cause asymptomatic infection. An elevated blood viral load as assessed by various methods appears to be a predictor for symptomatic infections, and can be used to identify patients at the highest risk of developing CMV disease. We developed a single tube competitive quantitative PCR assay for CMV DNA, using as a competitor a plasmid carrying the target sequence for amplification with an internal deletion. The analysis of data from repeated extractions and amplifications of samples showed that the coefficient of variation of the assay was typically less than 20%. Clinical samples from 14 HIV-infected and 13 solid organ transplant patients were analyzed. Widely varying CMV DNA levels were found in leukocytes, with a positive correlation with the measure of infectivity in the leukocytes by quantitative culture on fibroblasts. The highest CMV DNA content in leukocytes was found in two patients with presumptive CMV disease. In HIV patients, the amount of DNA in leukocytes was much larger than in solid organ transplant recipients, when standardized for infectivity. Although based on a very limited number of patients, this observation probably points to a difference in the biology of CMV infection in these two categories of susceptible individuals. CMV DNA was also found in the plasma of some of the patients with a high CMV DNA leukocyte load. The present test should be useful for identifying patients at high risk of developing CMV disease, for monitoring therapeutic efficacy of antiviral regimens and to improve the understanding the pathogenesis of CMV infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

[HIV infection: future perspective for a so-called fatal disease?].

During the last 18 months, our knowledge and possibilities in the field of HIV infections have progressed in four principal domains: (1) better understanding of the dynamics of HIV infections and in particular of the importance of viral replication during the phase of latency, (2) possibility of measuring the viral charge and its use for diagnosis and to follow treatment, (3) access to very effective new anti-retroviral substances which permit hope of long-term stabilization of the infection, (4) clinical demonstration that combined treatments are superior to monotherapy. While, at the beginning of 1996, only three medications were commercialized, there were eight at the end of that year. This paper describes the implications for daily practice of recent scientific discoveries in the field of HIV infection. The importance of compliance is discussed, as well as that of clinical research.

AIDS-Related Opportunistic Infections↗
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

Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland.

The objective of this study was to estimate the annual direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Days of hospital stay in 1992 were quantified using the casuistic of the medical statistics department of VESKA (Vereinigung Schweizerischer Krankenhäuser, the Swiss Hospital Association), which covers 43% of all hospital beds of that country. Number and incidence of total hospitalizations due to fractures were calculated by extrapolating to 100% the 43% VESKA-selected sample. To estimate number and incidence of hospitalizations due to osteoporotic fractures, internationally accepted age-specific osteoporosis attribution rates were applied. According to the latter the probability of a fracture being caused by osteoporosis increases with age. Mean length of stay for all fractures was calculated (= total hospital days divided by number of cases). By multiplying these mean lengths of stay by the number of osteoporosis-related fracture cases, the number of bed-days due to osteoporotic fractures was calculated. To compare the direct medical costs of hospitalization due to osteoporosis with those due to other frequent diseases, days of hospital stay caused by chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction and breast cancer were estimated using the same methodology. A total estimate of 63,170 (f: 33,596, m: 29,574) hospitalizations due to fractures (and other osteoporosis-related diagnoses) was calculated, thus leading to overall annual incidence rates of hospitalizations for fractures of 950/100,000 women and 877/100,000 men. In women, 548,615 hospital days were found to be caused by osteoporosis, 353,654 days by COPD, 352,062 days by stroke, 200,669 days by breast carcinoma and 131,331 days by myocardial infarction. In men, COPD caused more hospitalization days (537,164) than myocardial infarction (196,793), stroke (180,524) or osteoporosis (152,857). Taking a mean price for a hospital day in Switzerland of 845 Swiss francs, the annual costs of acute hospitalizations due to osteoporosis and its complications were approximately 600 million Swiss francs (f: 464, m: 130 million Swiss francs) in 1992. We conclude that there is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland.

Adolescent↗
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

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study.

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[HIV infection and splenectomy: 3 cases and literature review].

3 splenectomized patients infected by the human immunodeficiency virus (HIV) are described. They all presented with more than 500 CD4/mm3 but, surprisingly, with a CD4 percentage below 15, positive p24 antigenemia and a CD4/CD8 ratio below 0.24. 2 patients had repeated episodes of oropharyngeal candidiasis while their CD4 counts exceeded 800/mm3. These episodes suggested the presence of a certain degree of immuno-suppression and prompted us to introduce anti-HIV therapy. 2 patients also presented with a pulmonary infection, due to Klebsiella pneumoniae and Haemophilus influenzae respectively. The third patient had septicemia due to Streptococcus pneumoniae type 22, despite vaccination and a CD4 count above 700/mm3. In splenectomized HIV-infected patients the number of CD4 lymphocytes should be interpreted with caution, as this number increases after splenectomy. The CD4 percentage and CD4/CD8 ratio correlated better with the clinical stage of HIV infection and gave more valuable indications as to the degree of immunosuppression. A possible correlation between viremia and the number of CD4 lymphocytes in this subset of patients remains to be established. In HIV-infected patients, infections due to S. pneumoniae, H. influenzae, S. aureus and enteric gram-negative bacteria are frequent. After splenectomy, susceptibility to encapsulated bacteria increases even in HIV-negative patients. Early vaccination against the main strains of S. pneumoniae is essential, as vaccinal response is uncertain in patients with less than 400 CD4/mm3.

AIDS-Related Opportunistic Infections↗
PubMed1996

Inhibition of syncytia-inducing (SI) virus by autologous serum from HIV-1-infected individuals.

BACKGROUND: Progression from HIV infection to AIDS is often accompanied or even predicted by a switch of the virus to a more pathogenic or syncytia-inducing (SI) phenotype concomitant with the development of HIV variants escaping neutralizing antibodies. OBJECTIVE: Here we studied the capacity of sera to neutralize autologous SI-HIV or the laboratory strain III(B) and compared these data to the viral load in HIV-1-infected patients. METHODS: The SI phenotype of HIV was detected by co-cultivation of peripheral blood mononuclear cells (PBMCs) with MT2 cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1 : 15 and 1 : 75 were added to MT2 co-cultures with autologous PBMCs as well as with HIV-1/IIIB-infected H9 cells to study the inhibitory capacity. The p24 antigenemia was detected by enzyme-linked immunosorbent assay (ELISA) and the circulating HIV RNA was determined using the polymerase chain reaction (PCR). RESULTS: The SI virus was detected in PBMCs from 31/65 patients with < or = 200 CD4+ cells, 8/28 patients with 201-499 CD4+ cells, and 1/19 patients with > or = 500 CD4+ cells. Sera from 16/40 patients inhibited the autologous SI-HIV. In sera from patients with < or = 200 CD4+ cells, p24 antigen could be detected in 17/34 (50%) patients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%) patients carrying SI-HIV without serum inhibition. In contrast, all 12 sera with inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A similar tendency was seen in patients with higher CD4+ T-cell counts. The mean load of circulating HIV RNA did not differ among groups of patients. Independently of their neutralizing activity to the autologous SI virus, the majority of sera were able to neutralize the laboratory HIV-1/III(B). CONCLUSIONS: While most of the patients' sera neutralized the laboratory HIV-1/III(B) strain, only some sera were able to inhibit the autologous SI-HIV. In these cases, the detectable SI-HIV may still be controlled by the immune system in vivo, which is consistent with a low p24 antigenemia.

Journal Article↗
PubMed1996

Decreased release of glutathione into the systemic circulation of patients with HIV infection.

Low glutathione (GSH) in patients with HIV infection could contribute to their immune deficiency since GSH plays an important role in the function of lymphocytes and sulphydryls decrease the expression of HIV in vitro. In order to gain more insight into the mechanisms responsible for the deranged sulphydryl homeostasis in HIV infection, the release of GSH into the circulation, an estimate of the systemic production of GSH, was determined using a pharmacokinetic approach. The basal plasma concentrations of free GSH (3.3 +/- 1.3 vs. 5.3 +/- 1.9 mumol L(-1)) and cysteine (7.7 +/- 2.6 vs. 13.4 +/- 4.9 mumol L(-1)) were significantly lower in eight HIV-infected patients than in eight controls. Upon infusion of GSH at a constant rate of 1 mumol min-1 kg-1, GSH in plasma reached a new plateau. The increment in plasma GSH was significantly larger in the HIV-infected patients than in the controls. The input of GSH into the circulation (12.9 +/- 5.7 vs. 30.1 +/- 11.7 mumol min-1; P < 0.01) and the clearance of GSH (25 +/- 7 vs. 35 +/- 7 mL min-1 kg-1) were significantly lower in patients with HIV-infection. During infusion of GSH the concentration of cysteine in peripheral blood mononuclear cells of the HIV-infected patients increased significantly. Nevertheless, intracellular GSH did not increase. Thus, the consumption of GSH is not increased in HIV infection. Rather, the present data suggest that GSH in patients with HIV infection is low because of a decreased systemic synthesis of GSH.

Adult↗
PubMed1996

Reasons for failure of prevention of Toxoplasma encephalitis. Swiss HIV Cohort Study.

OBJECTIVE: To study whether absence of prophylaxis is a risk factor for cerebral toxoplasmosis, and to determine the reasons for absence of prophylaxis among AIDS patients diagnosed with Toxoplasma encephalitis (TE). DESIGN: Retrospective chart review and matched case-control study. PATIENTS: Patients (104 first episodes and 26 relapses of TE) were registered in the Swiss HIV Cohort Study from three centres from July 1992 to December 1994; 91 matched controls were included for 52 patients with a first episode, and 17 matched controls for 17 patients with relapse of TE. RESULTS: Prophylaxis was prescribed to 17 patients (16%) with a first episode and 19 patients (73%) with a relapse of TE. Reasons for the absence of prophylaxis included patient refusal (25%), non-proposal by physicians (17%), and drug intolerance (17%). Reduced absorption due to non-compliance, diarrhoea or vomiting was identified among 12 patients with a first episode and 14 patients with a relapse of TE. Absence of prescription of prophylaxis was associated with a 10-fold increased risk of a first episode of TE (odds ratio, 9.8; 95% confidence interval, 2.7-35.4) in the matched case-control study. CONCLUSIONS: TE continues to occur among patients not receiving prophylaxis. At least one-half of the cases may be prevented with better motivation of physicians and increased compliance of patients.

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

Infection control in Switzerland.

Infection control in hospitals is not mandatory in Switzerland as in the United States. There are more than 300 acute-care hospitals in Switzerland. Hospitals are reimbursed by patient-days rather than diagnosis-related group. However, all five Swiss university hospitals have developed an infection control program. The major criteria for setting up and running these programs are reviewed; data are based on a questionnaire and personal interviewing of each institution. Most of the major criteria exist in all five institutions. Resources allocated to infection control differ markedly. The number of infection control nurses per 250 beds varies between 0.2 and 0.75 for the five hospitals; the activity of those in charge of infection control differs between hospitals. A comparison is made between the Swiss and U.S. programs with regard to some aspects of healthcare and infection control.

Cross Infection↗
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↗