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Biomedical subjects

R Lüthy

Publications and source records attributed to R Lüthy.

At least 163 records · Page 9Linked to original sources

[Heterosexual transmission of the acquired immunodeficiency syndrome (AIDS)].

A man who, only in 1979 and on a few occasions, had homosexual contacts, transmitted AIDS virus HTLV-III in 1980 and 1981 to two previously healthy women who did not belong to any AIDS risk group. One of them now has an early form of AIDS, while the other died of AIDS in its full form and her child, born in 1983, has fairly far progressed early symptoms of AIDS. Serum antibodies against HTLV-III were demonstrated in all four subjects.

Acquired Immunodeficiency Syndrome↗

[Prevalence of antibodies against HTLV-III in various regions in Switzerland].

Acquired immune deficiency syndrome (AIDS) has been etiologically linked with the human T-cell lymphotropic virus HTLV-III. In a study on the prevalence of antibodies to this virus in Switzerland, sera from 941 individuals were collected in 5 major urban areas (Basel, Berne, Geneva, Lausanne and Zurich) in 1983 and 1984. All sera were tested by ELISA and the majority also by Western blot. We found an antibody prevalence of 100% among 22 cases of AIDS, of 94% among 48 cases of AIDS-related complex (ARC), and of 57% among 14 homosexual contacts of AIDS patients. Among 55 sera collected from i.v. drug addicts in 1984, 53% were positive, whereas the rate had been 36% among 103 sera collected in 1983. The rate was 19% among 227 sera collected from asymptomatic active homosexuals in 1984, against 10% among 40 sera collected in 1983. 8% positives were found among 98 patients with various types of viral hepatitis. In addition, 4% of 84 sera of individuals from Equatorial Africa were positive. No positives were found among 15 sera of individuals from other African regions, among 32 sera of persons from various regions of Asia, and among 203 Swiss blood donors. These results demonstrate the high and increasing rate of HTLV-III infection among groups at risk for AIDS, and suggest that HTLV-III-related diseases will be a serious problem in the years ahead.

Acquired Immunodeficiency Syndrome↗

[Acquired immunodeficiency syndrome (AIDS). An update after 4 years].

At the end of December 1984, 8246 AIDS cases had been reported in the United States, and 762 cases in Europe. The main risk groups are homosexual and bisexual men (73%), heterosexual i.v. drug addicts (17%) and Haitians (4%). AIDS is diagnosed in patients meeting the clinical criteria of the CDC surveillance definition (opportunistic infections and/or Kaposi's sarcoma). The prevalence of HTLV-III antibodies in risk groups is high, its prognostic significance still controversial. Laboratory methods to determine the more relevant circulating viral proteins or the whole virus are now being developed. Limited studies to evaluate the possibility of reconstituting the immune system of AIDS patients with interleukin-2 and gamma-interferon have proved unsuccessful. successful. Several new drugs with possible antiviral properties are now being evaluated in first clinical trials.

Acquired Immunodeficiency Syndrome↗

Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS.

We tested serum samples from Swiss subjects by three different assays based on enzyme-linked immunosorbent assay (ELISA) and Western blot techniques for antibodies to proteins associated with the recently discovered human T-cell leukemia/lymphoma virus HTLV-III, the putative etiologic agent for the acquired immunodeficiency syndrome (AIDS). Of 10 patients with AIDS and 10 with pre-AIDS, all were antibody-positive. Furthermore, 37 of 103 intravenous-drug addicts (36 per cent), 4 of 40 healthy homosexual men (10 per cent), 7 of 83 patients with various types of hepatitis (8.4 per cent), but none of 83 healthy blood donors or 10 other controls were antibody-positive. Antibodies to the major viral protein p24 were found consistently and at high titers in the seropositive members of the groups at risk and in those with pre-AIDS but were dramatically reduced in patients with AIDS. In contrast, antibodies to another virus-associated protein, p41, were present in all cases of AIDS and pre-AIDS but were absent in nearly 10 per cent of seropositive persons at risk. Whereas p41 and p24 thus appear to be the targets of choice for future screening tests, the ELISA test that is currently available is a useful screening tool.

Acquired Immunodeficiency Syndrome↗

Progressive diffuse leukoencephalopathy in patients with acquired immune deficiency syndrome (AIDS).

Two adult patients with acquired immune deficiency syndrome (AIDS) presented with psycho-organic symptoms produced by an extensive cerebral and cerebellar leukoencephalopathy. Diffuse loss of myelin and axons with reactive astrocytosis and distinctive multinucleated giant cells were prominent in the deep white matter, but less so in the subcortical white matter and in compact myelinated pathways. Bilateral involvement of the centrum semiovale produced distal Wallerian degeneration of the descending pyramidal tracts, which in one patient correlated with progressive paraparesis and bladder dysfunction. Although there were morphological indications of cytomegalovirus infection and immunohistochemical evidence of papovavirus antigens, the neuropathology did not resemble that usually associated with infection by these opportunistic agents. The possibility is entertained that the progressive diffuse leukoencephalopathy (PDL) in these patients was directly related to infection with human T-cell lymphotropic virus (HTLV-III/LAV), the etiologic agent of AIDS.

Acquired Immunodeficiency Syndrome↗

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↗

Aminoglycoside monitoring: timing of peak levels is critical.

Recommendations for optimal therapeutic peak concentrations of aminoglycosides are often not differentiated with respect to duration of infusion and timing of peak sample thereafter. To document the relevance of the timing, 139 dose intervals were analyzed in 58 patients during administration of gentamicin, amikacin, and netilmicin. Serum concentrations measured immediately after 30-min infusions were compared with concentrations obtained 90 min later (2 h values). The ratio of 30 min/2 h concentrations showed considerable variability. This ratio was less than 1.5 in 15% of the dose intervals analyzed and greater than 3 in 8% of the intervals. The poor correlation between concentrations measured at 30 min and at 2 h was documented by the coefficients of variation of 0.82, 0.30, and 0.67 for gentamicin, amikacin, and netilmicin, respectively. This variability was not explained by interindividual differences, renal function, or drug half-life. However, the initial decrease in concentrations was significantly lower in patients with impaired renal function (p less than 0.001). These data suggest that timing is critical for the sampling of serum to determine peak levels in patients and the definition of optimal therapeutic concentrations.

Aminoglycosides↗

[Cardiovascular risk factors: an intervention program for general practice].

A new multiple risk factor intervention program, combining a comprehensive, stepwise and health education-based approach, was tested in an outpatient setting. In the first 47 patients (aged 17-55, referred by their physicians) total cardiovascular risk (estimated by Framingham index) was reduced within the first 12 months by an average of 32.5%. This improvement derived from significant reductions in all major risk factors. These findings demonstrate the feasibility and potential, yet unexploited, benefit of a more comprehensive risk factor, approach in general medical practice.

Adolescent↗

[Acquired immune deficiency syndrome in the region of Zurich. Report on 12 cases].

Observations of 12 patients with AIDS at this institution from March 1981 to April 1984 are reported. Ten patients were homosexuals and two were bisexual. The majority had travelled abroad (USA, Haiti) and reported multiple anonymous sexual contracts. Eleven patients reported symptoms and signs, of 2-12 months' duration, frequently seen in pre-AIDS: fatigue (10), weight loss (10), diarrhea (7), night sweats (5), fever (4), and generalized lymphadenopathy (1). Laboratory studies showed anemia (10), lymphopenia (9), leukopenia (7), decreased T-helper/T-suppressor ratio (10) and cutaneous anergy to multiple skin-test antigens (9). P. carinii pneumonia was diagnosed in three patients, P. carinii pneumonia and Kaposi's sarcoma in one patient and Kaposi's sarcoma in six patients. Another patient had a chronic mucocutaneous infection with herpes simplex and another an intestinal cryptosporidiosis and Kaposi's sarcoma. Alpha-A-interferon was used to treat patients with Kaposi's sarcoma and three patients with limited disease showed a favorable response. Six patients with advanced disease died.

Acquired Immunodeficiency Syndrome↗

[Prevention of endocarditis using amoxycillin, clindamycin or erythromycin. Pharmacokinetic observations].

Current recommendations for antibiotic prophylaxis of bacterial endocarditis include oral amoxycillin, and erythromycin or clindamycin for the penicillin-allergic patient. The authors report the serum concentrations and side effects which may be expected after the recommended oral doses of these compounds. Single doses of 3 g amoxycillin and 600 mg clindamycin, and two doses of erythromycin (1.5 g and 0.5 g 6 h apart) were administered in a random sequence to each of 12 volunteers. After administration, peak serum concentrations of amoxycillin and clindamycin were 27 mg/l and 5.5 mg/l respectively. Amoxycillin was eliminated more rapidly than clindamycin. Serum concentrations of erythromycin were below the sensitivity limit of the assay (0.03 mg/l) in 3 volunteers at 1 h and in 2 at 2 h. The mean peak serum concentrations was 3.1 mg/l. Peak levels were associated with gastrointestinal side effects such as nausea, abdominal cramps and vomiting. The implications of these findings are discussed with respect to use of these antibiotics for the prophylaxis of bacterial endocarditis.

Amoxicillin↗