bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF MECLASTINE, A SELECTIVE H1 RECEPTOR ANTAGONIST, UPON ACTH RELEASE
Authors: ALLOLIO B. , DEUSS U. , KAULEN D. , WINKELMANN W. 
Published: March 2008

SUMMARYTo elucidate further the role of histamine in the control of ACTH secretion we investigated the effect of the selective H1 receptor antagonist meclastine on the ACTH response to insulin hypoglycaemia and to metyrapone‐induced hypocortisolaemia in normal subjects. Intravenous meclastine (4·8 mg/90 min) significantly inhibited the hypoglycaemia‐induced ACTH and Cortisol increase whereas serum GH and PRL concentrations were unaffected. Orally administered meclastine (3 × 2 mg) also reduced the ACTH feedback response to cortisol deficiency in a modified metyrapone test, compared to a placebo. Our findings support the concept of an excitatory influence of histamine upon ACTH secretion via H1 receptors, possibly by stimulation of CRF release.
HYPERTHYROXINAEMIA: ABNORMAL BINDING OF T4 BY AN INHERITED ALBUMIN VARIANT
Authors: LALLOZ M. R. A. , BYFIELD P. G. H. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYTwo euthyroid subjects with high total concentrations of T4 in their sera have been studied (J.D.: T4, 170; T3, 1·90; rT3, 0·54 nmol/1. E.T.: T4, 185; T3, 1·63; rT3, 0·37 nmol/1). Concentrations of all three T4‐binding proteins were within normal limits in both cases. However, on reverse‐flow electrophoresis an abnormally large amount of thyroxine was found to travel with albumin. The three T4‐binding proteins in the sera of both patients were separated from each other by a novel affinity chromatographic method using dye‐Sepharose conjugates. Affinity constants for T4 binding to TBG and to prealbumin from both patients were normal. The albumin preparations were further purified and shown by physical and immunochemical techniques to be uncontaminated by other proteins. Scatchard plots of the binding of T4 to each of these pure albumins revealed two components, one having a normal affinity constant (J.D., 1·8 ± 105 lmol−1 and E.T., 2·3 × 105 lmol−1), the other having a raised affinity constant (J.D., 5·4 × 106 lmol−6 and E.T., 5·8 × 106 lmol−1). Extrapolation of the plots showed that the high affinity components comprised 66% (J.D.) and 54% (E.T.) of the total purified albumin. The raised affinity and high concentrations of the variants thus account for the raised total T4 concentrations in the patients. The presumed amino acid substitution in the albumins may be different in the two patients since the affinities for rT3 differ. Some methods for the estimation of free T4 levels give misleading results in the presence of these albumin variants. In the course of two episodes of illness, patient J.D. manifested large falls in serum T4 levels which could only be accounted for by reduced carriage of T4 by the abnormal and conventional binding proteins. Many cases reported in the literature as partial peripheral resistance to thyroid hormone may be examples of similar albumin variants.
CORTICOSTEROID MYOPATHY: A CLINICAL AND PATHOLOGICAL STUDY
Authors: KHALEELI A. A. , EDWARDS R. H. T. , GOHIL K. , McPHAIL G. , RENNIE M. J. , ROUND J. , ROSS E. J. 
Published: March 2008

SUMMARYIn six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24‐h urinary 3‐methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.
STUDIES OF IMMUNOGLOBULIN SYNTHESIS IN CULTURES OF PERIPHERAL T AND B LYMPHOCYTES: REDUCED T‐SUPPRESSOR CELL ACTIVITY IN GRAVES’DISEASE
Authors: PACINI FURIO , DeGROOT LESLIE J. 
Published: March 2008

SUMMARYCellular interactions involved in Graves’disease were studied in patients in different stages of the disease and in normal controls. Synthesis and secretion of immunoglobulin G (IgG) in the supernate of pokeweed mitogen (PWM)‐stimulated cultures of constant numbers of non E rosette forming cells (E− cells) and of increasing numbers of autologous E rosette forming cells (E+ cells) (E+/E− ratios = 1:1, 2:1, 4:1, 8:1, 10:1) were measured by a specific solid‐phase radioimmunoassay. In the normal group, the mean IgG production increased with increasing E+/E‐ ratio (T helper effect), reaching a maximum at a T/B ratio of 4:1, then decreased at higher E+/E− ratios (T suppressor effect). At a E+/E− ratio of 10:1 the IgG synthesis was 39% of the peak value. In the Graves’patients the mean IgG synthesis increased with increasing numbers of E+ cells at every ratio with a peak value found at E+/E− ratio = 10:1. There was no detectable suppressor effect. In three experiments performed with allogeneic combinations of cells, it was observed that the Graves’E− cells were able to respond both to helper and suppressor signals from normal E+ cells, while the Graves’E+ were not able to suppress IgG synthesis by normal E− cells. Treatment of E+ cells with 3,000 cGy of irradiation before adding them to E− cells abolished the suppressor effect seen at the higher E+/E− ratios in the normal controls because of inactivation of the T suppressor lymphocytes. In contrast, the same procedure was without effect on the IgG synthesis by E− cells in Graves’patients. When peripheral blood mononuclear cells (PBMC) were cultured in the presence of PWM and of PWM + Concanavalin‐A (Con‐A), the PWM‐induced synthesis of IgG was suppressed in the presence of Con‐A by 75% (using unfractionated PBMC) and 74% (using E+/E− cells) at 1:1 ratio in normal controls, while Graves’patients’cells caused lower suppression of 66 and 48%, respectively. This latter value was significantly different from that found in the normal group (P < 0·05).
COMPARISON OF PREOPERATIVE AND POSTOPERATIVE ACTH CONCENTRATIONS AFTER BILATERAL ADRENALECTOMY IN CUSHING'S DISEASE
Authors: BARNETT A. H. , LIVESEY J. H. , FRIDAY KAREN , DONALD R. A. , ESPINER E. A. 
Published: March 2008

SUMMARYUp to one‐third of subjects who have had bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. To examine the value of pre‐operative ACTH assays in predicting outcome, we have studied fifteen cases of Cushing's disease treated by bilateral adrenalectomy and pituitary irradiation. Three patients developed Nelson's syndrome. There was no significant correlation between preoperative ACTH level, either 8 am ‘basal’or during metyrapone testing, and ACTH concentration post‐treatment. Plasma ACTH concentration in the first year after treatment, however, showed a highly significant correlation with the latest postoperative value (n= 14, r= 0·684, P < 0·01), even more marked when subjects with duration of follow‐up < 3 years were excluded (n= 11, r= 0·836, P < 0·002). In nine of fifteen patients, plasma ACTH showed either no change or a definite fall during subsequent follow‐up. We conclude that plasma ACTH measurement in the first post‐operative year is a good indicator of eventual outcome. The continued fall in plasma ACTH shown in many patients after the first year of treatment suggests an effect of irradiation on the pituitary.
DOPAMINERGIC CONTROL OF GONADOTROPHIN SECRETION IN NORMAL WOMEN AND IN PATIENTS WITH PATHOLOGICAL HYPERPROLACTINAEMIA
Authors: HO K. Y. , SMYTHE G. A. , LAZARUS L. 
Published: March 2008

SUMMARYThe role of dopaminergic mechanisms in the control of gonadotrophin secretion in normal and hyperprolactinaemic subjects is controversial. Whilst bromocriptine, a potent dopamine agonist, has been used to restore normal gonadotrophin secretion in subjects with pathological hyperprolactinaemia (PHP), dopamine and dopamine agonists have been reported to suppress basal and stimulated gonadotrophin release. We therefore investigated the importance of dopaminergic control of gonadotrophin secretion by studying LH, FSH and PRL responses in normal and PHP subjects to central dopamine synthesis inhibition using monoiodotyrosine (MIT) and to a 4 h dopamine infusion designed to elevate peripheral plasma dopamine concentration to levels reported for pituitary portal plasma (1–6 ng/ml). MIT administration resulted in a significant release of PRL (peak increment 520 ± 84% above basal) but not of LH or FSH in normal subjects. In PHP subjects there was a blunted PRL response (peak 13·3 ± 3·5%) to MIT administration and significant LH (P<0·05) but not FSH release. Dopamine infusion (0·5 μg/kg/min) resulted in suppression of PRL (min 19 ± 3% of basal) but not of LH or FSH. A rebound of PRL (peak 188 ± 68% of basal) but not LH or FSH occurred on cessation of dopamine. There was an apparent rise in LH (P < 0·02 vs. normals) but not FSH in PHP patients during dopamine infusion. Plateau dopamine levels achieved during the infusion were 2·9 ± 0·3 ng/ml and 5·9 ± 0·8 ng/ml in normal and PHP subjects respectively. The responses to MIT show that dopamine functions as an inhibitor of PRL but not of LH or FSH in normal subjects. In PHP patients the responses suggest increased dopaminergic inhibition of LH release but loss of inhibitory control of PRL release. Physiological concentrations of plasma dopamine do not significantly inhibit LH or FSH release in normal subjects but paradoxically results in an apparent release of LH in PHP patients. We conclude that dopamine mechanisms do not play a significant role in modulating gonadotrophin release in normal subjects. In PHP patients, PRL feedback
THE EFFECT OF DYDROGESTERONE ON THE MID‐CYCLE GONADOTROPHIN SURGE IN REGULARLY CYCLING WOMEN
Authors: LENTON ELIZABETH A. 
Published: March 2008

SUMMARYThe effect of dydrogesterone, a retro‐progesterone on the spontaneous mid‐cycle surge of gonadotrophin in regularly cycling women, was investigated. Blood samples were collected through two complete cycles in six subjects. The first untreated cycle acted as a control for the second cycle during which dydrogesterone (10 mg twice daily) was administered. The start of treatment ranged from day 1 (one subject), mid follicular phase (three subjects) to post‐ovulation (two subjects). In all subjects where dydrogesterone was given before ovulation, the mid‐cycle gonadotrophin surge was either abolished or markedly diminished. Despite this follicular growth occurred in all four subjects and subsequently luteinisation was observed in three. Dydrogesterone given after ovulation did not produce any alteration in endocrine profiles but menses was postponed in both subjects.Thus dydrogesterone can mimic the known blocking actions of progesterone on the mid‐cycle gonadotrophin surge and can support a secretory fehdometrium for a limited period in the absence of endogenous progesterone.
SCREENING FOR MULTIPLE ENDOCRINE NEOPLASIA SYNDROME (TYPE 1) IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM
Authors: MUHR C. , LJUNGHALL S. , ÅKERSTROM G. , PALMÉR M. , BERGSTRÖM K. , ENOKSSON P. , LUNDQVIST G. , WIDE L. 
Published: March 2008

SUMMARYIn 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma‐(MEN)‐syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG‐α and β). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN‐1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo‐ or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG‐α and β levels were within the normal range in all patients but two. We conclude that the incidence of MEN‐1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.
PITUITARY RESPONSIVENESS TO GONADOTROPHIN‐RELEASING AND THYROTROPHIN‐RELEASING HORMONES IN EPILEPTIC PATIENTS RECEIVING CARBAMAZEPINE OR PHENYTOIN
Authors: DANA‐HAERI J. , OXLEY J. , RICHENS A. 
Published: March 2008

SUMMARYPituitary responsiveness to gonadotrophin‐releasing (LHRH) and thyrotrophin‐releasing (TRH) hormones was studied in 19 epileptic patients receiving long‐term carbamazepine or phenytoin therapy and 14 normal control subjects. Baseline prolactin levels were normal in the patients; 2 h after LHRH‐TRH the prolactin levels in women on carbamazepine were significantly higher than in the controls, but apart from this, no other differences were found. Baseline LH levels were raised in male patients and the response to LHRH‐TRH was exaggerated in all patients on carbamazepine. FSH levels were normal throughout. The exaggerated LH response is consistent with primary hypogonadism caused by enhanced sex hormone metabolism, secondary to hepatic enzyme induction by the antiepileptic drugs.
A STUDY OF THE RELATIONSHIP BETWEEN CIRCULATING β‐ENDORPHIN‐LIKE IMMUNOREACTIVITY AND POST PARTUM ‘BLUES’
Authors: NEWNHAM J. P. , DENNETT PATRICIA M. , FERRON SUZANNE A. , TOMLIN SUSAN , LEGG C. , BOURNE G. L. , REES LESLEY H. 
Published: March 2008

SUMMARYPlasma β‐endorphin‐like immunoreactivity was studied in 43 pregnant women at 36 weeks gestation and in 23 of these at delivery and 24 h post‐partum; an attempt made to correlate changes with various social, psychological and obstetric factors, including the ‘post‐natal blues’. β‐endorphin levels were elevated at 36 weeks gestation and term, increased to very high levels during labour and fell rapidly within 1 h of delivery. A negative correlation was observed between the woman's estimate of her pain in labour and the β‐endorphin levels post‐partum, suggesting an analgesic role for β‐endorphin in labour. A positive correlation was also observed between the levels of β‐endorphin at delivery and the woman's attitude to her pregnancy at 36 weeks and a negative correlation between the ‘post‐natal blues score’ and the β‐endorphin level at 36 weeks. However, the ‘blues’ did not correlate either with the β‐endorphin level at delivery or 24 h post‐partum nor with its rate of fall in the first 24 h. Our general finding that there was no consistent social, psychological or obstetric factor which predisposes women to develop ‘post‐natal blues’ still supports the hypothesis that humoral factors, of which β‐endorphin may be one, rather than psychological factors are important in the genesis of this syndrome.
17β‐HYDROXYSTEROID DEHYDROGENASE AND AROMATASE ACTIVITY IN BREAST FAT FROM WOMEN WITH BENIGN AND MALIGNANT BREAST TUMOURS
Authors: BERANEK P. A. , FOLKERD E. J. , GHILCHIK M. W. , JAMES V. H. T. 
Published: March 2008

SUMMARYThe activity of 17β‐hydroxysteroid dehydrogenase and aromatase was studied in adipose tissue taken from women aged between 22 and 83 years with benign or malignant breast lesions. The benign and malignant groups showed no significant differences in the mean activities of either of the enzymes studied. Under the experimental conditions used, the rate of conversion of oestrone to oestradiol varied markedly between subjects (6‐169 ng oestradiol/mg protein/h), and there was a positive correlation between oestrone reduction and the total body weight of the tissue donor. In contrast, although the apparent Km for oestradiol (0·1–2·6 μmol/1) was lower than that for oestrone (9–14 μmol/1) the maximum velocity for oestrone production was very low (10–50 pmol/mg protein/h), and there was no obvious correlation with the age or body weight of the tissue donor. Aromatase activity in breast fat was at the lower end of the normal range of activity previously reported for abdominal adipose tissue, and there was no correlation between oestrone production and age or body weight.
INCREASED PLASMA CONCENTRATION OF N‐TERMINAL β‐LIPOTROPHIN AND UNBOUND CORTISOL DURING PREGNANCY
Authors: ABOU‐SAMRA A. B. , PUGEAT M. , DECHAUD H. , NACHURY L. , BOUCHAREB B. , FEVRE‐MONTANGE M. , TOURNIAIRE J. 
Published: March 2008

SUMMARYThe plasma concentration of N‐terminal β‐lipotrophin (β‐LPH), total and protein unbound cortisol, progesterone and the transcortin (CBG) binding parameters have been measured in 21 women in the early follicular phase and in 70 pregnant women at various stages of pregnancy. Results showed that the plasma CBG binding capacity and the concentrations of total cortisol and progesterone increased significantly at each trimester of pregnancy while the plasma concentration of unbound cortisol increased significantly only in the 2nd and the 3rd trimesters of pregnancy. In addition, a significant increase of N‐terminal β‐LPH level was observed during the 3rd trimester. By chromatography, it is demonstrated that during the 3rd trimester of pregnancy the β‐LPH/γ‐LPH molar ratio decreases dramatically and that the increase of N‐terminal β‐LPH concentration is mainly due to a two fold increase in γ‐LPH concentration.
IN VITRO GENERATION OF NADPH AS AN INDEX OF THYROID STIMULATING IMMUNOGLOBULINS (TGI) IN GOITROUS DISEASE
Authors: McMULLAN N. M. , SMYTH P. P. A. 
Published: March 2008

SUMMARYA quantitative cytochemical assay for the measurement of total NADPH formation in guinea pig thyroid tissue following incubation with thyroid stimulators was validated and applied to the measurement of such stimulators in IgG concentrates prepared from human plasma. Pentose shunt enzyme activity was not uniformly distributed in thyroid tissue but this could be overcome and NADPH generation in such tissue used to assess accurately thyroid stimulators if a sufficient number of thyroid cells were measured. Specificity studies showed that antiserum to human IgG significantly diminished the NADPH generating capacity of IgG concentrates prepared in plasma from goitrous patients while antiserum to h‐TSH had no such effect. The measurement of thyroid growth stimulating immunoglobulins (TGI) depended not only on the amount of NADPH generated but also on the IgG concentration at which maximum responses occurred. TGI present in goitrous GRAVES' disease were 10 times more potent than those present in euthyroid goitre, while such stimulators when present in toxic nodular goitre appeared to possess an intermediate potency. This finding, when taken together with the demonstration that TSH stimulation decreased intercellular differences in pentose shunt activity, provides experimental evidence for the hypothesis that an acute intense growth stimulus affecting all thyroid cells produces the diffuse hyperplasia characteristic of GRAVES' disease. In contrast, the weaker stimulus observed in nodular goitre may, over a period of time, result in the asymmetric hyperplasia commonly observed in this condition.
ENDEMIC INFANTILE HYPOTHYROIDISM IN A SEVERE ENDEMIC GOITRE AREA OF CENTRAL AFRICA
Authors: VANDERPAS J. , BOURDOUX P. , LAGASSE R. , DRAMZAIX M. , LODY D. , NELSON G. , DELANGE F. , ERMANS A. M. , THILLY C. H. 
Published: March 2008

SUMMARYThyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 ± 4 nmol/1) and stayed at that level during the first year of life (123 ± 9) (NS), but decreased to 75 ± 8 (P < 0·001) at 2–4 years and to 62 ± 6 (P < 0·001) at 5–7 years of age. Mean serum FT4 decreased from 10·4 ± 0·9 pmol/1 during the first year to 8·2 ± 1·0 (NS) at 2–4 years (NS) and to 7·7 ± 0·9 (P < 0·05) at 5–7 years. Mean serum TSH was 10·4 (8·4‐12·9) m U/1 (geometric mean ± 1 SEM) during the first year, 10·1 (7·5‐13·7) (NS) at 2–4 years and 24·3 (18·5–31·9) (P < 0·05) at 5–7 years. Mean serum T3 was 3·23 ± 0·12 nmol/1 during the first year and remained stable thereafter. The frequencies of low T4 (T4 < 77 nmol/1), high TSH TSH (TSH > 50 mU/1), and low T4 and T3 (T3 < 1·69 nmol/l) were twice as high at 5–7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 ± 5 ųmol/1) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 ųmol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 ± 7 ųmol/l) in the mothers' serum but low in the mothers' milk (57 ± 3 ųmol/1) (P < 0·01). Multivariate analysis
MEASUREMENT OF FREE THYROXINE AND FREE TRIIODOTHYRONINE IN ASYMPTOMATIC SUBJECTS WITH HIGH CONCENTRATIONS OF SERUM TSH AND A HISTORY OF RADIOIODINE THERAPY
Authors: FRANKLYN J. A. , SHEPPARD M. C. , RAMSDEN D. B. , HOFFENBERG R. 
Published: March 2008

SUMMARYTotal and free thyroid hormones were measured in a group of asymptomatic subjects with high circulating TSH concentrations and a previous history of radioiodine therapy. Subjects in the high TSH group all fell within the normal range for measurements of total T4, total T3 and T4/TBG ratio. Concentrations of free T4 or free T3 were below the normal range in more than half (9 out of 17) of the high TSH group suggesting that these measurements are more sensitive indices of thyroid failure than measurement of total hormones or T4/TBG ratio.Hypothyroidism is a common complication of the treatment of thyrotoxicosis with radioiodine, the cumulative incidence 15 years after treatment reaching 80% in some centres (Greig, 1973). Although considered a good index of impaired thyroid function, a high serum TSH is commonly observed after radioiodine therapy and may persist for some years in subjects judged euthyroid by other criteria (Toft et al., 1975). We have recently demonstrated the value of measurements of free T4 and free T3 in the routine diagnosis of thyroid dysfunction (Franklyn et al., 1984) and in the present study we have compared these measurements with other parameters of thyroid function in a group of asymptomatic subjects with high circulating TSH concentrations and a history of radioiodine therapy.