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Biomedical subjects

G L Rose

Publications and source records attributed to G L Rose.

11 recordsLinked to original sources
PubMed1995

Updating the clinical experience in endometriosis--the European perspective.

In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group.

Danazol↗
PubMed1988

The inhibitory effects of danazol, danazol metabolites, gestrinone, and testosterone on the growth of human endometrial cells in vitro.

Danazol and gestrinone are effective drugs in the treatment of endometriosis. Their mechanism of action remains uncertain, but may be related to their androgenic activity. The authors examined the effect of danazol on human endometrial cells cultured in vitro, its two major metabolites, ethisterone and 2 hydroxymethyl ethisterone, gestrinone, and testosterone (T) at 1X and 10X expected plasma concentrations. Danazol and T suppressed growth by 20.8 and 25.0% (P less than 0.01), respectively, at the lower dose, and by 26.9 and 35.5% (P less than 0.01), respectively, at the 10-fold higher dose. No significant suppression of growth occurred with gestrinone, ethisterone, or 2 hydroxymethyl ethisterone. The results provide further evidence that danazol and T (but not gestrinone) may act by a direct effect on endometrial tissue.

Cell Division↗
PubMed1986

A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo.

Danazol and gestrinone are both effective agents in the treatment of endometriosis. Their mechanism of action is unknown but may be related to their androgenic activity, which is at least partly dependent on increases in the proportion of testosterone which circulates unbound to plasma protein. We have quantified these increases in patients on treatment, and by experimentation in vitro have demonstrated the relative importance of the reduction of sex hormone binding globulin (SHBG) binding capacity and competition with testosterone for SHBG binding sites by the drugs and some of their metabolites. The mean SHBG binding capacity in patients treated with danazol (400 mg/d, n = 7) and gestrinone (5 mg/week, n = 7) fell from 66.9 and 56.4 nmol/l to 36.1 and 28.1 nmol/l, after 1 week's treatment and to 11.1 and 7.1 nmol/l after 4 weeks respectively. Despite the similarity between the falls in SHBG binding capacity there was a significantly greater increase in % free testosterone in plasma samples from patients treated with danazol than in those from patients treated with gestrinone at 1 week. Experiments in vitro suggest that this was largely due to ethisterone (a major metabolite of danazol) competing with testosterone for SHBG binding sites. After 4 weeks on treatment there was a similar, near maximal reduction in SHBG binding of testosterone in both treatment groups. At the low levels of SHBG binding capacity reached by this time the extra effect of any competition for binding sites was much reduced.

Danazol↗
PubMed1986

Dosage-related effects of danazol on sex hormone binding globulin and free and total androgen levels.

Danazol is known to cause marked suppression of sex hormone binding globulin (SHBG) levels in plasma and to increase the proportion of plasma testosterone unbound to protein but the effect on the concentration of total and free testosterone is unclear. Twenty-five patients with endometriosis were treated daily for 6 months with doses of danazol ranging from 50 to 600 mg. The fall in SHBG and rise in percent free testosterone was dose-related during the early part of treatment. Suppression of total testosterone and 5 alpha-dihydrotestosterone levels occurred and was probably due to increases in metabolic clearance rates. The observed fall in androstenedione levels was related to the incidence of menstrual abnormality, suggesting that this might be due to reduced ovarian activity. The concentration of free testosterone increased by a factor of two in the first week but subsequently returned to levels of between 25 and 50% above pretreatment levels. This pattern of changes may be due to the rise in metabolic clearance rates being dependent on induction of enzymes of androgen metabolism.

Clinical Trials as Topic↗
PubMed1986

Aetiological factors in placenta praevia--a case controlled study.

The obstetric and gynaecological histories of 80 women with proven placenta praevia have been reviewed together with case controls matched for age and parity. There was a significant relation between placenta praevia and previous caesarean section (P less than 0.05), dilatation and curettage (P less than 0.01), spontaneous abortion (P less than 0.05) and evacuation of retained products of conception (P less than 0.05). Repeated uterine instrumentation was associated with increased risk of placenta praevia (P less than 0.001). We were unable to show any influence of previous termination of pregnancy. These findings are consistent with the hypothesis that endometrial/myometrium damage is a significant aetiological factor in low placental implantation.

Abortion, Induced↗
PubMed1982

A self-inflating tissue expander.

Tissue expansion is a means of mechanically creating an excess of soft tissue, contiguous to a defect, for use in reconstruction. To accomplish this, a self-inflating implant has been designed, tested, and used clinically. It offers potential advantages over similar percutaneously inflated devices, but has also presented new problems. Histologically, tissue expansion in the guinea pig is relatively innocuous, utilizing this implant; clinical results were similarly encouraging. Further clinical studies and applications await the identification of a more permeable membrane.

Adolescent↗
PubMed1981

Comparison of lung diffusing capacity during rebreathing and during slow exhalation.

In five normal sitting subjects DLCO and Qc were measured from the disappearances of a stable isotope of carbon monoxide (C18O) and of acetylene with respect to an inert and insoluble reference gas (Helium). Measurements were made during two respiratory maneuvers: (1) during rebreathing both at functional residual capacity (FRC) and near total lung capacity (TLC); and (2) during a slow exhalation at a constant rate from TLC to FRC. Changes in gas concentration were measured at the mouth during both maneuvers with a respiratory mass spectrometer. Mean DLCO was significantly higher during rebreathing near TLC (34.6 ml . min-1 . mm Hg-1) than near FRC (28.8 ml . min-1 . mm Hg). Mean DLCO measured during slow exhalation near FRC (32.7 ml . min-1 . mm Hg) was significantly higher than DLCO measured during rebreathing over the same volume range. Measurements of Qc were not significantly different between the rebreathing and slow exhalation maneuvers. Differences in DLCO between the two methods at FRC were not due to differences in Qc.

Adult↗
PubMed1980

Hysteresis in the relation between diffusing capacity of the lung and lung volume.

The diffusing capacity of the lung for carbon monoxide (DLCO) varies directly with lung volume (VA) when measured during a breath-holding interval. DLCO measured during a slow exhalation from total lung capacity (TLC) to functional residual capacity (FRC) does not vary as VA changes. Since VA is reached by inhaling during breath holding and by exhaling during the slow exhalation maneuver, we hypothesized that the variability in the relation between DLCO and VA was due to hysteresis. To test this hypothesis, breath-holding measurements of DLCO were made at three lung volumes, both when VA was reached by inhaling from residual volume (RV) and when Va was reached by exhaling from TLC. At 72% TLC, DLCO was 22% higher when VA was reached by exhalation compared to inhalation (P < 0.02). At 52% TLC, DLCO was 19% higher when VA was reached by exhalation compared to exhalation (P < 0.005). DCLO measured during a slow exhalation fell on the exhalation limb of the CLCO/VA curve. these data indicate that there is hysteresis in DLCO with respect to lung volume.

Adult↗
PubMed1979

Diffusing capacity at different lung volumes during breath holding and rebreathing.

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.

Adult↗