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F D Goebel

Publications and source records attributed to F D Goebel.

232 records · Page 13Linked to original sources
PubMedDate not supplied

Pharmacokinetics of orally administered zidovudine in HIV-infected children and adults.

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.

Administration, Oral↗
PubMedDate not supplied

Hyperlipidemia under treatment with proteinase inhibitors.

To define the extent and time course of HIV-proteinase inhibitor (PI) effects on serum lipid levels 148 patients on triple combination therapy including PIs and 91 patients on therapy with two nucleosides as a control group were evaluated. In the PI group there was a significant increase in total cholesterol after 3, 6 and 12 months compared to the baseline level (198, 204 and 203 vs. 176 mg/dl). The increase in triglycerides was 25.5% from the baseline at month 3. Indinavir had a significantly higher impact on cholesterol levels than saquinavir. No changes in lipids were seen in the control group. It was concluded that hyperlipidemia is associated with PI use, becomes evident within 3 months of treatment and seems to be substance specific.

Adult↗
PubMedDate not supplied

Th1/Th2 shift in HIV lymph nodes: no contribution of CD6o cells.

BACKGROUND: An expansion of CD8+60+ cells with Th2 type helper function has been observed in HIV-infected individuals. A Th1/Th2 shift in late HIV infection might be related to the functional activity of this subset. Our objective was to test the ability of lymph node (LN) lymphocytes to produce cytokines of the Th1 and Th2 type. PATIENTS AND METHODS: LN cells were stimulated with PMA in the presence of ionomycin and brefeldin A. After surface staining for CD4, CD8 and CD60 and intracellular staining for interferon gamma (IFNgamma), interleukin 2 (IL-2) or IL-4 and IL-10, the percentage of cytokine producing lymphocytes (CPL) was determined by flow cytometry. LN of nine individuals in the early stage of HIV infection were compared to late stage patients. RESULTS: CD4+ subset: in early stages of HIV infection the percentage of Th1 CPL was 1.9 times higher than that of Th2 CPL. In late stages of infection the Th1 responding cells were not found more frequently than Th2 ceLLs. CD8+ subset: no Th1/Th2 shift was detected during early or late stages of HIV infection. CD60+ subset: a maximum of 32.1 +/- 7.8% of double positive cells of the CD8+60+ type produced Th2 type cytokines. A small percentage (< 8%) of CD60+ cells also produced Th1 cytokines. No shift in the cytokine production was seen in early or late stages of infection. CONCLUSION: At single cell level a shift in cytokine production in LN cells can only be detected in the CD4+ subset. Thus, the CD60+ subset does not seem to contribute to the putative Th1/Th2 shift attributed to the immunopathogenesis of HIV-induced destruction of the immune system.

Antigens, CD↗
PubMedDate not supplied

Liposomal doxorubicin in the treatment of AIDS-associated Kaposi's sarcoma: clinical, histological and cell biological evaluation.

AIDS-associated Kaposi's sarcoma (KS) in eight patients was treated with the systemic application of liposomal doxorubicin (20 mg/m2 per cycle). After six cycles of treatment a significant regression of KS was observed in all patients. Tumour volume was reduced from 556 +/- 635 mm3 before therapy to 42 +/- 134 mm3 after therapy as determined by ultrasonography of selected tumours. Histological examination revealed a reduction of tumour-like structures and the absence of KS spindle cells in involved areas after therapy. In vitro experiments with KS-derived cell cultures, which most likely represent the KS spindle cells, suggested that liposomal doxorubicin may cause regression of KS via two different mechanisms: (i) by highly specific inhibition of KS spindle cell proliferation and (ii) by induction of monocyte chemoattractant protein-1 expression in KS spindle cells, which may result in increased recruitment of phagocytic cells (monocytes/macrophages) into the lesions. A cooperative action of both mechanisms may explain the high efficacy of liposomal doxorubicin in the treatment of AIDS-KS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Cranial sclerosis with striated bone disease (osteopathia striata).

This report concerns another case of striped bone disease (Osteopathia striata) together with sclerosis of the base of the skull. The mode of inheritance of this rare genetic disorder is still unknown. The clinical characteristics of 20 cases reported in the international literature are summarized and compared with our own findings.

Adolescent↗
PubMedDate not supplied

Fluconazole-resistant oral candidosis in a repeatedly treated female AIDS patient.

A 29-year-old female suffering from full-blown AIDS received fluconazole 400 mg day-1 for a long period for treatment of oral candidosis, pseudomembranous type. She had previously received this drug repeatedly for the same reason, yet manifest disease persisted. She was therefore put on parenteral amphotericin B, which led to clinical, but not mycological, cure in the short term. IC30 testing revealed a minimum inhibitory concentration (MIC) > 128 micrograms ml-1 for fluconazole. The isolate, however, was susceptible in vitro to ketoconazole, itraconazole and amphotericin B. The same antimicrobial susceptibility pattern was found with a second isolate obtained later. Resistance to fluconazole might become a major problem in HIV-infected patients receiving this drug for long periods.

AIDS-Related Opportunistic Infections↗