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Biomedical subjects

H N Cohen

Publications and source records attributed to H N Cohen.

At least 19 recordsLinked to original sources
PubMed1990

An evaluation of human chorionic gonadotrophin (HCG) therapy in boys with delayed puberty.

Fifty male patients with delayed pubertal development (chronological age 13.3-17.6 years; bone age 9.5-14 years) were treated with human chorionic gonadotrophin (HCG) 1500-2000 units twice weekly for six months to promote pubertal development and accelerate growth. Response was compared with an untreated control group of 28 patients (chronological age 12.5-17.5 years; bone age 7.0-13.0 years). Forty-four of 46 patients in the treatment group achieved genital stage 3 or 4 by the end of therapy; untreated patients either remained unchanged or advanced only one genital stage during this period. Testicular volumes increased from a median 4.5 ml (range 1-12 ml) to 9 ml (range 3.5-15 ml) in the treated patients. In untreated patients testicular volume increased from 6.0 ml (range 2-10 ml) to 9.5 ml (range 4-20 ml) over the same period. In patients initially growing at less than 7.0 cm/year height velocity increased from 3.9 cm/year (range 0-6.6 cm/year) to 12.7 cm/year (range 8.9-16.8 cm/year) during therapy, falling to 6.0 cm/year (range 0-12 cm/year) in the three-month period immediately following treatment. Patients initially growing at greater than 7.0 cm/year showed variable responses to treatment. Prepubertal patients showed the greatest acceleration in annual growth compared with controls. Treated patients with an initial skeletal age less than 12.0 years showed either a final height (when known) which was less than initially predicted or a significant reduction in predicted height following treatment. Skeletal age greater than 12.0 years was not associated with excess osseous maturation. In conclusion, pre-pubertal children growing at less than 7 cm/year show the greatest benefit from HCG therapy, but final height may be prejudiced if initial bone age is less than 12 years.

Adolescent↗
PubMed1988

Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration.

Twenty-two boys (9 with delayed puberty and 13 with short stature) ages 12.3 - 17.8 yr, and 10 adult males with idiopathic hypogonadotropic hypogonadism (ages 17.3 - 41.1 yr) have been studied following pulsatile, sc GnRH therapy (240 ng/kg/pulse) over 6 days. Mean pre- and post-therapy LH and FSH concentrations were estimated by 15 min blood sampling over 3-h periods immediately before and at the end of the treatment period. There were significant correlations between the mean pre- and posttreatment LH and FSH concentrations (r = 0.82, p less than 0.001 and r = 0.51, p less than 0.02, respectively) for the 2 groups of peripubertal boys when assessed together. Nine of the 10 adults with hypogonadism showed proportionately greater gonadotropin increments following pulsatile therapy when compared with the peripubertal boys. Standard bolus GnRH tests (100 micrograms iv) did not differentiate between the three groups of patients before pulsatile GnRH therapy. Bolus GnRH tests could predict the subsequent response to pulsatile therapy in the peripubertal boys only. There was no significant change in LH increments following the GnRH bolus tests in either group, after pulsatile GnRH administration (p greater than 0.1). Early response to pulsatile GnRH administration is dependent upon the maturity of the hypothalamic-pituitary-testicular axis in males with delayed puberty or short stature. Patients with hypogonadotropic hypogonadism do not show this relationship.

Adolescent↗
PubMed1986

Impaired thyrotrophin secretion following the administration of thyrotrophin-releasing hormone in type II diabetes mellitus.

Serum thyrotrophin has been measured before and after the intravenous administration of 200 micrograms of thyrotrophin-releasing hormone in 91 white subjects (33 stable diabetic patients and 58 healthy controls), none of whom had any clinical evidence of thyroid or pituitary dysfunction. Seven of the diabetic subjects failed to achieve a rise of serum thyrotrophin of greater than 2 mU/l above basal concentrations, as compared with only one of the control subjects (P = 0.006). The difference in response between diabetics and controls was confined to patients with Type II (non-insulin-dependent) diabetes: thus 5 of 13 Type II patients and 2 of 20 Type I (insulin-dependent) patients failed to show a normal response to thyrotrophin releasing hormone injection. No significant effect of glycaemic control on thyrotrophin responses was noted. These results suggest that Type II diabetes mellitus may be a cause of impaired thyrotrophin secretion in patients with no clinical evidence of pituitary disease. The mechanism for this impaired pituitary hormone release remains to be clarified.

Adolescent↗
PubMed1985

Effect of sulphonylurea administration on insulin secretion and amino acid metabolism in non-insulin-dependent diabetic patients.

Sulphonylureas lower blood glucose but other metabolic effects have been little studied. In an assessment of carbohydrate and amino acid metabolism in 9 patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after 3 months' therapy with gliclazide, glycaemic control was improved (mean +/- S.D. glycosylated haemoglobin 13.8 +/- 1.9% before therapy, 10.2 +/- 2.1% after therapy (p less than 0.01], but fasting amino acid levels were not altered. In contrast, postprandial levels of branched chain amino acids (BCAA) were significantly reduced: total BCAA (valine, leucine, and isoleucine) 120 mins following a standard test meal fell from 717 +/- 71 mumol/l before therapy to 600 +/- 90 mumol/l after 3 months' therapy (p less than 0.01). This finding implies an increased action of endogenous insulin on skeletal muscle to promote uptake of BCAA postprandially and, in accord with this, peripheral insulin levels were significantly increased following drug treatment (peak insulin level 55.6 +/- 20.2 mU/l before therapy, 91.3 +/- 17.9 mU/l after therapy (p less than 0.01]. Sulphonylurea drugs therefore do not simply have a hypoglycaemic action but also affect amino acid metabolism in NIDDM patients.

Adult↗
PubMed1985

Comparison of oral glucose loading and intravenous glucagon injection as stimuli to C-peptide secretion in normal men.

In 10 healthy men, we have compared the respective effects of an intravenous injection of glucagon (1 mg) and an oral glucose load (75 G) in eliciting the release of C-peptide and insulin from the pancreas. Serum C-peptide and insulin concentrations increased respectively to median values of 190% and 500% at 6 minutes after glucagon injection, and 344% and 794% at 30 minutes and 268% and 278% at 60 minutes following glucose ingestion. The oral glucose load was as effective as glucagon injection in testing beta cell function and was free from the unpleasant side effects (nausea, vomiting, syncope) commonly associated with glucagon. We conclude that oral glucose loading is probably the test of choice to elicit C-peptide release when screening populations of normal subjects for adequacy of beta cell function.

Adult↗
PubMed1985

Prolactin dynamics and tumour size in the prediction of surgical outcome for prolactinoma.

Each of 62 females were studied for a period of between two and 72 months (mean 36 months) following the removal of a prolactinoma by transsphenoidal pituitary surgery. Our aims were to define the relationships between pre- and post-operative features, the operative findings and the functional outcome. Pre-operative serum prolactin (PRL) concentrations correlated with tumour diameter (r = 0.55, p less than 0.001). Following surgery two groups of patients were identified: Group 1, 46 spontaneously and regularly menstruating patients and Group 2, 16 patients with persistent amenorrhoea. The patients in Group 1 had significantly lower pre-operative and post-operative serum (PRL) concentrations (p less than 0.02 and p less than 0.001 respectively) and significantly greater PRL responses to thyrotrophin releasing hormone (TRH) and metoclopramide stimulation after surgery (p less than 0.001). There was not a significant difference in tumour size between the groups. Forty-four (96 per cent) of the patients in Group 1 had normal post-operative serum PRL concentrations within one week of surgery. By comparison (p less than 0.001) only 42 and 20 per cent respectively of Group 1 patients who were tested had normal TRH and metoclopramide evoked PRL secretion following surgery. Return of regular menstruation was associated with cessation of galactorrhoea in 44 patients (96 per cent) and ovulation occurred in 37 of 38 menstruating patients for whom data are available. All patients with normal TRH and metoclopramide stimulation tests menstruated spontaneously. Nevertheless most patients who menstruated did so in spite of retaining suppressed PRL responses. Of 46 patients followed to date whose serum PRL was normal one week after surgery, seven later were found to have an elevation of serum PRL outside the normal range but in only two has this been persistent. We suggest that a single measurement of serum PRL one week following transsphenoidal pituitary surgery for prolactinoma provides a good basis for deciding about the future management of patients who desire menstruation and pregnancy.

Female↗
PubMed1984

Dissociation of adrenarche and gonadarche in diabetes mellitus.

Serum concentrations of testosterone and dehydroepiandrosterone sulphate (DHAS) have been measured in 10 stable insulin-dependent diabetic (IDD) males (chronological age (CA) range 13.0-17.5 years). Their results have been compared with those of a control population of 69 non-diabetic males who presented with mild constitutional growth delay and whose skeletal maturity and pubertal development were similar to the diabetic subjects. Within bone ages (BA) 11.0-14.5 years no significant difference was observed between the serum testosterone concentrations of the diabetic patients and controls: diabetic males, 8.2 (0.3-25) nmol/l (median and range); controls, 7.0 (less than 0.3-23) nmol/l. In contrast, within BA 11.0-14.5 years, the diabetic males had significantly lower serum DHAS concentrations: diabetic males, 1.1 (0.7-4.2) mumol/l; controls, 3.7 (0.7-5.6) mumol/l (P less than 0.001). The serum DHAS concentrations of the diabetic males were also significantly lower than the controls when matched separately for pubic hair and genital development, testicular volume and serum testosterone, (in each comparison P less than 0.02). Serum DHAS concentrations of the diabetic males did not correlate significantly with CA, BA, BA delay (CA-BA), age of onset of diabetes, duration of diabetes, or glycosylated haemoglobin (GHb), but significant correlation was observed between BA delay and duration of diabetes, r = 0.65, P less than 0.05. We conclude that gonadarche appears to proceed despite delayed adrenarche in IDD males. This study presents further evidence in favour of adrenarche and gonadarche being independent physiological events. The causes and clinical significance of low serum DHAS concentrations in adolescent diabetic males remain to be established.

Adolescent↗
PubMed1984

Contrasting effects of subcutaneous pulsatile GnRH therapy in congenital adrenal hypoplasia and Kallmann's syndrome.

A patient with congenital adrenal hypoplasia (AH) and hypogonadotrophic hypogonadism was treated with pulsatile subcutaneous GnRH therapy for 16 weeks in an attempt to induce puberty. No rise in serum LH or FSH concentrations occurred despite increasing doses of GnRH (2.8 micrograms/pulse-22.4 micrograms/pulse). In contrast a similar programme of therapy successfully initiated the biochemical changes of puberty in a patient with Kallmann's syndrome. Both patients before therapy had low basal serum LH and FSH concentrations with blunted LH and FSH responses to GnRH stimulation. After 1 week, serum LH and FSH rose into the normal adult range in the patient with Kallmann's syndrome. This study fails to confirm a previous report which suggested that intermittent low dose GnRH therapy may be of value in inducing puberty in AH. The reasons for the difference of pituitary responsiveness to GnRH in AH and Kallmann's syndrome are unclear at present.

Adrenal Glands↗
PubMed1984

Effects of diabetic control and biosynthetic human insulin on blood rheology in established diabetics.

Blood rheology (blood viscosity, haematocrit, plasma viscosity, erythrocyte sedimentation and deformability) was measured in 22 diabetics in a study to compare animal insulins with biosynthetic human insulin. All rheological variables were significantly abnormal in the diabetics when compared with matched normal controls, and were not influenced by the type of insulin injected. However, blood rheology was related to diabetic control, as judged by glycosylated haemoglobin levels; when diabetic control was worst (mean glycosylated haemoglobin 11%), blood viscosity was significantly higher and red cell deformability significantly lower than when control was at its best (mean glycosylated haemoglobin 9.5%). A similar correlation between mean red cell deformability and mean glycosylated haemoglobin was found when individual diabetics were compared (r = 0.66; p less than 0.001). The occurrence of abnormal blood viscosity and red cell deformability during periods of poor diabetic control may contribute to the development of diabetic vascular complications.

Adolescent↗
PubMed1984

Serum growth hormone (GH) and the responses to thyrotropin-releasing hormone (TRH) in diabetes mellitus: lack of evidence for TRH evoked GH secretion.

Since TRH has been reported to evoke GH secretion in diabetic patients, we have investigated the influences of the enhanced GH secretion normally seen in diabetic patients on this response by measuring serum GH concentrations in 27 non-ketotic, stable, insulin-dependent diabetic (IDD) patients (14 male, 13 female). GH concentrations were measured over periods of 1 hr prior to and 1 hr following IV administration of both 200 micrograms TRH and 2 ml N Saline given on separate days. GH concentrations were not statistically significantly different between males and females during the two 120 min test periods and in individual patients GH concentrations did not differ significantly at any time during the tests. Sixteen of the 27 patients (Group 1) demonstrated elevation of serum GH following TRH, which was not statistically different from 11 of 27 patients who showed increased GH concentrations following saline administration. Seven subjects (4 male, 3 female) had a higher peak GH concentration following TRH than during their own 2 pre-injection test periods or following saline. Eleven patients failed to show any GH rise following IV TRH (Group 2). During the TRH test periods integrated GH concentrations in Group 1 patients were not statistically significantly different from those of Group 2: Group 1, 7.1 (0.7-15.8) (median and range) mU.min.l(-1), Group 2, 2.7 (0.4-25.4) mU.min.l(-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗
PubMed1983

Serum luteinizing hormone and follicle-stimulating hormone and the response to luteinizing hormone-releasing factor in children and adolescents with isolated growth hormone deficiency.

Serum concentrations of LH and FSH were measured in 95 patients (62 males and 33 females) with presumed isolated GH deficiency [chronological age range, 5-17 yr; bone age (BA) range, 2-15.5 yr] before and after the iv administration of 100 micrograms LRF. The results were compared to those of patients of similar skeletal maturity, derived from a population of 136 children (79 males and 57 females) with constitutional short stature. Mean serum LH concentrations were similar in the GH-deficient and control patients of either sex within the age ranges studied. Mean basal FSH concentrations in males with GH deficiency were similar to the controls between BA 2 to less than 10 yr and more than 12 to 15.5 yr. The mean peak, peak minus basal, and integrated responses of LH concentrations after the iv administration of LRF were not significantly different in patients with GH deficiency from the responses in normal short children of similar ages. After LRF administration, GH-deficient males of BA between 2 and less than 10 yr had diminished FSH responses. The mean peak concentration was 1.9 +/- 0.2 ng/ml in GH-deficient males (n = 34) and 2.8 +/- 0.3 ng/ml (less than 0.05) in control males (n = 45). GH-deficient males of BA between 10-12 yr had slightly elevated mean peak and total integrated FSH concentrations; in GH-deficient patients (n = 15), these values were 2.7 +/- 0.2 ng/ml and 2.1 +/- 0.2 ng X min ml-1, respectively; and in controls (n = 18), they were 1.8 +/- 0.2 ng/ml (P less than 0.05) and 1.5 +/- 0.2 ng X min ml-1 (P less than 0.05). In the BA range from 4-8 yr, the mean peak response to LRF was diminished in GH-deficient females (n = 24; 4.0 +/- 0.4 ng/ml) compared to that in control females (n = 18; 6.0 +/- 0.9 ng/ml; P less than 0.05). In the BA range from more than 8 to 13 yr, the corresponding mean peak FSH concentration in GH-deficient females (n = 9) was 3.2 +/- 0.3 ng/ml; in control females (n = 39), it was 4.9 +/- 0.4 ng/ml (P less than 0.05). This study fails to confirm previous reports that LRF-evoked LH release is diminished in patients with isolated GH deficiency compared to that in normal short children of similar skeletal maturity. Small differences in group mean FSH concentrations were noted, but these findings are of limited clinical importance because an extensive degree of overlap of individual FSH concentrations was found in all comparisons between GH-deficient patients and normal children.

Adolescent↗
PubMed1982

Effects of growth hormone, glucose and insulin on the factor VIII complex.

The relationship of growth hormone (GH) to the factor VIII complex (VIIIC, VIIIRAg and VIIIRRCo) was investigated. No correlation between basal levels of GH and factor VIII assays was found in 23 subjects. No significant change in factor VIII assays was observed after GH suppression by oral glucose or bromocriptine. After insulin-induced hypoglycaemic all three factor VIII assays rose and fell in parallel with GH. However, after exercise the rise in VIIIC and VIIIRAg preceded the rise in GH; and no changes in factor VIII assays were observed after administration of thyrotrophin releasing hormone (TRH) (releasing endogenous GH) or exogenous GH. These findings do not support a role for GH in the regulation of plasma levels of VIIIC, VIIIRAg or VIIIRRCo.

Antigens↗
PubMed1981

Clinical value of adrenal androgen measurement in the diagnosis of delayed puberty.

Serum levels of the adrenal androgens dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), and androstenedione (A) were measured in 90 males (age range 14 1/2--26 years) presenting with delayed puberty to an adult endocrine clinic over a period of 3 years. The results show that adrenal androgen levels are significantly lower (p less than 0.0005) in subjects with growth-hormone (GH) deficiency than in patients with simple and constitutional delayed puberty and other, less common, conditions. By contrast, subjects with hypogonadotropic hypogonadism had significantly raised values (p less than 0.0005). On initial presentation DHA and DHAS measurements correctly identified all GH-deficient subjects and in addition DHAS measurements identified 89% of subjects with hypogonadotropic hypogonadism. It is suggested that measurement of serum levels of DHA and DHAS may assist greatly in the early diagnosis of conditions causing delayed puberty, and thus may prevent unnecessary delay in treatment.

Adolescent↗