The effect of diet and insulin on metabolic profiles of women with gestational diabetes mellitus.

Twenty women with abnormal glucose tolerance, detected from a routine program of antenatal screening for gestational diabetes mellitus (GDM) at 28 wk, were admitted for 24-h metabolic profiles. They were then alternately allocated to either insulin and dietary restriction or dietary restriction alone and then retested 4 wk later while on therapy. Ten normal controls were assessed twice at similar gestations to the study group. Before treatment, the 20 gestational diabetic subjects had higher mean concentrations of plasma glucose and 3-hydroxybutyrate than the controls for most of the profile, but mean insulin values were similar. Insulin therapy was associated with a reduction in mean glucose concentrations so that the profile was similar to the controls, while in the diet-alone group the reduction was less. The 3-hydroxybutyrate concentrations rose between profiles in the normal group and also rose in those treated by diet alone, but still remained within the upper range of normal even at night. Insulin therapy resulted in a similar 3-hydroxybutyrate profile to the controls. The C-peptide response to breakfast was reduced in both groups to levels below that of the controls. Neonatal outcome indices were similar in the two treatment groups, despite the differences in maternal metabolites, but because of the size of this study, conclusions about the neonate must be tentative.

Calorie restriction for treatment of gestational diabetes.

Birth weights of infants of 35 gestational diabetic mothers treated with calorie restriction alone (1200-1800 kcal) were compared with those of infants of 2337 nondiabetic women, including two control groups (A and B) matched for race, body mass index, age, and parity. All women were screened for gestational diabetes with the O'Sullivan screening method, and a 3-h oral glucose tolerance test was performed on all abnormal results. Control group A mothers had a normal screen, and control group B mothers had an abnormal screen with a normal glucose tolerance test. Pregnancy weight gain was significantly less for the gestational diabetic mothers (mean +/- SD 4.6 +/- 4.9 kg) than for the general prenatal population (9.3 +/- 5.3 kg), group A control subjects (9.7 +/- 5.3 kg), and group B control subjects (9.7 +/- 5.4 kg; P less than 0.0005). No infant of a gestational diabetic mother was below the 10th percentile for weight, and birth weights were similar to those of the control groups even though weight gain after the 28th wk of gestation was only 1.7 +/- 1.6 kg. The frequency of macrosomia (birth weight greater than or equal to 4000 g) was similar among the gestational diabetic mothers (9.3%), the general prenatal population (7.4%), and group A mothers (11.6%) but significantly higher for the group B control subjects (20.9%; chi 2 = 8.57, P less than 0.005). This study demonstrated that gestational diabetic mothers who are calorie restricted have infants with normal birth weights and a frequency of macrosomia less than that of screen-positive nondiabetic women with similar macrosomic risk factors.

Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries.

The aim of this study was to examine the hypothesis that hypersecretion of ovarian androgens in polycystic ovary syndrome results from an intrinsic abnormality of androgen biosynthesis by thecal cells. Steroid accumulation by human thecal cells from normal and polycystic ovaries (PCO-theca) was examined under basal and LH-stimulated conditions. A method for dispersing and culturing human thecal cells as primary monolayers in serum-free medium was developed. LH increased androstenedione (A), progesterone (P), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, and estradiol accumulation in the overlying medium in a dose-dependent manner at a maximum effective dose of 2.5 ng/mL. The principal variables affecting the magnitude of steroid accumulation were plating density, duration of incubation, and follicle size. Using only theca from follicles less than 10 mm and keeping plating density constant, 48-h steroid production by theca from five normal ovaries was compared to that from nine polycystic ovaries isolated from both anovulatory and ovulatory women. There was a significant increase in both basal (median, 32.1 pmol/1000 cells.48 h; range, 18.7-250) and LH-stimulated (56 pmol/1000 cells; range, 40.7-406) A accumulation by PCO-theca compared to basal (1.7 pmol/1000 cells; range, 1.1-4.3) and LH-stimulated (2.8 pmol/1000 cells; range, 2.0-8.1) A accumulation by normal theca, with no overlap in values between the two. Although P production was also increased in the PCO-theca, the A to P ratios under both basal and LH-stimulated conditions were significantly higher in the PCO-theca [A/P ratio normal; PCO basal, 0.1 and 0.53 (P < 0.01); LH-stimulated, 0.04 and 0.65 (P < 0.001)], suggesting increased conversion of P to A. The steroid response to LH was similar in both groups. This is the first report of a difference in thecal androgen production between normal and polycystic ovaries and supports the hypothesis that there is a primary abnormality in the regulation of androgen production in PCOS.

Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid.

The underlying cause of anovulation in polycystic ovary syndrome is unknown. Circulating levels of immuno- and bioactive FSH are within the normal range, and the follicles contain measurable levels of bioactive FSH. The aim of this study was to compare estradiol (E2) production in response to FSH by granulosa cells from normal ovaries with those from polycystic ovaries derived from both anovulatory (anovPCO) and ovulatory subjects (ovPCO). Intrafollicular levels of immunoactive FSH, E2, and androstenedione in follicles of less than 12 mm were also measured. Follicular fluid steroid concentrations were obtained from 41 pairs of normal ovaries and 23 pairs of polycystic ovaries (8 anovPCO and 15 ovPCO). In size-matched follicles from each group there were no significant differences in follicular fluid FSH or E2 concentrations, but androstenedione levels were significantly higher in 5- to 11-mm follicles from ovPCO than in corresponding follicles from normal ovaries. Dose responses to FSH were determined in granulosa cells derived from 9 pairs of normal ovaries, 7 anovPCO, and 8 ovPCO. Cells from anovPCO produced 6- to 10-fold more E2 in response to FSH than normal cells, although there was no significant difference in the ED50 values. The response in cells from ovPCO was reduced compared to normal, but this difference did not reach significance. In summary, as judged by their FSH and E2 contents, polycystic ovaries do not have a higher proportion of atretic follicles than normal. Indeed, cells from anovPCO are hyperesponsive to FSH in vitro. This could be explained by stimulation of aromatase in vivo by either paracrine or, more probably, by endocrine factors, of which insulin is an arguable candidate.

Direct gonadotrophic effect of growth hormone on oestradiol production by human granulosa cells in vitro.

In-vitro studies in both rodents and man suggest that GH can stimulate ovarian steroidogenesis, but it is not clear whether this effect is mediated by changes in circulating concentrations of insulin-like growth factor-1 (IGF-1) or whether it is a direct action on the ovary (or, indeed, both). In this study the effects of biosynthetic human GH (hGH) on the production of oestradiol and IGF-1 by human granulosa cells in culture were examined using ovarian tissue (from both normal and polycystic ovaries) which had not previously been exposed to exogenous gonadotrophin therapy. Addition of hGH (1 or 10 ng/ml) to the incubation medium resulted in a significant (1.7 to 3.6 fold) increase in oestradiol accumulation after 48h in culture. Human GH also had a significant additive effect on the dose-related responsiveness of granulosa cell oestradiol production to hFSH. Concentrations of IGF-1 in the medium were undetectable in each of these experiments. These studies demonstrate that hGH has a potent, direct stimulatory effect on production of oestradiol by the human ovary which is independent of the effect of FSH. These findings have important implications for understanding the physiological role of hGH in human ovarian function as well as for therapeutic use of biosynthetic hGH for induction of ovulation.

Glucose production by the human placenta in vivo.

The human placenta transports glucose by facilitated diffusion down a concentration gradient from mother to fetus. It has previously been considered incapable of glucose synthesis. However, recent work has demonstrated the presence in placental tissue of glucose-6-phosphatase, which is required for the final step in the synthesis of glucose. Following continuous intravenous infusion into the maternal circulation of the stable isotope, 6,6-(2)H(2)glucose, during elective caesarean section, we have observed isotope dilution in the umbilical vein, without further dilution in the umbilical artery. Using a mathematical model containing maternal, placental and fetal compartments, the data were compatible with the release of glucose by the placenta. We conclude that the human placenta at term can produce glucose.

Substance P: endothelial localization and pharmacology in the human ovarian vein.

OBJECTIVE: To investigate the possible role of substance P as an endothelial factor in the local regulation of vascular tone in the human ovarian vein. METHODS: We performed immunolocalization of substance P in human ovarian venous endothelium in situ and in culture, and observed responses to substance P in preconstricted ring preparations of human ovarian vein in the presence of either the prostaglandin synthesis inhibitor indomethacin or the inhibitor of nitric oxide synthesis L-nitro arginine methyl ester (L-NAME), with and without luminal rubbing. RESULTS: Substance P was localized in a subpopulation of ovarian vein endothelial cells. Maximal relaxation induced by substance P was not significantly affected by indomethacin (10 mumol/L), but was reduced from 58.7% (95% confidence interval [CI] 41.3-76.1) in control experiments to 24.7% (95% CI 18.3-31.1) after luminal rubbing and to 32.3% (95% CI 19.8-44.8) after exposure to L-NAME (0.1 mmol/L) (P = .001). CONCLUSION: The localization of substance P in ovarian vein endothelium together with vasodilator effects mediated partially via the endothelium suggests that the peptide has a role in the local control of vascular tone in this vessel.

Interrelationships among abnormal cardiotocograms in labor, meconium staining of the amniotic fluid, arterial cord blood pH, and Apgar scores.

A prospective study of the relationships among fetal heart rate pattern, meconium staining of the amniotic fluid, umbilical cord artery pH, and Apgar score was carried out in 1219 consecutive births. Interpretable cardiotocogram patterns and cord arterial pH and blood gas analysis were obtained in 698 cases. The sensitivity of an abnormal cardiotocogram at any time for acidosis (more than 1 SD below the mean, pH less than 7.17) was 80%, and for severe acidosis (more than 2 SDs below the mean, pH less than 7.085) was 83%. However, the predictive value was low, and 32% of fetuses had an abnormal cardiotocogram but no acidosis. If only cardiotocogram abnormality in the first stage of labor was considered, sensitivity was still 47% for acidosis and 67% for severe acidosis, and the false-positive rate was reduced to only 14%. We attempted to improve the prediction of acidosis by including meconium staining of the amniotic fluid, but 65% of the variation in umbilical cord artery pH and 72 and 86% of the variation in 1- and 5-minute Apgar scores, respectively, remained unexplained. In light of these poor correlations, the current practice of considering cardiotocogram abnormality, meconium staining of the amniotic fluid, acidosis, and low Apgar scores as indicating one single disorder, "fetal distress," is not valid.

Reliability of endometrial aspiration cytology in the assessment of endometrial status.

One hundred twenty women attending routine gynecologic clinics were investigated by endometrial aspiration cytology to determine whether outpatient assessment of endometrial status could be used to determine subsequent patient management. The results show that this technique allows recognition and distinction between cystic hyperplasia, adenomatous hyperplasia, and carcinoma, and the time of the menstrual cycle can be assessed when the endometrium is normal. Endometrial aspiration cytology is valuable in gynecologic practice for determining which women with abnormal bleeding, both premenopausal and postmenopausal, require further investigation. Furthermore, the technique has a role to play in monitoring the status of the endometrium in women at high risk of endometrial malignancy, particularly those receiving hormone replacement therapy.

Factors predisposing to and outcome of gestational diabetes.

Two hundred thirteen women with abnormal glucose tolerance tests (GTTs) were diagnosed over 9 years by a screening program involving the total antenatal population. Each subject was matched for age, parity, and ethnic group with a control. The gestational diabetics were subdivided into classes A1 or A2 based on the fasting plasma glucose value of their GTT: A1 when below 6.0 mmol/L (108 mg/dL) and A2 when 6.0 mmol/L (108 mg/dL) or higher. All received treatment with dietary advice and some with insulin. Birth weight was not related to maternal age or severity of diabetes, but was related to maternal obesity. However, neonatal morbidity indices such as admission to the special care baby unit for longer than 48 hours and polycythemia (hematocrit above 65%) were related significantly to the severity of the diabetes and not to maternal age or obesity.

What is the optimal caesarean section rate? An outcome based study of existing variation.

STUDY OBJECTIVE: To investigate the consequences of different levels of caesarean section (CS) rate in terms of fetal and maternal outcomes. DESIGN: Comparison of outcome variables between four categories of maternity units stratified according to CS rates. Data were collected concurrently. SETTINGS: All 17 maternity units in one health region. SUBJECTS: Data for the perinatal mortality analysis: all 221,867 deliveries in 1983-87 (excluding severe malformations) (1462 deaths); maternity information analysis system: all 36,727 women with singleton pregnancies who delivered in 1988. OUTCOME MEASURES: Perinatal mortality, Apgar scores at one and five minutes, onset of respiration after one minute, postnatal transfusion, postnatal infection, thromboembolism, low haemoglobin concentration at discharge, and puerperal psychosis were determined. RESULTS: Teaching hospitals with an increased proportion of high risk cases had the highest CS rate, but the other three categories were found to serve comparable populations. Perinatal mortality showed a birthweight specific pattern--for very low birthweight infants, but not for other deliveries, mortality rates were lower in units with higher CS rates. Apgar scores showed no trend, but the onset of respiration after one minute was significantly more frequent in units with a CS rate of less than 10%. Increased maternal postnatal blood transfusion was associated with higher CS rates but no trend was observed for the other maternal variables. CONCLUSIONS: CS rates in general maternity units should be 10 to 12% or lower in the singleton population as a whole, but a more interventionist approach is indicated for very low birthweight infants. If confirmed, these recommendations could easily be incorporated into clinical audit.

Remediation of pain-related memory bias as a result of recovery from chronic pain.

Cognitive biases are increasingly implicated as vulnerability factors in emotional and physical disorders. This issue is examined here in chronic pain sufferers using a recall memory paradigm. A sample of chronic pelvic pain patients undergoing hysterectomy and oophorectomy were assessed prior to the intervention, 8 weeks post-surgery, and again 6 months post-surgery. On each occasion patients were aurally presented four mixed lists of sensory, affective, neutral and gardening words, matched for frequency and length. No difference in the recall of neutral and gardening words was found, suggesting that selective memory for pain-related information cannot be attributed to superior recall of words belonging to a common semantic category. A clear pattern of more pain-related words being remembered before surgery, but better recall of non-pain-related words 6 months post-surgery when pain intensity ratings are significantly reduced, was evidenced. These results suggest that selective memory for pain-related words is more likely to be a secondary consequence of the long term experience of pain than a stable, enduring cognitive vulnerability factor.

Sociopsychological factors in chronic pelvic pain: a review.

Chronic pelvic pain is a common gynecological problem. There has long been an assumption that social and psychological factors play a part in its genesis in a significant subgroup, but their precise role remains unclear. More recently, childhood sexual abuse has been implicated as a specific risk factor. For this review, PSYCHLIT and MEDLINE searches for relevant publications were supplemented by tracing back through the latter's related reference lists. One hundred thirty-one references directly concerning pelvic pain were identified with varying emphasis on social and psychological aspects. A further 449 references were in related fields. Forty-three were considered to be helpful in directly exploring the link between chronic pelvic pain and sociopsychological factors and 22 of these reported specific studies directly relevant. In common with other research into chronic pain conditions, it appears unhelpful to separate this type of pain into "psychogenic" and "organic" categories. Clear case definition is essential. The specificity of childhood sexual abuse as a risk factor is unclear. It may be helpful to consider clearly defined subgroups with the condition in future studies. An example of such a subgroup with pelvic venous congestion is discussed.

Sociopsychological factors in women with chronic pelvic pain with and without pelvic venous congestion.

Social and psychological factors have long been proposed as being of importance in a sizeable subgroup of women complaining of unexplained chronic pelvic pain (CPP). The aim of this study was to examine this in two subgroups of CPP patients, thereby eliminating pain alone as the determining variable. Consecutive attenders at a clinic for CPP were assessed on a range of somatic, historical, social, and psychological variables using detailed interviews and questionnaires. They were subsequently allocated to one of two groups, based on the presence or absence of pelvic venous congestion (PVC). Significant associations emerged between some social arrangements, paternal parenting, and patterns of hostility in the group with pelvic venous congestion. The groups also differed in patterns of family illness, and the congested group tended to report more childhood sexual abuse (CSA). Clear case definition in CPP is important. In the subgroup with pelvic venous congestion early social experience may play an important role. Father-daughter relationships may be particularly relevant. Hostility patterns may influence the development of the condition. CSA does not appear to play a specific role in all unexplained CPP cases, but may have relevance for the subgroup with pelvic venous congestion.

Pelvic congestion in women: evaluation with transvaginal ultrasound and observation of venous pharmacology.

Fourteen women with chronic pelvic pain due to congestion underwent transvaginal ultrasound scanning to observe changes in the diameters of dilated pelvic veins. Spontaneous fluctuations were observed, and intravenous dihydroergotamine resulted in a consistent venoconstrictor response (p = 0.0021) during 20 min observation. Transvaginal ultrasound is useful for imaging dilated pelvic veins and for the study of venous pharmacology.

The future of obstetrics and gynaecology in Europe.

There is a general recognition that the health of women in Europe can be improved by collaboration between obstetricians and gynaecologists in EU and EFTA countries. The way in which collaborative approaches are developing are discussed, including the problems that have to be addressed if such an initiative is to be successful.

Pelvic pain--pelvic congestion or the irritable bowel syndrome?

Chronic unexplained pelvic pain in women may arise from either gynaecological or colonic causes. 35 women with pelvic congestion were interviewed with regard to their bowel habits and compared with a population with the irritable bowel syndrome. The results suggest that pelvic congestion and the irritable bowel syndrome are two distinctly different conditions, both of which may cause chronic lower abdominal pain in women.

Release of vasoactive agents from the isolated perfused human ovary.

OBJECTIVE: To investigate local vascular control in the isolated perfused premenopausal human ovary by measuring flow-induced release of vasoactive substances. DESIGN: Release of adenosine 5' triphosphate (ATP), substance P (SP), endothelin (ET), and vasopressin (AVP) from the ovarian vascular endothelium was estimated in perfusate under basal conditions and during two periods of increased flow. MAIN OUTCOME MEASURES: Vascular resistance; ATP, SP, ET and AVP release. RESULTS: The mean ratio (pressure/flow during increased flow):(pressure/flow at basal flow) was 1.27 +/- 0.04 for the first, and 1.15 +/- 0.05 for the second period of increased flow (n = 10), indicating significant vasoconstriction (P < 0.01 and 0.05, respectively), present to a greater extent during the first period of increased flow compared to the second (P < 0.05). ATP release was seen in response to increased flow (n = 8, P < 0.05). From 12 ovarian bed preparations, five released ET and SP and three of these released AVP. Four of the five perfused ovaries that released peptides contained either a developing follicle or a corpus luteum while all those that showed no peptide release were inactive. CONCLUSIONS: ATP release may play a role in the local control of the human premenopausal ovarian vasculature independent of ovulatory status. Peptides may also contribute to local vascular control in the ovary and their release from predominantly active ovaries suggests a relationship between ovulation and vascular endothelial function.

Correction of the non-uniform spatial sensitivity of electrical impedance tomography images.

One of the clinical applications of electrical impedance tomography (EIT) is the measurement of volume changes of body fluids. However, the spatial sensitivity of images produced by the Sheffield Mark I system is non-uniform and if quantitative comparisons of resistivity images resulting from volume changes are to be mad, this non-uniformity must be corrected for. All experimental data were collected from a phantom consisting of semi-permeable membrane tubes fixed vertically at different distances from the centre of a cylindrical tank which was filled with a saline solution of resistivity 5 omega m. Individual images were obtained when each tube was filled with a saline solution of resistivity 1.5 omega m. Analysis of these images, using the resistivity integral described by Thomas et al, yielded the sensitivity of EIT at different positions within the tank. Combinations of tubes were then filled with saline (1.5 omega m) and an image produced for each combination. Cross sections of the images were taken and used to confirm that the principle of superposition is valid for EIT. A simple pixel scaling correction, derived from the sensitivity data, was then applied to the images and the results re-analysed to demonstrate a reduction in volume measurement error. The application of this correction to in vivo images is discussed.

Management of women presenting to the accident and emergency department with lower abdominal pain.

The diagnosis and management of lower abdominal pain is difficult, particularly for the inexperienced accident and emergency (A&E) or surgical trainee. In women, potential gynaecological causes may further confuse the picture. We analysed the incidence, spectrum of presentation and immediate management of 322 women presenting consecutively to an inner city A&E department over a 6-month period with lower abdominal pain. A standard questionnaire relating to history, examination, immediate investigations and preliminary diagnosis was completed by the attending A&E doctor. The cause of abdominal pain, according to the A&E doctor's diagnosis, was gynaecological in 61%, gastroenterological in 23%, urological in 7% and non-specific in 9% of cases. Of the women, 39% (124/322) were referred to a duty specialist, of whom 86% (107/124) required admission for investigation and/or treatment. Women initially diagnosed as having pain of gynaecological origin formed the largest group of patients to be referred. In 69% (67/97) of these cases, the A&E doctor's initial diagnosis was confirmed by the gynaecologist. This study shows that pain of gynaecological origin was the largest single cause of lower abdominal pain in women presenting to our A&E department and that, in the majority of cases, these women needed to be referred to the duty gynaecologist for immediate treatment. Although overall diagnostic accuracy rate was relatively high, the management of potentially life-threatening gynaecological conditions such as ectopic pregnancy was poor. These results emphasise the need to improve in-service gynaecological training in A&E departments.