bluuebunny/crossref_metadata_2025_split huggingface dataset:
HISTIDYL‐PROLINE DIKETOPIPERAZINE SUPPRESSES PROLACTIN SECRETION IN HUMAN PITUITARY TUMOUR CELL CULTURES
Authors: MELMED S. , CARLSON H. E. , HERSHMAN J. M. 
Published: March 2008

SUMMARYBecause histidyl‐proline diketopiperazine (HPD), a metabolite of TRH, has been shown to suppress prolactin (PRL) release by rat pituitary tumour cells, human pituitary tumour cells were exposed to this compound. Monolayer cell cultures were initiated from pituitary tissue removed by transsphenoidal surgery from two patients with prolactin‐secreting microadenomas. Tumour fragments were mechanically dispersed; cells were seeded into multiwell plates and incubated in Ham's F‐10 medium enriched with fetal calf serum (20%). HPD (7±5 ng/ml) suppressed PRL release by both tumour cell cultures. Theophylline reversed the inhibition of PRL release induced by HPD. The data raise the possibility that HPD may act as an endogenous prolactin‐inhibiting factor in man.
AN IMPROVED METHOD FOR THE RADIOIMMUNOASSAY OF FREE‐THYROXINE IN SERUM DIALYSATES
Authors: GILES A. F 
Published: March 2008

SUMMARYA convenient, sensitive radioimmunoassay of free thyroxine in serum dialysates is described. The method utilizes a solid phase separation system (pre‐formed double antibody) and a relatively short incubation period (220 min) with a staggered addition of tracer. Blanks were low and consistent. The normal range for non‐pregnant euthyroid samples (n= 59) was 11–23 pmol/1. Third trimester pregnancy samples were mostly within the normal range but at the lower end. Patients on T4 replacement showed a much wider variation in free T4 levels with many samples in the hyperthyroid region. Some hypothyroid samples had undetectable free T4 levels and hyperthyroid samples were frequently greater than 80 pmol/l.
NOCTURNAL NATRIURESIS IN HYPERTHYROIDISM
Authors: BELL G. M. , SAWERS J. S. A. , TOFT A. D. , DOIG A. 
Published: March 2008

SUMMARYWe measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P < 0·05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24‐h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P < 0·005) and urinary flow (P < 0·05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0·73, P < 0·01). Twenty‐four hour urinary calcium output was significantly greater (P < 0·02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.
THYROID HORMONES AND THE REGULATION OF THYROID FUNCTION IN MEN WITH COELIAC DISEASE
Authors: FARTHING M. J. G. , REES LESLEY H. , EDWARDS C. R. W. , BYFIELD P. G. H. , HIMSWORTH R. L. , DAWSON A. M. 
Published: March 2008

SUMMARYA specific pattern of thyroid hormone abnormalities was observed in twenty‐seven men with coeliac disease which differed from that observed in patients with non‐thyroidal illness (NTI). Serum free thyroxine (FT4) was reduced, but increased after gluten was withdrawn from the diet and jejunal morphology improved. Total T4 (TT4), total triodothyronine (TT3), free triiodothyronine (FT3) and reverse T3 (rT3) levels were unchanged, unlike the findings in nineteen men with Crohn's disease when TT3 fell, rT3 tended to rise but TT4, FT4 and FT3 levels were normal, except FT4 was significantly higher in a subgroup of patients who were more severely ill. The thyroid hormone changes in Crohn's disease are those expected in NTI. Basal serum thyrotrophin (TSH) was normal in all but one of the patients with coeliac disease but 45% of untreated coeliacs had exaggerated responses of TSH to thyrotrophin releasing hormone, an observation which cannot be explained as a feature of NTI. These changes in thyroid hormones in coeliac disease could not be attributed to abnormalities of thyroxine‐binding globulin or thyroxine‐binding prealbumin, and thyroid autoantibodies were not detected in these patients. Hence, different patterns of thyroid hormone abnormalities can occur in different diseases of the same organ in patients of equivalent nutritional status. Circulating gluten peptides may be involved in the hypothalamic‐pituitary disturbance of coeliac disease.
PROPRANOLOL VERSUS CARBIMAZOLE AS THE SOLE TREATMENT FOR THYROTOXICOSIS. A CONSIDERATION OF CIRCULATING THYROID HORMONE LEVELS AND TISSUE THYROID FUNCTION
Authors: O'MALLEY B. P. , ABBOTT R. J. , BARNETT D. B. , NORTHOVER B. J. , ROSENTHAL F. D. 
Published: March 2008

SUMMARYSerum triiodothyronine (T3), thyroxine (T4) and reverse triiodothyronine (rT3) levels were measured in seven hyperthyroid patients during 2 months of propranolol therapy and subsequently during 2 months of carbimazole. In keeping with previous observations, there was a slight fall in serum T3 level accompanied by elevations of serum T4 and rT3 during propranolol. As a consequence of carbimazole treatment, serum T3 and T4 fell markedly and rT3 was undetectable.Three parameters of tissue thyroid function, glucagon stimulated cyclic AMP levels, systolic time intervals (STI) and visual evoked response (VER) were monitored in parallel to the peripheral hormone changes. There was no real improvement in tissue function during propranolol treatment. During carbimazole administration there was significant improvement in STI and VER as compared to pre‐treatment values, and a significant improvement in glucagon stimulated cyclic AMP levels as compared to the levels attained after 2 months of propranolol therapy.Thus, the small fall in serum T3 produced by propranolol does not result in improved tissue thyroid function in thyrotoxicosis, whereas carbimazole brings about a dramatic improvement in peripheral hormone levels, and tissue function alike. Moreover, propranolol therapy can be hazardous in thyrotoxicosis, two patients with no previous history of heart disease developing left ventricular failure soon after its commencement.
THE SIGNIFICANCE OF THE PORTAL INSULIN SECRETION IN INSULIN DEPENDENT PATIENTS WITH RESIDUAL β‐CELL FUNCTION: A SAFEGUARD AGAINST HORMONAL AND METABOLIC DERANGEMENT
Authors: MADSBAD S. , FABER O. K. , KURTZ A. , KRARUP T. , REGEUR L. , TRONIER B. , ØRSKOV H. , BINDER C. , ALBERTI K. G. M. M. 
Published: March 2008

SUMMARYSeven insulin‐dependent patients without β‐cell function and eight with residual β‐cell function (evaluated by C‐peptide values 6 min after 1 mg of glucagon i.v.; mean 0·23, range 0·16–0·43 nmol/1) were studied during 12 h of insulin deprivation following maintenance of near‐normoglycaemia with intravenous insulin infusion. Significant differences between the two groups were found in blood glucose and 3‐hydroxybutyrate already after 3 and 4 h respectively. After 12 h the mean blood glucose concentration had reached 17·2 · SEM 1·3 mmol/l in the first group compared with 8·8 ± 1·4 mmol/l in the second group (P < 0·01) while 3‐hydroxybutyrate concentrations rose to 5·5 ± 0·5 mmol/l and 1·4±0·3 mmol/l in the two groups respectively (P<0·01).The free insulin concentration in plasma was three‐fold higher in the group without β‐cell function just before discontinuing the insulin infusion as compared with the group with β‐cell function (P<0·05). During the first 10 h of insulin deprivation no significant difference in free insulin concentration was found between the two groups. However, after 12 h of insulin deprivation all the patients with residual β‐cell function had measurable amounts of free insulin in peripheral blood, whereas in the C‐peptide negative group only the three patients with the highest amount of insulin binding antibodies had measurable free insulin concentrations.Glucagon concentrations although raised after 5 h of insulin deprivation were similar in the two groups.Mean growth hormone concentrations were higher throughout the study in the C‐peptide negative patients, while cortisol levels were significantly higher (P<0·05) after 6 h. For all the patients final cortisol concentrations were directly correlated to final blood glucose (r=0·45, P<0·05) and final blood 3‐hydroxybutyrate (r=0·67, P<0·02).The present study supports the metabolic importance of portal insulin supply to the liver and thus of residual β‐cell function. The data emphasizes the importance of the often minimal endogenous insulin reserve preserved in some insulin dependent diabetics in protection against rapid development of ketoacidosis both directly and through effects on cortisol and growth hormone secretion.
THE INTERRELATIONSHIPS BETWEEN PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING DOPAMINERGIC BLOCKAGE IN PATIENTS WITH MILD HYPERPROLACTINAEMIA WITHOUT ANY DEMONSTRABLE PITUITARY TUMOUR
Authors: SPITZ J. M. , HAAS M. , TRESTIAN S. , ZYLBER‐HARAN E. , SHILO S. 
Published: March 2008

SUMMARYPRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 μg) and LHRH (100 μg). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non‐responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean±SD basal PRL levels were 68·5 ± 29·9 ng/ml in Group I and not different in Group II (40·6±12·0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2·4±0·7 μU/ml to a peak of 5·9±2·7 μU/ml (P<0·005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide.In Group II females, PRL responsiveness to metoclopramide was associated with TSH non‐responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.
HYDROXY‐INDOLE‐O‐METHYLTRANSFERASE ACTIVITY IN HUMAN PINEALS: A COMPARISON OF CONTROLS AND SCHIZOPHRENICS
Authors: OWEN F. , FERRIER I. N. , POULTER M. , CROW T. J. 
Published: March 2008

SUMMARYThe activity of hydroxy‐indole‐o‐methyltransferase (HIOMT) has been assayed in pineal glands from fifteen controls and twenty‐three schizophrenics. There was no significant difference between the two groups in HIOMT activity and no significant effect of age, sex or neuroleptic treatment on the activity of the enzyme. A diurnal rhythm was not discernible in HIOMT activity and it is suggested that this may be the result of terminal illness. It is concluded that HIOMT activity in pineals of schizophrenics is unlikely to differ from controls.
GONADOTROPHIN RELEASING HORMONE PROVOKES PROLACTIN RELEASE IN HYPERGONADOTROPHIC HYPOGONADAL WOMEN: A RESPONSE NOT ALTERED BY DEXAMETHASONE
Authors: GEORGITIS W. J. , TREECE G. L. , HOFELDT F. D. 
Published: March 2008

SUMMARYThe prolactin response to 100 μg of intravenous gonadotrophin releasing hormone was studied in seven hypergonadotrophic hypogonadal and four eugonadal women. Prolactin rose from a mean basal level of 7·3 ± 1·6 ng/ml to a mean peak level of 20·8 ± 5·2 ng/ml in the hypogonadal women, and did not change significantly from a mean basal level of 7·7 ± 1·2 ng/ml in the eugonadal women. Dexamethasone suppression did not alter the gonadotrophin or prolactin response to GnRH.Hypergonadotrophic hypogonadal women, like some patients with acromegaly, anorexia nervosa. and anovulatory disorders, show an augmented release of prolactin after GnRH administration.
THE EVIDENCE FOR THE REGULATORY ROLE OF ENDOGENOUS GIP AS A GLUCOSE DEPENDENT INSULINOTROPIC HORMONE IN PATIENTS WITH DUODENAL ULCER
Authors: TAKEMURA J. , SEINO Y. , YAMAMURA T. , YOSHIYA K. , ISHIKAWA Y. , ITOH N. , IMURA H. 
Published: March 2008

SUMMARYIn order to investigate the mechanism of GIP secretion and the role of endogenous GIP in the enteroinsular axis in duodenal ulcer patients, we have compared plasma GIP, insulin, and blood glucose responses to oral glucose ingestion in 10 duodenal ulcer patients, 5 patients with total gastrectomy, and 20 normal subjects. The mean basal level of plasma GIP in totally gastrectomized patients was significantly higher than in normal subjects, while in duodenal ulcer patients the value was not different from that of controls. Plasma GIP and insulin responses to oral glucose loading were significantly higher than normal in both groups. The degree of exaggerated plasma GIP and insulin secretions was more prominent and earlier in totally gastrectomized patients than in duodenal ulcer patients, and was positively correlated with the blood glucose increase during glucose ingestion. On the other hand, no significant change in GIP secretion during insulin‐induced hypoglycaemia was observed in normal subjects, duodenal ulcer patients, or patients with selective proximal vagotomy. These findings indicate that the exaggerated GIP response to oral glucose in duodenal ulcer patients may be due not to increased vagal tone, but to more rapid incoming load. We found also that the hypersecretion of GIP induced by glucose ingestion in patients with duodenal ulcer and total gastrectomy may be responsible for the hyperfunction of the enteroinsular axis in these patients.
THE INTERACTION OF HUMAN ENDOMETRIAL AND MYOMETRIAL STEROID RECEPTORS WITH DANAZOL
Authors: JENKIN G. , COOKSON C. I. , THORBURN G. D. 
Published: March 2008

SUMMARYThe affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis.The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol‐17β for the oestrogen receptor was very low (1·72 ± 0·48 ± 10−3% cross reaction, mean ± SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8·41 ± 1·65% using progesterone, 1·95 ± 0·41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6·29·1±82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2·19 ± 109M‐1 and 7·45 ± 109M‐1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0·25 ± 0·06 ± 109 M‐1 and 3·62·1±67·109 M‐1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2·50 ± 0·73 ± 109 M−1. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug.
GRAVES' IMMUNOGLOBULINS PROTECT THE HUMAN TSH RECEPTOR: FURTHER EVIDENCE FOR TSH RECEPTOR ANTIBODIES IN GRAVES' DISEASE
Authors: DAVIES T. F. , PLATZER M. 
Published: March 2008

SUMMARYWe have investigated whether membrane‐bound TSH and Graves' immunoglobulins (Ig) were able to inhibit the action of the disulphide‐reducing agent dithiothreitol (DTT) which reduced the binding of 125I‐bTSH to thyroid membranes. Human thyroid (20000 g fraction) was incubated with increasing concentrations of cold bTSH, washed and resuspended in 10 mmol/1 DTT for 60 min at 37°C. After the DTT was removed, 70–80% of the receptor‐bound bTSH dissociated with 2 mol/l NaCl. In the absence of cold bTSH, 80% of the binding of receptor‐purified 125I‐bTSH was inhibited after membrane exposure to DTT but in the presence of bTSH‐occupied receptor sites there was a dose related protection of the receptors, with 100% protection following incubation with 30 mU/ml bTSH.Like bTSH, immunoglobulin fractions from Graves' sera caused a time‐dependent reduction in 125I‐bTSH binding‐inhibition after incubation and washing of thyroid membranes prior to ligand binding. Approximately 25–40% of this reduction was reversible by exposure to 2 mol/l NaCl. After pre‐binding normal Ig to thyroid membranes, and subsequent incubation with DTT, there was no protection of TSH receptors. However, each of the Graves' Ig examined (n= 4) was able to provide protection of the TSH receptor binding sites in proportion to their derived TSH receptor occupancy.Receptor‐bound bTSH was, therefore, able to protect the human TSH binding site from disulphide reduction. In addition, Graves' Ig, but not normal Ig, contained antibodies which were able to protect the TSH receptor binding sites in the same way as bTSH. These data provided evidence that Graves' Ig, but not normal Ig, contained antibodies which, when bound to the TSH receptor, appeared to affect the configuration of the TSH receptor in the same way as the binding of bTSH and protected the receptor from reduction by DTT.This evidence was consistent with graves' sera containing antibodies directed towards the TSH receptor binding site.
OUTCOME OF PATIENTS WITH GRAVES' DISEASE AFTER LONG‐TERM MEDICAL TREATMENT GUIDED BY TRIIODOTHYRONINE (T3) SUPPRESSION TEST
Authors: YAMAMOTO M. , TOTSUKA Y. , KOJIMA I. , YAMASHITA N. , TOGAWA K. , SAWAKI N. , OGATA E. 
Published: March 2008

SUMMARYThe value of the T3 suppressed 20‐min uptake test for the prediction of post‐treatment outcome was studied in 193 unselected patients with GRAVES' disease treated with thionamide drugs and T3. One hundred and twenty‐nine of 193 patients were studied previously and followed thereafter (Group A). Sixty‐four were newly treated patients: thirty‐three (Group B) were treated at the same hospital as Group A; thirty‐one (Group C) were treated at another hospital.In total, 126 patients out of 193 satisfied our criteria for suppression (total suppression rate, 65%). The suppression rate for new patients (55% in Group B, 52% in Group C) was similar to that for Group A in 1977 (49%) after comparable duration of treatment. The suppression rate for Group A increased with prolongation of the treatment period (49% in 1977 and 71% in 1981).As to the time course of suppression, it was observed that about two‐thirds of the suppressed patients satisfied the criteria for suppression within 3 years of starting treatment. The number of suppressed patients per year decreased thereafter as the treatment periods increased. However, the yearly suppression rate did not decrease with time. The time course of suppression in each patient could not be predicted from the results of initial thyroid function tests.The overall remission rate among the 120 suppressed patients followed for 1–13 (mean, 4) years was 96%, which was almost equal to the value obtained in Group A in 1977 (95%) with the average follow‐up period of 2 years. Among the 46 patients in Group A followed for 5–13 (mean, 7) years, no increase in relapse was observed with prolonged follow‐up periods. Examination on the relationship between the duration of treatment and the post‐treatment outcome
FERTILITY AFTER CHILDBIRTH: CHANGES IN SERUM GONADOTROPHIN LEVELS IN BOTTLE AND BREAST FEEDING WOMEN
Authors: GLASIER ANNA , McNEILLY A. S. , HOWIE P. W. 
Published: March 2008

SUMMARYChanges in basal serum gonadotrophin levels during the resumption of ovarian activity post partum have been studied longitudinally in breast and bottle feeding mothers. On the basis of urinary steroid levels, ovarian activity was classified as showing complete suppression, follicular activity only, deficient luteal phases or normal menstrual cycles. Complete suppression of ovarian activity during lactation was associated with normal levels of FSH but low levels of LH. The resumption of follicular development was not accompanied by any increase in levels of either LH or FSH when compared with the phase of complete suppression and this pattern persisted during menstrual cycles characterized by deficient luteal phase progesterone secretion. Basal LH levels did not rise to normal levels during lactation until the resumption of normal ovulatory cycles. FSH secretion remained at a level comparable with the follicular phase of normal ovulatory cycles throughout the post partum period.In mothers who did not breast feed, LH levels rose more rapidly than in breast feeding mothers and had returned to within normal limits by three weeks post partum. At 4 weeks post partum FSH levels were lower in bottle feeding mothers than in breast feeders probably in response to the early rise in oestrogen levels among bottle feeders.These results suggest that decreased LH but not FSH secretion may be important in maintaining infertility associated with breast feeding. The absence of any change in LH or FSH at the onset of follicular development suggests that an alteration in the sensitivity of the ovary to gonadotrophins or in the pattern of gonadotrophin secretion may be involved in the observed patterns of post partum ovarian activity during lactation.
INHIBITION OF 3‐BETA‐HYDROXY STEROID DEHYDROGENASE ACTIVITY IN FIRST TRIMESTER HUMAN PREGNANCY WITH TRILOSTANE AND WIN 32729
Authors: van der SPUY Z. M. , JONES D. L. , WRIGHT C. S. W. , PIURA B. , PAINTIN D. B. , JAMES V. H. T. , JACOBS H. S. 
Published: March 2008

SUMMARYThe effects of equivalent doses of two inhibitors of the 3‐beta‐hydroxy steroid dehydrogenase enzyme system—WIN 24540 (trilostane) and WIN 32729—on the secretion of progesterone in early human pregnancy are described. Patients and controls less than 12 weeks pregnant were given a single dose of either drug and the resultant hormonal changes monitored for 71/2 h.A consistent fall in plasma progesterone concentrations occurred at all doses and, at the highest dose, they fell to less than 50% of pre‐treatment levels. However, whilst with trilostane the associated increase in plasma concentrations of pregnenolone was always accompanied by a rise in plasma DHA concentrations, with WIN 32729 there appeared to be no adrenal effect at the lower dosage levels.These data demonstrate inhibition of progesterone secretion in human pregnancy using non‐hormonally active steroids. The pattern of steroid precursors indicates that while both drugs inhibit 3‐beta‐hydroxy steroid dehydrogenase activity, WIN 32729 is more selective and only interferes with adrenal steroid biosynthesis at high doses.