The rise in obstetric intervention with maternal age: a continuous phenomenon.

Population-based data from the Cardiff Births Survey has been used to examine the trends in obstetric intervention with increasing maternal age. As maternal age increases, spontaneous vaginal delivery rates fall, instrumental delivery rates, elective and emergency caesarean section, induction of labour and epidural rates rise. Induction of labour and epidural in labour are both associated with decreased spontaneous vaginal delivery rates and an increase in instrumental delivery rates and emergency caesarean section.

Cortical remodeling following suppression of endogenous estrogen with analogs of gonadotrophin releasing hormone.

The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 microns (p = 0.0089) and also the number of osteons with diameters over 250 microns (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p < 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.

The effect of add-back treatment with tibolone (Livial) on patients treated with the gonadotropin-releasing hormone agonist triptorelin (Decapeptyl).

OBJECTIVE: To assess whether tibolone can prevent the bone loss and symptomatic side effects normally associated with GnRH agonist (GnRH-a) use and whether tibolone modifies the effect of GnRH-a on endometriosis. DESIGN: Prospective, double-blind, placebo-controlled, group comparative study. SETTING: Gynecological research unit in a London teaching hospital. PATIENTS: Twenty-nine patients with endometriosis and two with fibroids. INTERVENTIONS: Six months of treatment with 3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg tibolone. MAIN OUTCOME MEASURES: Daily symptom diary for hot flushes and bleeding episodes, laparoscopic scoring of endometriosis, endocrine and biochemical changes, and bone mineral density scans. RESULTS: Lumbar spine bone mineral density decreased significantly from baseline in the placebo group (-5.1%) but not in the tibolone group (-1.1%). The frequency of hot flushes and sweating episodes was reduced significantly by tibolone. There was no difference between the two treatment groups with regard to the endometriosis scores. CONCLUSIONS: The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor symptoms that normally occur with GnRH-a, thus making long-term treatment with GnRH-a safer and more acceptable. It does not negate the therapeutic effect of GnRH-a on endometriosis.

The effects of gonadotrophin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis.

The administration of gonadotrophin-releasing hormone (GnRH) analogs to premenopausal women causes hypoestrogenism and bone loss, but the effects on cancellous microstructure have not been determined. In this study we have assessed bone structure in transiliac biopsies obtained from women before and after treatment for endometriosis with GnRH analogs. Twenty-one premenopausal women were studied, paired biopsies being obtained in 13; five women received both GnRH analogs and Org OD 14 (Tibolone, Livial). Comparison of pre- and post-treatment biopsies in women treated only with GnRH analogs showed a reduction in indices related to connectivity (node-to-terminus ratio, node-to-loop strut length, p < 0.02) and increase in inversely related indices (terminus-to-terminus and node-to-terminus strut length, p < 0.03). No significant changes were seen in any of the structural indices in women receiving both GnRH and Org OD 14 therapy. Activation frequency and bone formation rate at tissue level increased in women treated with GnRH agonists alone, although this change was not statistically significant. Our results suggest that bone loss induced by GnRH analogs may be associated with adverse effects on cancellous microstructure which are unlikely to be reversed following cessation of therapy. Concurrent treatment with Org OD 14 appears to prevent these changes.

Fluctuation of mineral apposition rate at individual bone-remodeling sites in human iliac cancellous bone: independent correlations with osteoid width and osteoblastic alkaline phosphatase activity.

We investigated the determinants of bone formation at individual remodeling sites (BMUs) in cancellous bone from 8 osteologically normal, sex hormone-replete women with endometriosis. All were tetracycline double-labeled (2, 12, 2, and 4 day regime) before iliac bone biopsy. At each BMU the mineral apposition rate (MAR) was determined conventionally from the distance between label midpoints (MAR 1) and also from the distance between the mineralization front and the trailing edge of the second label (MAR 2). MAR 1 and 2 were compared with within-BMU measurements of osteoid width (O.Wi) and the activities of osteoblastic alkaline phosphatase (AP) and succinic dehydrogenase (SDH, an enzyme in the Krebs cycle), both quantitated by microdensitometry. A total of 143 BMUs were evaluated, of which 88 were satisfactory for all measurements and 132 were satisfactory for all but SDH. There was a weak correlation (r = 0.34) between MAR 1 and 2 at individual sites, with a mean difference of 0.49 micron/day (mean MAR 0.82 micron/day). The mean MAR of individual subjects tended to be either increasing or decreasing (F = 16.1, p < 0.01). In linear regressions, MAR 2 was statistically dependent on O.Wi, AP, and SDH (73% of the variance accounted for). In contrast, MAR 1 was weakly correlated with O.Wi and only 30% of its variance was accounted for by AP, SDH, and O.Wi. The variance in the MAR 2 data was inversely increased (p < 0.01) compared with MAR 1 as the number of days of bone formation represented.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis.

OBJECTIVE: To compare dydrogesterone with placebos in the treatment of minimal to mild endometriosis. DESIGN: Prospective, double-blind, randomized study. SETTING: Three Obstetrics and Gynaecology Departments in the United Kingdom. PATIENTS: Sixty-two premenopausal women with complaints of pain (n = 12) and infertility with or without pain (n = 50) with minimal to mild endometriosis diagnosed at laparoscopy. Thirty-nine women had a laparoscopy after treatment and 56 women were followed up 12 months after treatment. INTERVENTIONS: Two high doses of dydrogesterone (either 40 or 60 mg) or a placebo, which was given for 12 days, beginning 2 days after the LH surge for a treatment period of 6 months. MAIN OUTCOME MEASURES: Change between before and after treatment endometriosis scores, pregnancy rates (PRs), and pain. RESULTS: Treatment with dydrogesterone did not alter the natural history of endometriosis or PRs when compared with placebo. Pain was reduced significantly during treatment with 60 mg dydrogesterone and this improvement still was evident at 12-month follow-up. CONCLUSION: Luteal phase dydrogesterone reduces pain associated with endometriosis.

Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone.

It is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to -70 degrees C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by greater than or equal to 1 lamella of osteoid and greater than or equal to 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (kappa statistic, range 0.71-1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which greater than 3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP-positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP-positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level).(ABSTRACT TRUNCATED AT 250 WORDS)

Patient-recorded domiciliary fetal monitoring.

Domiciliary fetal monitoring via a telephone link has been in clinical use at the Royal Free Hospital for 2 years, during which time 858 traces of 134 patients who were moderately at risk have been transmitted to the hospital. All recognized abnormal heart rate patterns were detected during the study period. In seven patients obstetric intervention took place on the basis of the domiciliary fetal monitoring recording and subsequent hospital monitoring. There were no intrauterine or neonatal deaths, and there was no overall increase in obstetric operative intervention. There appeared to be a significant reduction in the inconvenience suffered by the patient and her family, compared with conventional monitoring. Fetal heart recordings performed solely by the patient were of a high quality and reduced the demand on midwifery resources. To allow this only 3 hours of midwifery time daily was required and no additional demands on obstetric staff were made. It is anticipated that domiciliary fetal monitoring, performed by patients, will become an essential and established service throughout the United Kingdom (and probably Europe) as the principal means of monitoring fetal well-being.

Gastric leiomyosarcoma: clinical and pathological review of fifty patients.

Fifty patients with gastric leiomyosarcoma seen at M.D. Anderson Hospital between 1957 and 1978 were reviewed. Symptoms included weakness, gastrointestinal bleeding, and epigastric pain. An upper abdominal mass or tenderness was the most frequent physical finding. Laparotomy was performed in all patients, with gastric resection in 86%, and resection for cure in 68%. Survival after distal subtotal gastric resection (mean: 62 months) was longer than after proximal subtotal (30 months) or wedge resection (46 months). The five-year survival was 19% for all patients, and 32% for those operated on for cure. A favorable prognosis was predicted by mild atypia or few mitoses (grade 1). No differences in survival were demonstrated between patients with tumors of different cell types (epithelioid, spindle, or pleomorphic). No lymph node in any patient contained metastatic tumor, suggesting a lymph node dissection need not be performed. Commonly, tumor spread was to liver or lungs or by direct invasion of contiguous tissue or organ. Radiotherapy and chemotherapy are of limited value in treating unresectable disease. If possible, both the primary lesion and recurrent tumor should be widely resected.