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Biomedical subjects

M Egger

Publications and source records attributed to M Egger.

At least 19 recordsLinked to original sources
PubMed1999

Erythropoietin modulates intracellular calcium in a human neuroblastoma cell line.

1. Recent investigations have shown that the glycoprotein erythropoietin (Epo) and its specific receptor (EpoR) are present in the mammalian brain including human, monkey and mouse. These findings suggest a local action of Epo in the nervous system. The aim of this study was to elucidate a possible functional interaction of Epo with neuronal cells. 2. To examine the influence of externally applied Epo on Ca2+ homeostasis the human neuroblastoma cell line SK-N-MC was chosen as a suitable in vitro model for undifferentiated neuronal cells. 3. Expression of the EpoR in SK-N-MC cells was detected by reverse transcription-PCR, Western blot and immunofluorescence analysis. 4. Patch-clamp studies of SK-N-MC cells confirmed the expression of T-type Ca2+ channels, whose peak macroscopic current was increased by the addition of recombinant human Epo (rhEpo) to the bathing medium. 5. Confocal laser scanning microscopy analysis of SK-N-MC cells confirmed a transient increase in intracellular free [Ca2+] in response to externally applied rhEpo. 6. The transient response to Epo was dependent on external Ca2+ and remained even after depletion of internal Ca2+ stores by caffeine or thapsigargin. However, after depletion the response to Epo was absent when cells were superfused with the T-type Ca2+ channel blocker flunarizine. 7. This study demonstrates that Epo can interact with neuronal cells by affecting Ca2+ homeostasis through an increase in Ca2+ influx via plasma membrane T-type voltage-dependent Ca2+ channels.

Blotting, Western↗
PubMed1999

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003). CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.

Anti-Bacterial Agents↗
PubMed1999

Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) in suppression of HIV-1 is well documented. We investigated virological and clinical outcomes of HAART in routine practice. METHODS: We analysed prospective data from the Swiss HIV Cohort Study on suppression of viral load and progression to AIDS or death in 2674 outpatients (median age 36 years, 27.3% women) who started HAART in 1995-98. Viral rebound was defined as two consecutive HIV-1-RNA measurements of more than 400 copies/mL. We analysed separately outcomes in patients with a history of antiretroviral treatment and in treatment-naïve patients. FINDINGS: An estimated 90.7% of treatment-naïve patients reached undetectable viral load (<400 copies/mL) by 12 months. Among pretreated patients, estimates ranged from 70.3% treated with one new drug to 78.7% on three new drugs. 2 years after reaching undetectable concentrations, an estimated 20.1% of treatment-naïve patients and 35.7-40.1% of pretreated patients had viral rebound. At 30 months, an estimated 6.6% (95% CI 4.6-8.6) of patients who had maintained undetectable concentrations, 9.0% (5.5-12.5) who had viral rebound, and 20.1% (15.3-24.9) who had never reached undetectable concentrations developed AIDS or died. Compared with patients who maintained undetectable viral load, the adjusted relative hazard of AIDS or death was 1.00 (0.66-1.55) for patients with viral rebound, and 2.40 (1.72-3.33) for patients who failed to reach undetectable concentrations. INTERPRETATION: The rate of virological failure of HAART was high among these patients, but the probability of clinical progression was low even in patients with viral rebound.

Adult↗
PubMed1998

[Under the meta-scope: possibilities and limits of meta-analyses].

Critical review and statistical synthesis of the best evidence that is available on the benefits and risks of medical interventions is an important component of evidence-based medicine. There is, however, controversy regarding the merits and perils of this approach. In this article the potential and limitations of meta-analysis are illustrated and the problems of applying meta-analytical results to the individual patient are discussed. Whereas the classical narrative review article often reflects the personal opinion of the author, systematic reviews are characterized by clearly defined objectives and reproducible methods. If appropriate and feasible, individual studies are combined in a meta-analysis which will lead to enhanced precision of effect estimates. The potential of meta-analysis is illustrated by considering a patient who suffered a myocardial infarction in 1981. After consulting a misleading narrative review, this patient was discharged without beta-blockade for secondary prevention. Meta-analyses are, however, also liable to bias. For example, a meta-analysis of trials of magnesium infusions in acute myocardial infarction showed a substantial reduction in mortality. The beneficial effect of magnesium was not confirmed in the large ISIS-4 trial published in 1995. The occurrence of misleading meta-analyses is not surprising considering the selective publication of "positive" findings and the often inadequate quality of component studies. Misleading meta-analyses may also result from the inappropriate combination of heterogeneous studies. Every patient is unique regarding the exact localization and severity of the lesion, preexisting abilities, co-morbidity, social environment, personality and emotional response. The appropriate application of meta-analytic findings to the individual patient is difficult. It requires consideration of both quantitative and qualitative approaches to decision-making. Emphatic integration of these approaches characterizes the experienced, scientifically and socially competent physician.

Clinical Competence↗
PubMed1998

Reporting on quality of life in randomised controlled trials: bibliographic study.

OBJECTIVES: To examine the frequency and quality of reporting on quality of life in randomised controlled trials. DESIGN: Search of the Cochrane Controlled Trials Register 1980 to 1997 to identify trials from all disciplines, from oncology, and from cardiovascular medicine that reported on quality of life. Assessment of abstracts from articles published from 1993 to 1996. Assessment of a sample of full reports with a standardised instrument. MAIN OUTCOME MEASURES: Prevalence of reporting on quality of life. Conditions and interventions studied in trials reporting on quality of life. Quality of reporting on quality of life. RESULTS: During 1980-97 reporting on quality of life increased from 0.63% to 4.2% for trials from all disciplines, from 1.5% to 8.2% for cancer trials, and from 0.34% to 3.6% for cardiovascular trials. Of 364 abstracts, 65% reported on drug interventions. Of a sample of 67 full reports, authors of 48 (72%) used 62 established quality of life instruments. In 15 reports (22%) authors developed their own measures, and in 2 (3%) methods were unclear. Response rates were given in 38 (57%), and complete reporting on all items and scales occurred in 31 (46%). CONCLUSIONS: Less than 5% of all randomised controlled trials reported on quality of life, and this proportion was below 10% even for cancer trials. A plethora of instruments was used in different studies, and the reporting of methods and results was often inadequate. Standards for the measurement and reporting of quality of life in clinical trials research need to be developed.

Data Collection↗
PubMed1998

Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study.

BACKGROUND: AIDS reporting in Switzerland is mandatory by law. For the first time since the beginning of the epidemic, health authorities observed a decline in AIDS surveillance reports, from 545 new cases in 1995 to 459 in 1996, a decrease of 86 cases. OBJECTIVE: To examine the extent to which this decline in AIDS surveillance reports is attributable to the introduction of antiretroviral combination therapy. PATIENTS AND SETTING: Swiss HIV Cohort Study, a multicentre cohort of adult HIV-infected patients with national coverage. Participants at risk of developing a first AIDS-defining event, defined as persons with a CD4 cell count below 200 x 10(6)/l or in clinical stage B, were studied. METHODS: A parametric statistical survival model was used to estimate the number of AIDS cases expected in the absence of combination therapies. Taking reporting delays into account, the effect of the introduction of combination therapies in the cohort on national AIDS reports was estimated from the difference between the number of expected and observed cases. RESULTS: A total of 4915 participants contributed 10755 person-years and 2366 initial AIDS events. Between 1990 and 1994, about 35% received antiretroviral therapy, predominantly monotherapy. In 1995 and 1996, the prevalence of antiretroviral therapy increased steadily due to the introduction of dual and triple combinations. The mid-year prevalence of use of combination therapies was 6% in 1994, 13% in 1995, and 48% in 1996. The difference between expected and observed cases per half-year increased from 12 in the first 6 months of 1994 to 69 in the second half of 1996. Taking reporting delays into account, we estimated that 43 (95% confidence interval, 17-69) of the deficit of 86 reports could be attributed to combination therapies. CONCLUSION: The introduction of antiretroviral combination therapies in a single cohort study explained 50% of the decline in national AIDS surveillance reports. Monitoring the use and effectiveness of antiretroviral therapy must become an important component of AIDS surveillance systems.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis.

OBJECTIVES: To analyse trends in rates of genital chlamydial infection and ectopic pregnancy between 1985 and 1995 in a county in Sweden. SETTING: Uppsala county where screening for chlamydial infection, treatment, and contact tracing has been widespread and where ectopic pregnancies are recorded. METHODS: Rates of chlamydial infections and ectopic pregnancy between 1985 and 1995 were calculated for women aged 20-39 years. Poisson and linear regression were used to examine the association between the risk of ectopic pregnancy and the current rates of chlamydial infection and rates of chlamydial infection from up to 5 years earlier. MAIN OUTCOME MEASURES: Rates of chlamydial infection per 100 examinations, rates of ectopic pregnancy per 1000 pregnancies, rate ratios and 95% confidence intervals for an increase in chlamydial infections of 5 new cases per 100 examinations. RESULTS: 103 870 cervical samples from women aged 15-39 years were analysed; 5648 (5.4%) were positive for chlamydia. 51 630 pregnancies were analysed; 930 (1.8%) were ectopic. Both rates declined over time. For women aged 20-24 years there was a strong correlation between the rate of ectopic pregnancy and the rate of chlamydial infection in the same year (r=0.93, P<0. 001); among older women correlations were stronger with rates of chlamydial infection occurring 1 or 2 years earlier. In Poisson regression ectopic pregnancy was most strongly associated with the current rate of chlamydial infection among women aged 20-24 (rate ratio 1.85, 95% confidence interval 1.44 to 2.38), with the rate of infection 1 year earlier among 25-29 year olds (rate ratio 1.72, 1. 33 to 2.22) and 30-34 year olds (rate ratio 2.27, 1.53 to 3.37); and with the rate 2 years earlier among 35 to 39 year olds (rate ratio 2. 58, 1.45 to 4.60). CONCLUSIONS: Declining rates of genital chlamydial infections have probably led to a fall in the rate of ectopic pregnancies. The timing of the decline in the rate of ectopic pregnancies varies with age. Among young women falling rates of chlamydial infection have been accompanied by an immediate reduction in the rate of ectopic pregnancy.

Adolescent↗
PubMed1998

Does pregnancy influence the course of HIV infection? Evidence from two large Swiss cohort studies.

The question whether the natural history of HIV infection in women is affected by pregnancy has not so far been convincingly answered. We used prospective cohort data to compare pregnant and nonpregnant HIV-infected women during follow-up within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had been made before conception had taken place. Additional inclusion criteria were a pregnancy completed to delivery during follow-up and an observation period of at least 6 months after delivery. Thirty-two women who fulfilled these criteria were compared with 416 controls, matched for age and CD4 cell count at entry, who had not been pregnant during follow-up. Mean follow-up time was 4.8 years for pregnant women and 3.6 years for controls. The rate of any AIDS-defining event was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95% confidence interval [CI], 0.80-4.64) but this did not reach statistical significance (p = .15). A statistically significant difference (p = .008) emerged only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95% CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95% CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell counts before conception into account, acceleration of disease progression is inconsistent among HIV-infected women who become pregnant during follow-up.

AIDS-Related Opportunistic Infections↗