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Biomedical subjects

B Ledergerber

Publications and source records attributed to B Ledergerber.

68 records · Page 4Linked to original sources

[The prognostic value of different patterns of change in the CD4 lymphocyte counts in 420 symptom-free HIV-1-infected persons].

The pattern of change over time of CD4-lymphocyte counts was investigated prospectively in 420 patients infected with HIV-1 (106 women, 314 men; mean age 34.9 [21-70] years) to assess its value in prognosticating progression to AIDS. Only those CD4-lymphocyte values were taken into account which had been measured in the asymptomatic stage of the HIV infection and before introduction of antiviral treatment. An average of 4.5 (range 3-10) measurements per person were available. Mean observation time was 2.4 years, the mean annual CD4-lymphocyte decrease was 48 cells/microliters. 121 patients (28.8%) had a fall in CD4-lymphocyte count which in the regression analysis significantly differed from zero. In this group there occurred 19 progressions to AIDS (15.7%), in contrast to only 20 (6.6%) in the 299 patients with a nonsignificant CD4 fall (P < 0.01). Multivariate analysis with the Cox regression indicated that the annual reduction in the CD4 count and the initial CD4 count were the only values of prognostic significance regarding progression to AIDS. There was no evidence that percentage and absolute CD4-lymphocyte counts had a different predictive value. When the initial CD4 count was high (> 900 cells/microliters), there was on average a steeper reduction in CD4-lymphocyte counts than when it was lower. This findings argues against a linear CD4 fall during the total period of observation. The annual CD4 fall, described with linear regression, is a prognostic criterion on its own for early recognition of those patients at a high risk of progression to AIDS while still in the asymptomatic stage of HIV infection.

Acquired Immunodeficiency Syndrome↗

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↗

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↗

[The natural history and laboratory parameters of HIV infection].

Since 1983 the morbidity and mortality rates as well as results of haematological, immunological and (later) HIV serological tests were recorded prospectively for 497 HIV-positive patients during 1837 clinic visits at least twice within at most six months for a median period of observation of 18 months (range 6-64 months). The rate of progression to a higher stage was calculated according to the method of Kaplan-Meier. The rate for asymptomatic patients was 16% after one and 33% after two years; for patients with persisting generalized lymphadenopathy it was 13% and 21%, respectively, for those with AIDS-related complex 28% and 47%, respectively, and for those with AIDS 33% and 82%, respectively. As for results of laboratory tests, patients with progressive disease had significantly lower titres of anti-HIV nuclear antibodies, as well as a higher incidence of HIV-p24 antigen. Haemoglobin levels, platelet and lymphocyte counts and number of CD-4-positive lymphocytes were significantly lower, Neopterin and beta 2-microglobulins higher (P less than 0.01).

AIDS-Related Complex↗

[HIV serological parameters in the prognosis and follow-up assessment of an HIV infection].

53 individuals negative for anti-HIV by screening test and 79 individuals positive for anti-HIV were prospectively surveyed for clinical progression and by quantitatively measuring anti-p24 (antibodies against an HIV core protein), anti-gp41 (antibodies against an HIV surface protein) and HIV-(p24) antigen. The patients were classified into four categories of HIV-markers: 1. Anti-p24 in high concentrations, HIV-Ag negative, 2. anti-p24 in high concentrations, HIV-Ag positive (most often transitory only), 3. anti-p24 absent/deficient, HIV-Ag negative and 4. anti-p24 absent/deficient and HIV-AG positive. Within a minimum of 18 months, 4 of the 53 (8%) initially anti-HIV negative individuals contracted HIV infection. 17 of the 79 (22%) initially anti-HIV positive individuals showed disease progression. 8 of the patients in category 4 already had AIDS when entering the study, and 3 of the 6 (5%) remaining patients of this category developed AIDS. Amongst the 19 patients in the third category 2 individuals (11%) developed AIDS and in a further 5 (26%) individuals the disease progressed but in no case to AIDS. None of the patients of the categories 1 and 2 developed AIDS but 2 of the 10 (20%) individuals in the second category and 3 of the 29 (10%) in the first category showed disease progression but not to AIDS. In conclusion, the quantitative measurement of anti-p24 and of HIV-Ag affords prognostic pointers for the clinical outcome of HIV infection.

AIDS-Related Complex↗

Prevalence of HIV antibodies among prostitutes in Zürich, Switzerland.

The prevalence of antibodies to the human immune deficiency virus was determined in 123 prostitutes. Of 18 intravenous drug abusers 14 were anti-HIV positive, all others, with one exception, were seronegative. Neither race, nor number of clients, nor sexual practices correlated with seropositivity.

Acquired Immunodeficiency Syndrome↗

Prevalence of HIV antibodies in groups at risk in Zürich, Switzerland.

The prevalence of HIV antibodies in various groups at risk was studied in 1,546 persons in Zürich. The prevalence was 17% (39/236) in homosexual men, 7% (13/180) in bisexual men, and 45% (14/31) and 42% (22/53) in female and male intravenous drug abusers, respectively. Heterosexual transmission appeared to be the route of infection in four seropositive persons (two women and two men) who had no homosexual contacts and were not drug abusers (4/1050).

Acquired Immunodeficiency Syndrome↗

[HTLV-III antibodies and risk factors for healthy homosexuals in Zurich].

Sera of 100 healthy homosexual men were tested for antibodies to AIDS virus HTLV-III. Significant differences were found between 45 seropositive and 55 seronegative men, such as a higher number of sexual partners per year, more contacts with AIDS patients, positive serological markers for syphilis, and reduced skin reaction after intradermal application of 7 recall antigens.

Adult↗

Computer-controlled in-vitro simulation of multiple dosing regimens.

The bactericidal effect of gentamicin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days. The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses. It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occur.

Computers↗

Effect of standard breakfast on drug absorption and multiple-dose pharmacokinetics of ciprofloxacin.

Ciprofloxacin was administered to 10 volunteers, who received seven oral doses of 250 mg each at 12-h intervals. Volunteers alternately fasted (F) or received a standard breakfast (B) before the morning dose. Pharmacokinetic parameters were derived from high-pressure liquid chromatography data from samples taken after the first and seventh doses and were analyzed in addition for differences caused by food intake. A significant (P less than 0.05) influence of the standard breakfast on the time to the peak was observed. Peak levels (+/- standard deviation) after the first and seventh doses averaged F (fasting): 1.35 +/- 0.17, B (breakfast): 1.02 +/- 0.28 micrograms/ml, and F: 1.41 +/- 0.32, B: 1.17 +/- 0.5 micrograms/ml, respectively. Mean trough concentrations after the first and seventh doses were F: 0.10 +/- 0.03, B: 0.14 +/- 0.03 micrograms/ml, and F: 0.16 +/- 0.05, B: 0.14 +/- 0.04 microgram/ml, respectively. As with the peak, trough concentrations were not affected significantly by food intake or by accumulation over the study period. Breakfast equally did not affect the terminal half-lives, which averaged F: 3.97 +/- 0.67, B: 4.35 +/- 0.88 h after the first dose and F: 4.64 +/- 0.91, B: 3.72 +/- 0.84 h after the seventh dose. Twelve-hour urinary recovery measured by high-pressure liquid chromatography averaged F: 31, B: 30% for the first dose and, in spite of a possible carry-over from the sixth dose, decreased to F: 25, B: 28% after the seventh dosing interval. When measured by bioassay, an increase of urinary recovery between the first dose (F: 38, B: 38%) and the seventh dose (F: 45, B: 45%) was observed. These differences suggest induction of drug metabolism with repeated doses. Ciprofloxacin was well tolerated by the volunteers.

Adult↗

Comparison of high-pressure liquid chromatography and bioassay for determination of ciprofloxacin in serum and urine.

Ciprofloxacin was given orally to 10 healthy volunteers for seven consecutive doses of 250 mg every 12 h. Serum and urine samples were collected at distinct times between 0 and 96 h and analyzed both by high-pressure liquid chromatography and by a microbiological assay. The detection limits were 0.006 and 0.03 microgram/ml, respectively. For each method, imprecision coefficients of variation were less than 6.1% at various concentrations in serum and urine. The means +/- standard deviations of the absolute values of the relative differences between the two methods were 9.3 +/- 6.8% (n = 225) for serum samples and 58.5 +/- 50.4% (n = 70) for urine samples. Comparison of the concentrations in serum measured with high-pressure liquid chromatography and bioassay by regression analysis yielded a slope which was not significantly different from 1.0 (99.9% confidence limits: 0.984 less than slope less than 1.035). In urine, however, the bioassay results were markedly higher than the high-pressure liquid chromatography values (1.327 less than slope less than 1.698), which indicates the presence of antimicrobially active metabolites. The cumulative 12-h urinary recovery after the first and seventh doses averaged 30.2 +/- 8.5 and 26.4 +/- 4.6%, respectively, by high-pressure liquid chromatography, whereas with bioassay 38.2 +/- 5.9 and 45.5 +/- 5.9% activity was recovered. Protein binding appeared to be neither concentration nor pH dependent and averaged 21.9 +/- 4.1%.

Adult↗