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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 145 records · Page 8Linked to original sources
PubMed1990

A rat granulosa cell plasminogen activator bioassay for FSH in human serum.

A previously described in-vitro rat granulosa cell plasminogen activator bioassay for FSH has been modified and applied in the assay of human serum. This modified method consists of exposing the diethylstilboestrol-stimulated granulosa cells from 25- to 26-day-old rats to FSH or test substance for 3.5 h in wells coated with 125I-labelled fibrinogen and treated with thrombin. Following stimulation with FSH, the dose-related production of plasminogen activator was measured as the degree of 125I-labelled fibrinolysis in the presence of added plasminogen. Using the urinary FSH/LH bioassay reference preparation as the assay standard, the useful range of the assay was 0.3-15 IU/l, with an assay sensitivity of 0.3 IU/l. As determined using purified glycoprotein hormone preparations, the assay was highly specific for FSH. The minor degree of FSH bioactivity measured in some of the hormone preparations was accounted for by the amount of FSH contamination in these preparations. To abolish interference caused by unknown serum factors, we heat-treated the serum samples for 15 min at 56 degrees C before the assay. The results indicated that neither immunoreactivity nor bioactivity was affected by this treatment. Furthermore, heat-treated human sera gave responses parallel to the standard curve at the three dose levels (2, 4 and 8 microliters) studied. We used this bioassay to estimate the FSH-like bioactivity in 15 human serum samples. The estimates of immunoreactive FSH in these samples correlated well with the corresponding FSH bioactivity (r = 0.745, n = 15 and P less than 0.05). The results indicate that with this sensitive and rapid (completed within 24 h) bioassay, it should be possible to measure FSH bioactivity in heat-treated human serum samples.

Animals↗
PubMed1989

One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE: To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN: Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING: Infertility clinic. PATIENTS: 118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS: Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT: Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS: Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.

Abortion, Spontaneous↗
PubMed1989

The use of a short regimen of buserelin, a gonadotrophin-releasing hormone agonist, and human menopausal gonadotrophin in assisted conception cycles.

The outcome of in-vitro fertilization treatment using buserelin, an agonist of luteinizing hormone releasing hormone, given in a short stimulation regimen with human menopausal gonadotrophin (HMG), was compared with a conventional regimen including clomiphene citrate (CC). A total of 94 infertile women underwent cycles of treatment with intranasal buserelin, 500 micrograms daily from the first day of menstruation and also HMG daily from the third day. The same patients had previously undergone unsuccessful treatment cycles with CC and HMG. Overall, addition of buserelin resulted in fewer cycles being abandoned (10 versus 34%) and none of the patients ovulated prior to collection. The mean total dose of HMG required was increased by 74% in buserelin cycles. Significantly more oocytes were collected with buserelin treatment (mean 5.9 versus 4.4, P less than 0.01) and, thus, significantly more embryos were transferred (mean 2.3 versus 1.2, P less than 0.0001) although fertilization and cleavage rates were unchanged. Fifteen pregnancies were achieved, giving a clinical pregnancy rate of 22% per embryo transfer. These pregnancies resulted in 16 live births (7 singletons, 3 twins, 1 triplets). Four pregnancies failed before 14 weeks gestation. We conclude, therefore, that the substitution of buserelin for CC for ovarian stimulation in poor responders results in an improved outcome, both in terms of the number of oocytes collected and the pregnancy rate per treatment cycle.

Administration, Intranasal↗
PubMed1989

Most women with acne have polycystic ovaries.

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty-eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities.

Acne Vulgaris↗
PubMed1989

Steroid responses to ACTH in women with polycystic ovaries.

Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

17-alpha-Hydroxypregnenolone↗
PubMed1989

Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients.

This paper reports an analysis of the clinical, endocrine and ultrasound data within a population of 556 patients with ultrasound-diagnosed polycystic ovaries. Compared with those not so affected, hirsutism was associated with a higher mean serum testosterone concentration, infertility was associated with higher mean gonadotrophin concentrations, obesity was associated with a higher mean serum testosterone concentration, hyperprolactinaemia was associated with a lower mean serum testosterone concentration and smaller ovaries, alopecia was associated with lower mean serum LH and testosterone concentrations, and acanthosis nigricans was associated with obesity and a raised mean serum testosterone concentration. The heterogeneity illustrates the limitations in the use of specific clinical or endocrine criteria as requirements for the diagnosis of the polycystic ovary syndrome.

Acanthosis Nigricans↗
PubMed1989

Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle.

Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment. Hypertension was present in nine (26%) but only three (9%) had electrocardiographic left ventricular hypertrophy. Echocardiography showed ventricular hypertrophy in 12 (48%) and increased left ventricular mass in 17 (68%) patients. Holter monitoring detected important ventricular arrhythmias in 14 patients. Thallium-201 scanning showed evidence for coronary heart disease in eight patients. Systolic time intervals were normal except when there was coexistent ischaemic heart disease. A comparison between 19 acromegalic patients with no other detectable cause of heart disease and 22 age matched controls showed appreciably abnormal left ventricular diastolic function in the group with acromegaly. The abnormalities shown did not correlate with left ventricular mass or wall thickness. There was no difference in diastolic function between patients with active acromegaly and those with treated acromegaly. Hypertensive acromegalic patients had worse diastolic function than hypertensive controls, suggesting that hypertension may further impair the left ventricular diastolic abnormality in acromegaly. This is the first study to find evidence of subclinical cardiac diastolic dysfunction in acromegaly and it supports the suggestion that there is a specific disease of heart muscle in acromegaly.

Acromegaly↗
PubMed1988

Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome?

A potential association between abnormal electromyographic activity--that is, decelerating bursts and complex repetitive discharges--of the urethral sphincter and difficulty in voiding was examined in 57 women with urinary retention. Abnormal electromyographic activity was found in 33. Ultrasonography of the ovaries in 22 of the 33 women showed that 14 had polycystic ovaries. Of the other eight women, two had had oophorectomies, one had shrunken ovaries and ovarian failure, and one had previously undergone oophorectomy and the other ovary could not be seen; in one neither ovary could be seen, and three had ovaries of normal appearance, although two of these women were taking the contraceptive pill. Thirteen of the group had endocrine symptoms and signs characteristic of the polycystic ovary syndrome. Videocystometrography in 17 of the women who were examined by ultrasonography showed low flow rates and high residual volumes of urine after micturition in 12 women who could void, the other five having chronic urinary retention. A speculative hypothesis for the observed association of impaired voiding, abnormal electromyographic activity of the urinary sphincter, and polycystic ovaries is advanced, based on the relative progesterone deficiency that characterises the polycystic ovary syndrome. Progesterone stabilises membranes, and its depletion might permit ephaptic transmission of impulses between muscle fibres in the muscle of the urethral sphincter, giving rise to the abnormal electromyographic activity. This may impair relaxation of the sphincter, resulting in low flow rates of urine, incomplete emptying of the bladder, and, finally, urinary retention.

Adult↗
PubMed1988

Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome.

Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.

Abortion, Spontaneous↗
PubMed1988

Outcome of pregnancy in underweight women after spontaneous and induced ovulation.

Low maternal weight before pregnancy and poor weight gain during pregnancy are known to result in an increased prevalence of low birthweight infants. Low body weight is also an important cause of amenorrhoea. The hypothesis that amenorrhoeic underweight women who become pregnant after induction of ovulation are more at risk of delivering low birthweight infants than underweight women who ovulate spontaneously was investigated. Forty one pregnant women in whom ovulation had been induced and 1212 in whom ovulation was spontaneous were studied. Women ovulating spontaneously whose weight was normal and who showed good weight gain during pregnancy (greater than 450 g a week) had the lowest incidence (6%) of babies who were small for gestational age. Underweight women (body mass index less than 19.1) who ovulated spontaneously had a threefold increased risk of delivering babies who were small for gestational age (18%). Overall, the women in whom ovulation had been induced had an even higher risk of babies who were small for dates (25%), and the risk was greatest (54%) in those who were underweight. The outcome of pregnancy is related to weight before conception, which in many cases reflects nutritional state; lack of spontaneous ovulation indicates an increased risk of producing a small for dates infant. The most suitable treatment for infertility secondary to weight related amenorrhoea is therefore dietary rather than induction of ovulation.

Body Weight↗
PubMed1988

Uterine growth in the follicular phase of spontaneous ovulatory cycles and during luteinizing hormone-releasing hormone-induced cycles in women with normal or polycystic ovaries.

The uterine response to follicular growth in luteinizing hormone-releasing hormone (LH-RH)-induced ovulatory cycles was assessed by serial ultrasound measurement of uterine cross-sectional area and endometrial thickness in 23 cycles in women with normal ovaries and 24 cycles in women with polycystic ovaries. Nine women with spontaneous ovulatory cycles also were studied. The authors correlated uterine cross-sectional area and endometrial thickness with follicle diameter (FD) and serum estradiol-17 (E2). In women with either normal or polycystic ovaries, there was an E2-related increase in uterine cross-sectional area and endometrial thickness, but both uterine area and endometrial thickness were greater in the late follicular phase of women with polycystic ovaries compared with those with normal ovaries.

Endometrium↗
PubMed1988

Pulsatile luteinizing hormone-releasing hormone therapy in women with polycystic ovary syndrome.

Induction of ovulation with pulsatile luteinizing hormone-releasing hormone (LH-RH) therapy was attempted in 48 women with polycystic ovary disease (PCOD) and clomiphene citrate (CC) resistant anovulation. Fourteen women ovulated regularly, 23 ovulated variably, but 11 did not ovulate at all. Fifty-two of the 108 cycles of pulsatile LH-RH therapy alone (15 mu gm per pulse, one pulse every 90 minutes) administered through the subcutaneous route were ovulatory. In patients who did not ovulate on subcutaneous LH-RH, treatment with CC (100 mg per day for 5 days) was added to the LH-RH therapy in an additional 33 cycles, of which 21 were ovulatory. In those who did not respond to the combination of treatments, the same dose of LH-RH was administered intravenously: 14 of 29 cycles of intravenous therapy were ovulatory. The overall cumulative conception rate after 6 months of therapy was 60%. When recalculated for ovulatory cycles alone it was 90%, indicating that failure of ovulation was the only cause of the failure of conception. Analysis of the clinical and endocrine findings indicated that failure to ovulate was associated with obesity and hyperandrogenization. Ten of the 23 conceptions ended in miscarriage, 8 within 4 weeks of ovulation. The authors conclude that infertility in patients with PCOD is not optimally corrected by pulsatile LH-RH therapy.

Body Weight↗
PubMed1988

Growth hormone facilitates ovulation induction by gonadotrophins.

The addition of biosynthetic human growth hormone (GH) to treatment with human menopausal gonadotrophin (hMG) significantly augmented the ovarian response in four patients treated for in-vivo and three patients treated for in-vitro fertilization who had previously been resistant to hMG. The amount, duration of treatment and daily effective dose of hMG were all reduced by growth hormone. This action of growth hormone offers a new approach to ovulation induction.

Adult↗
PubMed1988

Familial polycystic ovaries: a genetic disease?

High resolution ultrasonography was used to establish the presence of polycystic ovaries (PCO) in 50 women with symptoms of polycystic ovary syndrome and in 17 women with congenital adrenal hyperplasia. One hundred and thirty-seven post-menarcheal, premenopausal female members of the families of these patients were scanned to assess the heredity of the condition. Familial PCO was found in 56 of the 61 pedigrees (92%) in which sufficient members were available for study. The frequency of PCO in the relatives of the patients with congenital adrenal hyperplasia was no different from that found in the main group. Twenty-four out of thirty-six (67%) mothers of probands and 45 out of 52 (87%) sisters of probands were affected. The segregation ratio (fraction of females affected) for all sibships was 107 out of 133 (80.5%). The volumes of the polycystic ovaries (mean 9.97 ml, 95% confidence limits (CL) +/- 0.75) were significantly different from those of the normal ovaries (mean 5.38 ml, 95% CL +/- 0.26) (P less than 0.0001), although there was no significant difference between the volumes of the ovaries of the probands and those of their affected relatives. Even after allowing for a high frequency of PCO in the general population (22%), the observed segregation ratios were significantly different from those predicted for autosomal dominant (P less than 10(-4)) and X-linked dominant (P = 0.0002) modes of inheritance. A number of mechanisms which might account for the observed segregation ratio are considered. These include meiotic drive due to a genetic segregation distorted, vertical transmission of an infective agent, and environmental factors, such as the effect of maternal androgen on gonadal development.

Female↗