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Biomedical subjects

G D Carter

Publications and source records attributed to G D Carter.

At least 19 recordsLinked to original sources

Are patients with low serum thyroid stimulating hormone and normal total thyroxine hyperthyroid? Usefulness of 99mTc pertechnetate uptake.

The records of 107 patients who had had thyroid 99m Tc pertechnetate uptake measured, were reviewed. In patients with normal serum thyroxine (T4) and thyroid stimulating hormone (TSH), 35 of 36 with normal uptake and three with high uptake were clinically euthyroid. In patients with high serum T4 and low TSH, seven had normal and 29 had high uptake and all were clinically hyperthyroid. In patients with normal serum T4 and low TSH, 10 of 11 with high uptake were clinically hyperthyroid whereas only two of 18 with normal uptake were. The sensitivity, specificity and positive predictive value of pertechnetate uptake measurements were 83%, 94%, and 91%, respectively. The measurement of pertechnetate uptake is a rapid investigation and may help in the interpretation of patients with undetectable serum TSH found in the presence of normal serum T4.

Adult

Insulin-like growth factor binding proteins in follicular fluid from normal dominant and cohort follicles, polycystic and multicystic ovaries.

There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.

Adult

Follicular fluid concentrations of insulin-like growth factor 1, epidermal growth factor, transforming growth factor-alpha and sex-steroids in volume matched normal and polycystic human follicles.

Thirty-three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF-volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin-like growth factor 1 (IGF1) in the group with PCO, 0.42 (0.13-1.20) U/ml was significantly higher than that of the controls, 0.33 (0.04-0.59) U/ml. All samples tested had less than 1 ng/ml of FF-epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). The patients with PCO syndrome (PCOS) had similar FF-testosterone (T) and FF-progesterone (P) concentrations to volume matched controls, but significantly higher levels of FF-androstenedione (AD) and lower FF-oestradiol (E2). These results suggest that the granulosa cells within the polycystic follicle have a functional defect in their aromatase enzyme complex.

Adult

Oestrogen receptors in colorectal carcinoma.

The oestrogen receptor content of colorectal adenocarcinoma was investigated using an established ligand binding biochemical assay and two more recently introduced techniques using specific monoclonal antibodies (Abbott ER-EIA and ER-ICA assay kits). Twenty nine tumours were investigated by the ligand binding assay. Only one (3.4%) tumour gave a weakly positive result (11 fmol/mg cytosol protein); the rest were all negative. Where sufficient tissue was available, the receptors were also determined by a quantitative immunoassay in 18 patients and an immunohistochemical method in 13 patients. The results were similarly all negative. It is concluded that most colorectal carcinomas, irrespective of sex, are oestrogen receptor negative, and it is thus unlikely that hormonal manipulation would have an influence on the course of the disease.

Adenocarcinoma

The role of chronic anovulation in the polycystic ovary syndrome: normalization of sex-hormone-binding globulin levels after clomiphene-induced ovulation.

A group of anovulatory patients with polycystic ovaries (PCO) was given clomiphene citrate and compared with three control groups: normal women having spontaneous, ovulatory cycles, patients with PCO having spontaneous, regular, ovulatory cycles, and anovulatory patients without PCO. Comparisons were made at precise points of the menstrual cycle (taking the day of ovulation as day 0), using ultrasound estimates of mean follicular diameter, uterine volume, and endometrial thickness, and biochemical measurements of LH, FSH, oestradiol (E2), testosterone (T), progesterone (P) and sex-hormone-binding globulin (SHBG). Before clomiphene treatment, the anovulatory patients with PCO had significantly lower levels of SHBG and higher follicular phase concentrations of LH than all three control groups. After two cycles of clomiphene-induced ovulation, the serum LH concentration fell significantly and levels of SHBG increased significantly to levels similar to those found in spontaneously ovulating women with normal ovaries. It is likely that the loss of the usual considerable rise in E2 in both the follicular and luteal phases of ovulatory cycles is the main reason for the low SHBG found in the PCO syndrome. The loss of the normal P-induced gonadotrophin suppression may be a factor in allowing LH levels to rise.

Adolescent

Is the polycystic ovary a cause of infertility in the ovulatory woman?

Ovulatory women with polycystic ovaries (PCO) were compared with ovulatory women with normal ovaries, using high-resolution ultrasound and biochemical parameters to compare precise points in the menstrual cycle taking the day of ovulation as day 0. The PCO group had higher median follicular phase LH (days 'menses', -5, -3), FSH (days -5, -3) testosterone (days -3, -2) and free androgen index (days -5, -3, -1) than the controls. Women with PCO had a longer follicular phase and larger follicles. These results suggest that abnormal secretion of LH and free testosterone may contribute to the subfertility of women with PCO, possibly by premature activation of the oocyte or by interfering with folliculogenesis.

Adult

The diagnosis of polycystic ovaries in subfertile women.

Laparoscopy was used to identify the polycystic ovary (PCO) in a group of subfertile women. A third were found to have PCO. These patients had higher levels of luteinizing hormone (LH), testosterone (T) and a higher free androgen index (FAI) than those with normal ovaries. Only 15% of patients with laparoscopic evidence of PCO were obese, hirsute and oligomenorrhoeic. Within the PCO group, hirsutism was strongly associated with obesity and a high FAI. A group of subfertile women with PCO and regular cycles was found who had no other identifiable cause for their infertility. These women had higher follicular phase concentrations of LH and higher FAI than ovulatory women with normal ovaries.

Adult

Insulin-like growth factor 1 as an intra-ovarian hormone--an integrated hypothesis and review.

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least 2 samples of clear follicular fluid (FF) collected in the late follicular phase. Dominant follicles contained significantly higher concentrations of insulin-like growth factor-1 (IGF1), oestradiol (E2), progesterone (P) and lower androstenedione (AD) than their matched cohorts. After the luteinizing hormone (LH) surge, a significant increase in dominant FF-IGF1 and FF-P occurred. Log FF-E2 and log FF-P were correlated with both FF-IGF1 and FF volume. Log FF-AD was negatively correlated with FF-volume, FF-E2 and FF-P (but not FF-IGF1). The cohort concentration of FF-IGF1 was correlated with serum IGF1. These results support the hypothesis that IGF1 has a central role in the selection of the dominant follicle.

Adult

The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume.

Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.

Adult

A comparison of follicular fluid levels of insulin-like growth factor-1 in normal dominant and cohort follicles, polycystic and multicystic ovaries.

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least two samples of clear follicular fluid (FF) collected in the late follicular phase. The cohort concentrations of Insulin-like Growth Factor-1 (IGF1) were significantly correlated with serum IGF1 and dominant follicles contained significantly higher concentrations of IGF1 and oestradiol (E2) than their cohorts. After the LH surge, a further significant increase in dominant FF-IGF1 occurred. FF-(log)E2 was significantly correlated with both FF-IGF1 and FF volume. Nine women with the polycystic ovary syndrome (PCOS) and one patient with multicystic ovaries (MCO) associated with weight-loss related amenorrhoea also had follicular aspiration performed. The mean (SD) FF-IGF1 in the PCOS group, 0.42 (0.15) U/ml, was not significantly different from that of the cohorts in the control group, 0.39 (0.13) U/ml. The patient with MCO had both serum and FF-IGF1 concentrations less than 10th centile. These results support the hypothesis that IGF1 has a paracrine (and possibly endocrine) role in the regulation of ovarian function in the human female.

Adult

What are the ultrasound and biochemical features of impending ovulation?

Thirty-two ovulatory women had serial ultrasound measurements of uterine volume, endometrial thickness and leading follicular diameter compared with serum oestradiol, testosterone and sex-hormone binding globulin. Follicular diameter, endometrial thickness and uterine volume were significantly correlated with serum oestradiol. The day before ovulation was characterized by maximal values for oestradiol, testosterone, luteinizing hormone, endometrial thickness, uterine volume and leading follicular diameter. Leading follicular diameter and endometrial thickness in particular, appear to be useful parameters to indicate impending ovulation.

Endometrium

Elevated free androgen index as an indicator of polycystic ovaries in oligomenorrhoea without obesity or hirsuties.

A group of oligomenorrhoeic women without obesity or hirsuties was investigated with high-resolution ultrasound, laparoscopy and biochemical parameters. In this series, polycystic ovaries (PCO), as defined by ultrasound and laparoscopy, are a common cause of oligomenorrhoea in women without the classic symptoms, and were strongly associated with an elevated free androgen index (FAI). Despite an elevated FAI, these women were not hirsute, It would seem reasonable to include a FAI in the investigation of the oligomenorrhoeic woman, along with the more 'standard' tests, such as thyroid function and a prolactin level.

Adult

Factors influencing the free androgen index in a group of subfertile women with normal ovaries.

Eighty-five regularly cycling women with normal ovaries at laparoscopy, were studied to determine the factors that influence the free androgen index (FAI). It was found that body mass index (BMI), age of the patient and the phase of the menstrual cycle that the blood was collected can all affect the FAI. It is recommended that where possible, specimens should be collected in the early follicular phase to avoid misinterpretation of the result.

Age Factors

Oestradiol assays: applications and guidelines for the provision of a clinical biochemistry service.

This paper reports on the provision of a clinical biochemistry service for serum oestradiol. The pathophysiology and recognised applications of oestradiol assays are discussed and the current availability of assay reagents and methodologies reviewed. Data are presented on the analytical performance of assays for serum oestradiol in the UK External Quality Assessment Scheme (UKEQAS) and general guidance is offered to laboratories providing a diagnostic service for this analyte.

Adult

Hereditary angioedema and thyroid autoimmunity.

Sera from 91 patients with hereditary angioedema were screened for thyroid antibodies. The results for the 77 patients more than 17 years old were compared with previously published data for the prevalence of thyroid disease in a large community (Whickham). Of the female patients with hereditary angioedema, the prevalence of thyroglobulin antibodies (TGA) was 14.0%, higher than the expected 3% (p less than 0.001). The prevalence of thyroid microsomal antibodies (TMA) was 20%, also higher than the expected 7.6% (p less than 0.01). The age distributions of the females in both groups differed: in the group with hereditary angioedema there was a greater proportion of younger patients which should have resulted in a lower prevalence of thyroid antibodies. Adjusting for related patients with hereditary angioedema, there was still an increased prevalence of TGA (p less than 0.01) and TMA (p less than 0.01).

Adolescent

Oral spironolactone: an effective treatment for acne vulgaris in women.

The effect of oral spironolactone (200 mg daily) on acne vulgaris has been studied in 21 women in a randomized, placebo-controlled, double-blind crossover study using 3 month treatment periods. Compared with placebo, spironolactone produced significant improvement as assessed by subjective benefit (P less than 0. 001), number of inflamed lesions (P less than 0 . 001) and by an independently evaluated photographic method (P less than 0 .02). There was a fall in sex hormone binding globulin but no significant changes in plasma testosterone and derived free testosterone. Initial plasma androgen levels were no higher in responders than in non-responders, nor did oral contraceptive use appear to affect clinical response. Spironolactone is a useful alternative therapy for women with acne vulgaris.

Acne Vulgaris