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S Wenzel

Publications and source records attributed to S Wenzel.

63 records · Page 4Linked to original sources

Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial.

OBJECTIVE: To establish the efficacy and acceptability of combined continuous low-dose oestrogen and low-dose progestogen therapy, to determine whether any of three commercially available progestogens had any advantages or disadvantages in these circumstances and whether use of the lowest clinically effective oestrogen dose affected other outcomes being measured. DESIGN: A 12-month, prospective, open label, single centre, randomised trial. PATIENTS AND METHODS: Seventy-five postmenopausal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medroxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding were changed to a continuous daily regimen of 0.3 mg CEE and a random allocation of one of three low-dose progestogens (medroxyprogesterone acetate 2.5 mg, levonorgestrel 30 micrograms or norethisterone 350 micrograms). Return to a dose of 0.625 mg CEE was permitted if required to control menopausal symptoms with separate analysis of this group when appropriate. OUTCOMES MEASURED: Menopausal symptom score, clinical bleeding pattern, endometrial biopsy results, forearm bone density and content, serum lipids and side effects. RESULTS: Fifteen women withdrew from the trial, five because of irregular bleeding. In the remainder, amenorrhoea was achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 months in all but one patient, in whom minimal proliferative activity was seen. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of menopausal symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects were experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups. CONCLUSIONS: These low-dose continuous oestrogen and progestogen regimens appear an appropriate option for the postmenopausal woman wishing to eliminate withdrawal bleeding and reduce both hormonal side effects and menopausal symptoms. The long term benefits of these regimens with regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time.

Bone Density↗

Suggested approaches for research protocols involving the potential for life-threatening reactions.

These guidelines are intended to reduce the potential for serious or life-threatening reactions when clinical research is conducted. The following issues were addressed: identifying the risks involved in the research, providing adequate safeguards in the protocol design and during withholding of medication, anticipating risks, minimizing the chances for human error, providing resuscitative equipment sufficient to deal with the most serious anticipated life-threatening reactions, planning for medical support in case of a life-threatening emergency, and optimizing the use of medical personnel and expertise to handle emergency situations. The guidelines also discuss important general issues about protocol design and implementation and the human subject consent form, which should facilitate the approval of protocols by the governing institutional review board. The guidelines are not meant to be inflexible or applicable to all research situations. However, it is our hope that they will allow for clinical research to be conducted in a manner that affords the research subjects a high degree of protection from unnecessary and possibly fatal injuries.

Bronchi↗

Oestrogen and cyclical progestogen in postmenopausal hormone replacement therapy.

OBJECTIVE: To ascertain the effectiveness, safety and incidence of side effects of a postmenopausal hormone replacement regimen consisting of continuous conjugated equine oestrogens and cyclical medroxyprogesterone acetate given for the first 14 days of each calendar month. DESIGN: A six month, prospective, open label, two centre, outpatient study of continuous Premarin (0.625 mg; Wyeth-Ayerst) and cyclical Provera (10 mg; Upjohn). Dosage adjustment was allowed in one centre. STUDY POPULATION: Seventy-six postmenopausal women in Adelaide and Brisbane. MAIN OUTCOME MEASURES: Menopausal symptom score, serum lipid levels, routine biochemical and haematological indices, endometrial histology and clinical bleeding pattern, blood pressure, weight changes, side effects, withdrawal from the study, compliance and necessary dose adjustment. MAIN RESULTS: Eight women withdrew from the study and nearly 50% experienced some minor side effect. Where dosage adjustment was allowed, almost all side effects were eliminated. Most patients had acceptable regular withdrawal bleeds although some were deemed heavy. There was a statistically highly significant 54% reduction in the menopausal symptoms score at three months and a 62% reduction at six months. Endometrial biopsy at six months showed atrophic or secretory endometrium with no inappropriate proliferation or hyperplasia. Total cholesterol and low density lipoprotein (LDL) cholesterol levels were significantly decreased. The high density lipoprotein (HDL) cholesterol level remained unchanged and triglyceride levels were raised within the normal range. There were no other clinically relevant biochemical, haematological or clinical changes. CONCLUSION: Continuous conjugated equine oestrogens (0.625 mg) and cyclical medroxyprogesterone acetate (10 mg) for the first 14 days of each calendar month proved to be a safe and effective postmenopausal therapy regimen. Initial minor side effects were common but could be readily ameliorated with early follow-up and dose titration.

Adult↗

Immunoassay of tryptase from human mast cells.

A sandwich ELISA was developed for the measurement of tryptase. The assay utilizes the mouse monoclonal anti-tryptase antibody, termed G5 (IgG2b kappa) in the solid phase and monospecific goat IgG anti-tryptase antibody together with tryptase in the fluid phase. The immunoassay will quantify 0.1 ng-5.6 ng of tryptase per 100 microliters of sample solution to within 0.1 ng. Intra-assay coefficients of variation were determined at 0.3 ng, 1.0 ng and 3.0 ng of tryptase per assay, respectively, to be 19%, 7% and 4% with buffer and 10%, 4%, and 4% in the presence of 20% plasma. Inter-assay coefficients of variation at the same respective levels of tryptase were 22%, 18% and 15% with buffer and 18%, 11% and 14% with 20% plasma. Net absorbance values obtained with a standard amount of tryptase in buffer alone and up to 50% (v/v) normal human citrate-treated plasma were within 10% of one another, indicating nearly complete detection of tryptase added to plasma. This represents the first sensitive immunoassay for a preformed mediator specific for human mast cells.

Antibodies, Monoclonal↗

Fibronectin turnover in human mesangial cell cultures as affected by adriamycin.

Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2 +/- 0.3% of total protein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5-5 micrograms/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 micrograms/ml (7.3 +/- 2.3 pg/cell vs. controls: 4.4 +/- 1.9 pg/cell; n = 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 micrograms ADR/ml. In accordance, immunofluorescence staining revealed an expansion of pericellular FN fibers in cultures exposed to 2 micrograms ADR/ml. Concomitant with the accumulation of extracellular FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium of ADR-treated HMC. These data suggest that ADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.

Cells, Cultured↗