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Biomedical subjects

R W Beard

Publications and source records attributed to R W Beard.

At least 55 records · Page 3Linked to original sources
PubMed1994

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.

Adult↗
PubMed1994

The fine structure of the human ovarian vein.

The human ovarian vein is of particular interest as an adult vessel which changes with the different phases of reproductive life. At the ultrastructural level we have characterised the endothelium, vascular smooth muscle and autonomic innervation of the human ovarian vein. Transmission electron micrographs were prepared from surgical specimens of the human ovarian vein (n = 11) to demonstrate the features of the vessel wall. The pattern of innervation was investigated using an image analysis system which was also used with high-magnification micrographs to count and measure axonal vesicle types. Possible relationships between ultrastructural features and age and reproductive history were investigated. Endothelial cells contained Weibel-Palade bodies and numerous microfilaments. There were 3 muscle coats: no elastic lamina separated the endothelium from an inner layer of smooth muscle; a middle smooth muscle layer consisted of cells orientated in a circular fashion; an outer smooth muscle layer was made up of longitudinally arranged smooth muscle bundles with collagen and nerves penetrating throughout. The percentage of the vessel thickness occupied by the middle circular smooth muscle layer ranged from 0 to 33% and fell with increasing age (r = -0.67, P < 0.05). Penetration of nerves into the circular layer was observed only in 2 of 9 specimens. The observed ultrastructural features are consistent with the ability of the ovarian vein to distend substantially in response to changing circulatory demands. The vascular endothelium may have a role in the local control of haemostasis via the synthesis and storage of von Willebrand factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Gestational diabetes: a challenge for the future.

It is well established that pregnancy is associated with temporary changes in maternal metabolism which include a decrease in maternal insulin sensitivity to values similar to those associated with Type 2 diabetes. Fasting glucose concentrations fall throughout pregnancy, postprandial values rise. The maintenance of glucose tolerance in pregnancy requires a two- to three-fold increase in postprandial maternal insulin secretion. Glucose intolerance develops in women unable to compensate for the metabolic changes incurred by pregnancy. Increasing maternal hyperglycaemia is associated with increasing pregnancy morbidity and an increased likelihood of subsequent diabetes in the mother. In addition, maternal hyperglycaemia has a direct effect on the development of the fetal pancreas and is associated with an increased susceptibility to future diabetes in the infant, an effect which is independent of genetic factors. Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized in pregnancy, and by definition includes a small number of women with previously unrecognized diabetes or impaired glucose tolerance (IGT). Figures on the prevalence of GDM vary between maternity units, depending on screening methods and the ethnic distribution of the populations. However, in a comprehensive study of a multi-ethnic antenatal population in inner London, UK it was found that only 2% of pregnant women develop significant glucose intolerance. Obstetricians and physicians debate the importance of identifying this 2% of women. The lack of agreed criteria for diagnosing gestational diabetes and the questionable obstetric benefits of treating all women with mild disturbances of glucose tolerance in pregnancy has resulted in few UK centres undertaking universal screening for GDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Insulin insensitivity is associated with a decrease in postprandial thermogenesis in normal pregnancy.

Insulin sensitivity and postprandial thermogenesis were investigated at various stages of pregnancy to assess if changes in insulin sensitivity contribute to energy conservation during pregnancy. Cross-sectional and longitudinal studies were undertaken. Sixteen control non-pregnant women were compared with 10 women in the second trimester (2nd) and thirteen women in the third trimester (3rd) of uncomplicated pregnancy. Six women were studied at all three time points. The slope of plasma glucose decline following a bolus of intravenous insulin was used as an index of insulin sensitivity. Resting energy expenditure was measured with continuous indirect calorimetry. Postprandial thermogenesis was measured as the change in energy expenditure for the 2 h after a mixed meal. Results are expressed as mean +/- SEM or median (interquartile range). Insulin sensitivity was lower as pregnancy progressed (non-pregnant control 181 (177-205) vs 2nd 111 (100-112) vs 3rd 96 (80-109) mumol l-1 min-1, p < 0.001). Fasting insulin levels were significantly higher in the third trimester but not in the second trimester (non-pregnant control 1.9 (1.5-6.0) vs 2nd 3.1 (2.8-5.2) vs 3rd 8.6 (4.8-9.7) mU l-1, p < 0.05). Meal stimulated insulin levels were higher in the second and third trimesters compared to non-pregnant women (insulin area over 2 h, postmeal, non-pregnant control 78 +/- 10 vs 2nd 92 +/- 14 vs 3rd 145 +/- 14 mU l-1 h-1, p < 0.005). Postprandial thermogenesis was lowest in the third trimester (non-pregnant control 103 +/- 5 vs 2nd 74 +/- 8 vs 3rd 48 +/- 8 kJ, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

An alternative to hysterectomy? GnRH analogue combined with hormone replacement therapy.

OBJECTIVE: To assess whether GnRH analogues are effective in relieving pelvic pain and congestion and whether menopausal symptoms caused by GnRH analogues can be minimised by supplementation with low dose continuous combined hormone replacement therapy (HRT). DESIGN: Open prospective study. SETTING: Tertiary referral clinic at a teaching hospital. PATIENTS: Twenty-one women with chronic pelvic pain. INTERVENTION: Four months' therapy with goserelin 3.6 mg/month combined with continuous oestradiol valerate 1 mg daily and medroxyprogesterone acetate 5 mg daily. MAIN OUTCOME MEASURES: Visual analogue scale for pain, menopausal symptoms, bleeding patterns, uterine area, endometrial status, oestradiol concentrations and venogram scores. RESULTS: Amenorrhoea was maintained in all but two women. Endometrial atrophy was maintained despite HRT supplementation. Two women had moderate menopausal symptoms but none had severe symptoms. Significant reduction of uterine cross sectional area was maintained throughout the study. There was no significant relief of pain. CONCLUSIONS: HRT supplementation of GnRH analogues abolishes menopausal symptoms and thus may improve patient acceptability. Potentially beneficial effects such as endometrial atrophy, reduction of uterine volume and amenorrhoea were not negated by HRT. This combination is not effective in the treatment of chronic pelvic pain and congestion.

Adult↗
PubMed1993

Psychosocial aspects of chronic pelvic pain, with special reference to sexual abuse. A study of 164 women.

Patients with chronic pelvic pain attending a tertiary referral centre show certain social, developmental and psychological characteristics. Specifically, they appear to have fewer children and to report more paternal overprotection, and a trend towards low maternal care compared to normals. They also show more depression, free-floating anxiety and somatic anxiety than such populations. The levels are similar to those found in other outpatient populations presenting with migraine or irritable bowel syndrome. Hostility levels are greater than those in normal subjects. Overall the present patient population reports the same degree of childhood sexual abuse as do many other female clinic and community sample populations. Sexual abuse is unlikely to be a specific aetiological factor in the development of chronic pelvic pain though it may yet be found to be important in subsets of the population.

Adolescent↗
PubMed1992

Suprasensitivity to calcitonin gene-related peptide but not vasoactive intestinal peptide in women with chronic pelvic pain.

Chronic pelvic pain in women is associated with radiological evidence of pelvic venous dilatation and reduced flow, termed 'pelvic congestion'. The aim of this study was to elucidate a possible role in this condition for vasoactive intestinal peptide and calcitonin gene-related peptide, both localized in perivascular nerves in the ovaries and uterus. Healthy volunteers and women with chronic pelvic pain and venous congestion received intravenous infusions of vasoactive intestinal peptide (n = 15), calcitonin gene-related peptide (n = 15) or a bland infusate (n = 7). Changes in the uterovaginal and skin blood flow were assessed by continuous measurement of vaginal, axillary, cheek and hand temperature. During calcitonin gene-related peptide infusion median hand temperature changes were +0.97 degrees C in women with pelvic pain and -0.03 degrees C in healthy volunteers (p < 0.05). There were no differences between groups in hand and cheek temperature responses to vasoactive intestinal peptide infusion. Vasoactive intestinal peptide and calcitonin gene-related peptide appeared to dilate the uterovaginal vasculature in healthy subjects but not in those with pelvic pain. Vasoactive intestinal peptide and calcitonin gene-related peptide did not provoke pain in healthy subjects but in those with pelvic pain, symptoms were significantly exacerbated during calcitonin gene-related peptide infusion but not by vasoactive intestinal peptide. Changes in plasma follicle stimulating hormone, luteinizing hormone and oestradiol during either infusion were not significant. These findings indicate greater sensitivity to calcitonin gene-related peptide in women with pelvic pain and suggest a possible underlying neurovascular disorder.

Adult↗
PubMed1992

Measurement of pelvic blood flow changes in response to posture in normal subjects and in women with pelvic pain owing to congestion by using a thermal technique.

1. A method is described for studying pelvic blood flow in women by the indirect method of measuring vaginal temperature changes in response to a posture change. Ten women with chronic pelvic pain and venous congestion and 10 normal subjects were observed during posture changes over a 2 h period. 2. Vaginal temperature minus axillary temperature rose after subjects changed from the supine to the seated position, indicating a fall in the rate of pelvic blood flow. 3. A significantly greater variance in the rate of change in vaginal temperature minus axillary temperature was found in patients with pelvic venous congestion compared with control subjects (P less than 0.005). 4. The findings are consistent with a disorder of blood flow regulation in women with pelvic pain owing to congestion.

Adult↗
PubMed1992

Ethnic differences in insulin secretion in women at risk of future diabetes.

The plasma glucose and insulin responses to oral glucose were studied in 44 women who had previously had gestational diabetes, but had reverted to normal glucose tolerance. Twenty were White, 14 Black, and 10 Asian. A group of race-, age- and weight-matched controls was also studied. Fasting values of glucose and insulin did not differ significantly between the study group and controls. During the 2 h 75-g OGTT the White and Black previously gestational-diabetic women had similar plasma glucose values to their controls, while the Asian previously gestational-diabetic women had significantly higher glucose values at 30 min (9.2 +/- 0.6 (+/- SE) vs 7.1 +/- 0.3 mmol l-1, p less than 0.02) and at 60 min (8.6 +/- 0.8 vs 6.2 +/- 0.4 mmol l-1, p less than 0.02). Compared with their race-matched controls, the White previously gestational-diabetic women had significantly lower insulin values at 60 min (median 41 range 2-91) vs 56 (15-118) mU l-1, p less than 0.05), and the Black previously gestational-diabetic women had lower values at both 30 min (17 (4-116) vs 53 (22-197) mU l-1) and 60 min (36 (4-148) vs 99 (12-169) mU l-1, p less than 0.05). The insulin values were similar during the OGTT in the Asian previously gestational-diabetic women and their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

High prevalence of gestational diabetes in women from ethnic minority groups.

The influence of ethnic origin, body mass index, and parity on the frequency of gestational diabetes was assessed in 11,205 consecutive women attending a multiracial antenatal clinic in London, where all women were screened for gestational diabetes. Logistic regression was used to model the relationship between gestational diabetes and ethnic origin, age, body mass index (BMI), and parity. Results were presented as adjusted odds ratios, where the reference categories are White women, age < 25 years, BMI < 27, and parity < 3. Ethnic origin was the dominant influence on the prevalence of gestational diabetes. Women from ethnic groups other than White had a higher frequency of gestational diabetes than White women (2.9% vs 0.4%, p < 0.001). Compared to White women the relative risk of gestational diabetes in the other ethnic groups was: Black 3.1 (95% confidence limits 1.8-5.5), South East Asian 7.6 (4.1-14.1), Indian 11.3 (6.8-18.8), and miscellaneous 5.9 (3.5-9.9). Increasing age was an independent risk factor. The relative risk was higher in women > or = 35 years in all ethnic groups other than in South East Asian women. Obesity (BMI > or = 27) was a further independent risk factor in all ethnic groups except in the Indian and South East Asian women. Parity > or = 3 increased the relative risk of gestational diabetes in the White, Black, and South East Asian women only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

A longitudinal study of pelvic inflammatory disease.

OBJECTIVE: To study the microbiology and long term prognosis of pelvic inflammatory disease (PID). DESIGN: A prospective study of women with laparoscopically confirmed PID. SETTING: Teaching hospital in central London. SUBJECTS: 23 women with PID. OUTCOME MEASURES: Microbiological investigations at the time of diagnosis and at follow up; subsequent fertility and the occurrence of pelvic pain. RESULTS: PID diagnosed by laparoscopy was regarded as moderate to severe in 15 cases. Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum or a combination of these micro-organisms were detected most frequently in the cervix, less often in the endometrium and least in the tubes, C. trachomatis being the micro-organism found most commonly in the tubes. There was serological evidence of acute chlamydial infection in 13 of 20 cases in which paired sera were available and a serological response to M. hominis in 9 of 12 cases in which it was possible to evaluate the results. On the basis of microbiological and serological results, C. trachomatis appeared to be the most important aetiological agent in 10 cases, N. gonorrhoeae in four cases, M. hominis in three cases and U. urealyticum in none; in five cases, two of these micro-organisms appeared to be of equal importance. After 1 to 3 years, 33% of the women were having difficulty conceiving and 56% continued to complain of pelvic pain. CONCLUSION: It is difficult to be certain of the infectious cause of PID in any given case. However, the evidence that N. gonorrhoeae and C. trachomatis are pathogens is very strong. M. hominis may be responsible for a few cases on its own or together with other micro-organisms.

Cervix Uteri↗
PubMed1991

Cytogenetic studies of amniotic fluid taken before the 15th week of pregnancy for earlier prenatal diagnosis: a report of 114 consecutive cases.

One hundred and fourteen samples of amniotic fluid taken before 15 weeks of gestation were cultured for cytogenetic studies. The results of culturing these early amniotic fluid (EAF) samples were compared with the results of culturing 114 standard amniotic fluid (SAF) samples taken after 15 weeks of gestation matched for maternal age and received in the laboratory within the same week. Cell culture was successful in all 114 of the EAF samples and in 111 SAF samples. There was no significant difference in the days to harvesting and days to reporting in the two groups. Three samples of SAF failed to grow and two EAF samples produced tetraploid karyotypes, so that in these five cases amniocentesis had to be repeated. These problems were attributed to toxicity of a fungicide used in the culture medium. Pseudo-mosaicism was noted in two EAF samples and one SAF sample; and maternal cell contamination was noted in one EAF and one SAF sample. Thus, culturing and karyotyping cells harvested from EAF and SAF are similar, indicating that EAF samples from 12-14-week pregnancies could be used for prenatal diagnosis.

Adult↗
PubMed1991

Extraction of DNA from amniotic fluid cells for the early prenatal diagnosis of genetic disease.

Ten-ml samples of amniotic fluid were taken from pregnancies being terminated at 8-14 weeks' gestation. DNA was extracted from the amniotic cells by sequential centrifugation and analysed using the polymerase chain reaction (PCR). Fifteen samples were analysed for evidence of maternal contamination using Mfd5 oligonucleotide primers for repeat polymorphisms. Ten amniotic fluid samples were tested for the Delta-F508 deletion characteristic of cystic fibrosis to demonstrate a diagnostic application for the technique. In each case, DNA extracted from fetal tissue from the same pregnancy was included in the controls. In 14 of the 15 cases tested with the Mfd5 primers, both the amniotic fluid DNA and the fetal DNA showed no evidence of contaminating DNA. In one case, neither the amniotic fluid cells nor the fetal cells yielded results. In nine of the ten cases tested with the Delta-F508 primers, the amniotic fluid cell DNA provided accurate information about the genetic status of the fetus; in the tenth, the fetal DNA failed to amplify. The results indicate that adequate DNA can be extracted from amniotic fluid from 8 weeks' gestation onward and these samples are suitable for prenatal diagnosis using PCR.

Adult↗
PubMed1991

Early amniocentesis at 11-14 weeks' gestation for the diagnosis of fetal chromosomal abnormality--a clinical evaluation.

Early amniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained taps; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases (2.8 per cent). Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism. Of the 105 pregnancies successfully sampled, there have been two losses to date (1.8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes. Sixty-two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty-nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12. The results indicate that early amniocentesis may replace the traditional test at 15-17 weeks.

Adult↗
PubMed1991

A defect in insulin release in women at risk of future non-insulin-dependent diabetes.

1. A study on seven Caucasian glucose-tolerant women with previous gestational diabetes and seven matched control subjects is presented. The insulin response to oral glucose, insulin sensitivity and fasting glucose production rates were measured by using a 75 g oral glucose tolerance test, an insulin tolerance test and a non-radioactive tracer, [6,6-2H]glucose, respectively. 2. Fasting plasma glucose levels were similar between the women with previous gestational diabetes and the control subjects (4.8 +/- 0.3 versus 4.7 +/- 0.2 mmol/l), as were fasting plasma insulin levels (median 4 m-units/l, range 1-13 m-units/l versus median 4 m-units/l, range 1-24 m-units/l). After oral glucose the 60 min plasma glucose levels in the women with previous gestational diabetes were significantly higher (8.5 +/- 0.6 versus 6.7 +/- 0.8 mmol/l, P less than 0.05), whereas the plasma insulin level was significantly lower at both 30 min (median 23 m-units/l, range 4-47 m-units/l versus median 55 m-units/l, range 23-100 m-units/l, P less than 0.02) and at 60 min (median 23 m-units/l, range 4-43 m-units/l versus median 60 m-units/l, range 16-126 m-units/l, P less than 0.02). 3. Insulin sensitivity, expressed as the slope of the regression line of plasma glucose level against time after intravenous infusion of insulin (0.05 unit/kg), was similar in the women with previous gestational diabetes and the control subjects (mean slope, -0.17 +/- 0.01 versus -0.17 +/- 0.01). 4. Fasting glucose production rates were similar in the women with previous gestational diabetes and the control subjects (2.2 +/- 0.3 versus 1.9 +/- 0.1 mg min-1 kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Local blood volume changes in women with pelvic congestion measured by applied potential tomography.

1. Applied potential tomography is a new, non-invasive technology for observing changes in blood volume. We have used it to study 12 women with lower abdominal pain caused by pelvic congestion, and 15 control subjects. 2. A significant increase in blood volume of 1.8% was observed in the pelvis of women with congestion when changing from the supine to the erect position, and of 2.7% in the control subjects (P less than 0.0002). The difference between the groups was not significant. 3. The distribution of the area over which blood volume changes took place was significantly different between the two groups (P less than 0.002). More of the posterolateral part of the pelvis was involved in women with pelvic congestion than in the control subjects. 4. Applied potential tomography distinguishes between normal women and those having pelvic congestion with a specificity of 87% and a sensitivity of 75%.

Blood Volume↗
PubMed1991

Abnormalities in fasting circulating proinsulin concentration in mild gestational diabetes.

Fasting plasma proinsulin, insulin and glucose concentrations were measured in ten women with mild gestational diabetes and ten controls matched for race, age (32 +/- 6 vs 31 +/- 6 years), body mass index (28 +/- 8 vs 27 +/- 6) and gestational week (24 +/- 4 vs 25 +/- 4 weeks). There was no significant difference in fasting plasma glucose between these gestational diabetics and their controls (median 4.7, range 3.7-6.0 mmol/l vs 4.5, range 3.4-5.3 mmol/l). The fasting proinsulin levels were significantly higher in the gestational diabetics compared with the controls (median 12.2, range less than 4-14.8 pmol/l vs 5.8, range less than 4-12.8 pmol/l, P less than or equal to 0.02, Wilcoxon Summed Rank Test), while the calculated intact insulin levels (immunoreactive insulin minus proinsulin) were significantly lower (median 14.5, range 6.3-81.8 pmol/l vs 51.6, range 11.7-312 pmol/l, P less than or equal to 0.01). The ratio of proinsulin to calculated intact insulin was significantly higher in the gestational diabetics than the controls (median 0.66, range 0.16-2.04 vs 0.12, range 0.03-0.62), P less than or equal to 0.01). These results demonstrate that gestational diabetics, with normal fasting plasma glucose values, have abnormalities in pancreatic beta-cell secretion, which are likely to be important both in the aetiology of gestational diabetes and non-insulin dependent diabetes.

Adult↗