bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovation and Corporate Mergers
Authors: Davidson Kenneth M.
Published: March 2008

It is common to identify cultural differences between the acquired and acquiring firms as the cause of the failure of individual mergers. For example, H. Ross Perot, the head of Electronic Data Systems, found it impossible to function after General Motors acquired his firm. Many blamed the clash in cultures between an old‐line, bureaucratic manufacturing firm and an innovative, flexible computerage firm.
Strategies for Creativity
Authors: Sonnenberg Frank K.
Published: March 2008

When was the last time that someone from your organization came up with a good idea? Do you reward innovation or stifle it with politics, protocol, and procrastination? Do you have a formal plan for stimulating ideas or just allow them to happen? Do senior managers break down old barriers or construct new ones?
A Vision to Look Beyond Cost Control
Authors: Vajta Peter G.
Published: March 2008

Whether driven by a desire to thwart the advances of unwanted investors playing the buyout game or driven by the pressure of new and global competitors, U.S. industry has embraced cost cutting as a way of life . . . and the good old days will never return. Although the frantic leveraged buyouts of the 1980s have abated, they have been replaced by fears of recession, while competitive pressures continue to build. The response? Management intensifies its relentless attack on costs and maintains a single‐minded focus on streamlining its operations.
Effect of Erythropoietin Therapy on the Red Cell Volume of Uraemic and Non‐uraemic Rats
Authors: Anagnostou A. , Barone J. , Kedo A. , Fried W.
Published: March 2008

Summary. Studies were performed to determine the effect of injecting repeated doses of erythropoietin (Ep) on the red cell volume of chronically uraemic rats and on that of non‐uraemic sham operated ones. After 13 doses of Ep (5 u/dose), started either 5 or 21 d after removal of five‐sixths of the renal mass, the increase in the red cell volume of uraemic rats was as great as that of non‐uraemic ones. The significance of these results is discussed.
TUMOUR AND PLASMA ACTH CONCENTRATIONS IN PATIENTS WITH AND WITHOUT THE ECTOPIC ACTH SYNDROME
Authors: RATCLIFFE J. G. , KNIGHT R. A. , BESSER G. M. , LANDON J. , STANSFELD A. G.
Published: March 2008

Bioactive and immunoreactive corticotrophin (ACTH) concentrations in seventeen tumours from patients with the ectopic ACTH syndrome were compared with those in fourteen ‘control’tumours from patients without the syndrome. Each of the ‘control’tumours showed ACTH activity greater than in non‐tumorous tissue and the range of concentrations overlapped with the ‘ectopic ACTH’group. The presence of significant ACTH activity in every tumour studied suggests that hormone production may be a common feature of neoplasia in the absence of clinically obvious sequelae of excess circulating hormone. Tumours associated with the ectopic ACTH syndrome showed a wide range of ACTH activities: bronchial carcinoid tumours generally contained higher levels than oat cell carcinomas of the bronchus and more C‐ than N‐terminal ACTH activity. In twenty‐four patients with the clinical syndrome the plasma ACTH levels were not clearly related to tumour type; the levels ranged between 100 and 10,000 pg/ml, showed an abnormal nyctohemeral rhythm, and fell following successful removal of the tumour.
SUBCUTANEOUS GLUCAGON AS A TEST OF THE ABILITY OF THE PITUITARY TO SECRETE GH AND ACTH
Authors: SPATHIS G. S. , BLOOM S. R. , JEFFCOATE W. J. , MILLAR J. G. B. , KURTZ A. , PYASENA M. R. D. , SMITH JEANNE A. , NABARRO J. D. N.
Published: March 2008

The response to the subcutaneous injection of glucagon (1 mg) has been studied as a test of the ability of the pituitary to secrete ACTH and growth hormone (GH). Tests have been performed on fifteen normal subjects or patients with unrelated conditions, nine patients with pituitary tumours and seventeen with acromegaly. It is suggested that a normal response is a peak level of 5 ng/ml or more of GH (standard NIH GH 1216C) and either a rise of plasma cortisol measured by competitive protein binding of at least 4 μg/100 ml or a peak level of 7 μg/100 ml. In seventeen patients the responses were compared with those obtained in the insulin hypoglycaemia test and there was good agreement. Measurement of plasma ACTH showed that the response is at pituitary and not adrenal cortical level. Peak responses of ACTH and GH were obtrained at 150 min and of cortisol at 180 min. Plasma glucagon concentrations were falling steadily by this time although still above the control level. The mechanism of action of glucagon is not clear but does not appear to be related to fall of blood sugar. The subcutaneous injection of glucagon is not without side effects; about half the patients were nauseated and nine vomited. Nevertheless we believe that a subcutaneous glucagon test is of value for testing the pituitary reserve of ACTH and GH in situations where insulin hypoglycaemia cannot be used.
THE EFFECT OF THE INTESTINAL POLYPEPTIDES, IRP AND GIP, ON INSULIN|RELEASE AND GLUCOSE TOLERANCE IN THE BABOON
Authors: TURNER D. S. , ETHERIDGE LAURAINE , JONES JULIE , MARKS V. , MELDRUM B. , BLOOM S. R. , BROWN J. C.
Published: March 2008

The recently isolated intestinal polypeptides, intestinal insulin releasing polypeptide (IRP) and gastric inhibitory polypeptide (GIP), have been shown to potentiate glucose stimulated insulin release in the baboon. The effect was similar to that seen in the rat and demonstrates that both peptides affect insulin release in a broad range of species. No effect on glucagon release was observed. The possibility that either IRP or GIP, or both, is involved in the alimentary augmentation of insulin release by oral glucose deserves consideration.

It is now well recognized that intestinal hormones are concerned in the regulation of glucose homeostasis (McIntyre et al., 1964; Marks & Samols, 1970), but their absolute identity and relative importance is uncertain.

Two recently isolated polypeptides, intestinal insulin releasing polypeptide (IRP) (Turner, 1972; Turner et al., 1973) and gastric inhibitory polypeptide (GIP) (Brown et al., 1969), have been shown to produce dramatic effects on the insulinaemic response to intravenous glucose in the rat (Turner et al., 1973; Dupré, 1973). In order to determine whether these effects are limited to the rat, or a general phenomenon, the ability of the two peptides to augment the insulin response to intravenous glucose was examined in the baboon, Papio papio. In view of the known suppressive effect of oral glucose on glucagon release, plasma glucagon levels were also measured.
THE EFFECTS OF LARGE DOSES OF THE ANABOLIC STEROID, METHANDROSTENOLONE, ON AN ATHLETE
Authors: KILSHAW B. H. , HARKNESS R. A. , HOBSON B. M. , SMITH A. W. M.
Published: March 2008

Doses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete.

The administration of the durg has been checked and its metabolism studied from the pattern of urinary metabolites.
ON THE METABOLISM OF TWO ADRENOCORTICOTROPHIN ANALOGUES
Authors: BAKER JOHN R. J. , BENNETT HUGH P. J. , HUDSON ANNE M. , MARTIN COLIN Mc , PURDON GILLIAN E.
Published: March 2008

The metabolism of Synacthen® (corticotrophin‐(1–24)‐tetracosapeptide) and C‐41795‐Ba ([d‐Ser1, Lys17, Lys18]‐corticotrophin‐(1–18)‐octadecapeptide amide) have been compared in the rat following intravenous injection. Using Synacthen and C‐41795‐Ba labelled with tritium it was possible to follow the tissue distribution of the two peptides. The kidney was shown to concentrate intact peptide and fragments of both peptides. Autoradiography of perfused kidney sections demonstrated the uptake of radioactivity into the lysosomes of the kidney proximal tubule cells. Comparison of the distribution of radioactive products formed from the tetracosapeptide labelled in different positions indicates that, prior to renal uptake, metabolism is taking place at other sites in the body. It is suggested that rapid cleavage occurs extracellularly at or near the N‐ and C‐termini. Then large fragments remaining in the circulation, together with any intact material, are filtered through the glomerulus and are taken up by endocytosis into the proximal tubule cells of the kidney. The synthetic N‐ and C‐terminal protection of the octadecapeptide appears to inhibit the extracellular attack and so the concentration of intact peptide in the kidneys is initially higher than the tetracosapeptide. Although concentrations of radioactivity in other tissues are low in comparison with the kidneys, the quantities are quite high when the weight of the tissues are considered. Chromatographic analysis of this radioactivity reveals that the octadecapeptide gives rise to much higher tissue levels of intact peptide and we believe that this acts as a depot and gives rise to the sustained blood concentrations and prolonged biological effects observed with this peptide.
THYROXINE BINDING GLOBULIN DEFICIENCY IN A FAMILY WITH TYPE I HYPERLIPOPROTEINAEMIA
Authors: LAMBERTS S. W. J. , CASPARIE A. F. , MIEDEMA K. , HENNEMANN G. , HULSMANS H. A.M.
Published: March 2008

A familial type I hyperlipoproteinaemia is described in three members of a family of eleven; on the basis of LPL activity and HDL content of plasma three other members of the family have been diagnosed to be heterozygotes without other disturbances in their lipid spectrum. The distribution of this lipid disorder is in accordance with an autosomal recessive inheritance pattern. In this family a second hereditary condition, thyroxine binding globulin deficiency, was found in addition to the hyperlipoproteinaemia. The inheritance of this condition appears to be as an autosomal dominant. An interrelated inheritance pattern of both conditions could not be proved, but both traits may be located on the same chromosome at some distance from another to allow recombination.
NEUROENDOCRINE CONTROL OF PROLACTIN IN EXPERIMENTAL ANIMALS
Authors: MEITES JOSEPH
Published: March 2008

Hypothalamic regulation of prolactin secretion in animals (mammals) and man appears to be similar, and no significant differences have yet been demonstrated. The hypothalamus contains neurotransmitters and polypeptides that can either inhibit or stimulate prolactin release, although the predominant influence under basal conditions is to inhibit prolactin release. Thus pituitary stalk section or placement of lesions in the basal tuberal region of the hypothalamus results in increased prolactin release and sometimes in initiation of lactation. Among agents in the hypothalamus that can inhibit prolactin release, the most important appear to be an as yet unidentified polypeptide prolactin release inhibiting factor (PIF) and dopamine. There is some evidence that dopamine may account for most, if not all, of the prolactin release inhibiting activity of the hypothalamus. Agents that increase dopamine activity, i.e. L‐dopa, monoamine oxidase inhibitors, etc., depress prolactin release. Acetylcholine also can inhibit prolactin release, but it appears to act via the catecholamines. Of the agents in the hypothalamus that stimulate prolactin release, the most important appear to be an as yet uncharacterized polypeptide prolactin releasing factor (PRF), thyrotropin releasing hormone (TRH) and serotonin. TRH is as effective in releasing prolactin as in releasing TSH, but under most physiological states, TSH and prolactin release do not occur together. Serotonin and its precursors, tryptophan and 5‐hydroxytryptophan, are powerful releasors of prolactin and have been shown to be involved in some physiological states in which prolactin is released, i.e. during suckling, stress, etc. Other agents in the hypothalamus that can stimulate prolactin release include GABA and some prostaglandins, but these have not yet been shown to be involved in physiological control of prolactin secretion. Exteroceptive stimuli that alter prolactin release act through the CNS and hypothalamus, but some hormones and drugs also can act directly on the pituitary to promote or depress prolactin release.
EFFECT OF lα‐HYDROXYVITAMIN D3 AND 1,25‐DIHYDROXYVITAMIN D3 ON INTESTINE AND BONE IN GLUCOCORTICOID‐TREATED PATIENTS
Authors: LUND B. , ANDERSEN R. B. , FRIIS T. , HJORTH L. , JØRGENSEN F. S. , NORMAN A. W. , SØRENSEN O. H.
Published: March 2008

The effect of lα‐hydroxyvitamin D3 (lα‐OHD3) and 1,25‐dihydroxyvitamin D3 (1,25–(OH)2D3) on the intestinal calcium absorption was studied in twenty patients with rheumatoid arthritis treated with prednisone at daily doses of 5–15mg for 1/2–20 years. The fractional calcium absorption, measured before and after the treatment with the vitamin D compounds, increased in nineteen of the twenty patients. This was, however, accompanied by marked rises in the urinary calcium excretion. There was no correlation between the fractional calcium absorption and the duration of the prednisone treatment or the doses given.
MEASUREMENT OF THYROID SIZE BY ULTRASOUND, PALPATION AND SCINTISCAN
Authors: TANNAHILL A. J. , HOOPER M.J. , ENGLAND MYSIA , FERRISS J. B. , WILSON G. M.
Published: March 2008

Thyroid gland size was calculated from grey‐scale ultrasound images in twenty patients with goitre. Results were compared with measurements by palpation and in some cases with measurements by scintiscan and at operation. There was a good correlation between ultrasound measurements and both the size of surgical specimens and clinicians' estimations, although clinicians under‐estimated the size of large (> 40 ml) goitres compared with ultrasound and surgical specimens. Gland size calculated from scintiscan did not correspond well with measurements by ultrasound or palpation.
ADRENOLEUKODYSTROPHY: REPORT OF A FAMILIAL CASE
Authors: FETTES I. , KILLINGER D. , VOLPÉ R.
Published: March 2008

Adrenoleukodystrophy is an unusual disorder in which progressive diffuse demyelination of the cerebrum is associated with adrenal insufficiency, and which is transmitted as a sex‐linked recessive trait. This report describes a 36‐year‐old male, who first presented 12 years previously with hypogonadotrophic hypogonadism. It is only more recently that he has developed primary adrenal insufficiency, as well as a neurological disorder characterized by cerebellar, pyramidal tract and cerebral cortical abnormalities. One brother died at age 7 with Schilder's disease, while another brother suffered adrenal insufficiency, progressive mental and neurological deterioration and death at age 38, with post‐mortem evidence of adrenoleukodystrophy. Histological studies have revealed cytoplasmic striated inclusions, which proved to be lipid in nature, but the precise defect in lipid metabolism has yet to be clarified.
TWENTY‐FOUR HOUR PROFILES OF CIRCULATING ANDROGENS AND OESTROGENS IN MALE PUBERTY WITH AND WITHOUT GYNAECOMASTIA
Authors: LARGE D. M. , ANDERSON D. C.
Published: March 2008

The possible mechanisms involved in the development of transient gynaecomastia during male puberty have been investigated by studying 24 h profiles of circulating androstenedione (Ao) and testosterone (T) and their oestrogen pairs oestrone (E1) and oestradiol (E2), in eight boys with simple delayed puberty, eleven boys with pubertal gynaecomastia (three of whom were re‐tested after its spontaneous resolution), and two normal adult men.

No differences were observed between the 24 h T and Ao profiles of pubertal boys with or without gynaecomastia; we confirmed that the initial T rise was nocturnal, associated with sleep. Late in puberty daytime T levels also rise. A small rise in 24 h Ao was seen, but this was not closely related to the stage of puberty. The major new finding was that E2 and to a lesser extent E1 levels are high relative to T for prolonged periods of the afternoon and evening (when T levels are lowest) in male puberty. A frequent finding, seen only in boys with gynaecomastia and one who later developed it, was of elevated and markedly fluctuating levels of plasma E2, and an absolute increase in the area under the 24 h E2 profile and between the E2 and T profiles. These fell towards normal in three boys who were re‐tested after resolution of gynaecomastia. In a minority of subjects T and E2 were quite closely correlated, suggesting that in them rapid aromatization of T was occurring within or outside the testis.

We conclude that normal male puberty is associated with relative oestrogen dominance particularly in the daytime. In boys with gynaecomastia there is in addition often an absolute elevation of E2 with or without E1, while 24 h T levels are submaximal. Normal men probably require sustained adult circulating T levels to prevent their oestrogens from stimulating breast development.
THE EFFECT OF LONG‐TERM DIPHENYLHYDANTOIN THERAPY ON GLUCOSE TOLERANCE AND INSULIN SECRETION: A CONTROLLED TRIAL
Authors: PERRY‐KEENE D. A. , LARKINS R.G. , HEYMA P. , PETER C. T. , ROSS D. , SLOMAN J. G.
Published: March 2008

The influence of long‐term administration of diphenylhydantoin (DPH) on glucose tolerance and insulin secretion was studied in a random controlled trial in non‐epileptic patients receiving the drug for 2 years following recovery from myocardial infarction. While receiving DPH, insulin response to glucose was less than that in the control group, both in absolute terms and when related to the blood glucose level. Despite this, glucose tolerance did not differ from the control group. One month after cessation of DPH, the plasma insulin response had returned to the levels found in the control group, and glucose tolerance had improved to be significantly better than that found in the control group. Thus, the tendency of DPH to impair the insulin response to glucose has been confirmed in this controlled study. However, this does not result in significantly impaired glucose tolerance; it is suggested that the decreased insulin secretion is accompanied by improved insulin sensitivity.
A GONADOTROPHIN RESPONSIVE TESTOSTERONE PRODUCING ADRENOCORTICAL ADENOMA AND HIGH GONADOTROPHIN LEVELS IN AN ELDERLY WOMAN
Authors: DE LANGE W. E. , PRATT J. J. , DOORENBOS H.
Published: March 2008

A gonadotrophin responsive testosterone producing adrenal cortical adenoma in a 61–year‐old woman is described. Oophorectomy was performed before adrenalectomy as at first an ovarian origin of excess androgen production was suspected. The hypophyseal gonadal feedback system was studied after oophorectomy using LHRH before and after administration of ethinyloestradiol. After adrenalectomy this study was repeated using ethinyloestradiol at two dose levels and after premedication with testosterone. In this patient the LH feedback system behaved similarly to that observed in Klinefelter's syndrome and in patients with anorchia.
MEASUREMENT OF 3′‐MONOIODOTHYRONINE IN HUMAN SERUM
Authors: CORCORAN J. M. , EASTMAN C. J.
Published: March 2008

An heterologous radioimmunoassay for measurement of 3′‐monoiodothyronine (3′T1) has been developed using pure 3′T1 as standard, (125I) DL3′T1 and an anti 3,3′L‐diiodothyronine antiserum. The assay utilizes Sephadex G25F minicolumns to separate 3′T1 from other endogenous iodothyronines. 8‐ani‐lino‐1‐naphthalene sulphonic acid was used to inhibit binding of 3′T1 to serum binding proteins. Sensitivity was approximately 3·2 pmol/l. The mean serum 3′T1 concentration was 7·4 pmol/l in normal subjects, 30·8 pmol/l in thyrotoxic patients, 4·1 pmol/l in hypothyroid patients, 23·2 pmol/l in patients with severe non‐thyroidal illness and 109·8 pmol/l in cord blood. Increased levels of 3′T1 were found in two normal volunteers who were injected with 3,3′T2, demonstrating that 3′T1 is derived from 3,3′T2 in extrathyroidal tissues. These studies suggest that 3′T1 is a minor iodothyronine metabolite in the human. It is unlikely to have significant biological relevance.
SERUM LIPIDS, POSTHEPARIN PLASMA LIPASE ACTIVITIES AND GLUCOSE TOLERANCE IN PATIENTS WITH PROLACTINOMA
Authors: PELKONEN RISTO , NIKKILÄ ESKO A. , GRAHNE BERTEL
Published: March 2008

Serum total cholesterol and triglyceride levels were determined in forty‐seven women with prolactinoma and in eighty‐four age‐ and weight‐matched control women. Oral glucose tolerance tests (OGTT) were performed and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were determined in twelve patients before and after transsphenoidal removal of the prolactinoma.

The mean levels of serum cholesterol and triglyceride were significantly higher in patients than in controls. The 90% cut‐off line of controls for serum cholesterol was exceeded by 36% and that for serum triglyceride by 23% of the patients. The triglyceride levels were raised only in patients with GH‐deficiency whereas patients with normal GH secretion had normal triglyceride. Plasma LPL activity was significantly reduced whereas plasma HL activity was in the upper range of normal.

After the removal of prolactinoma the serum prolactin levels decreased in all patients and seven started to menstruate. The oral glucose tolerance was improved and the plasma insulin response decreased. Serum lipid levels and the lipase activities, however, did not change.

Conclusion: prolactinoma is associated with metabolic abnormalities characterized by hyperlipidaemia, low plasma LPL activity and insulin resistance.
EFFECT OF RADIOIODINE ON STIMULATORY ACTIVITY OF GRAVES’IMMUNOGLOBULINS
Authors: ATKINSON S. , McGREGOR A. M. , KENDALL‐TAYLOR PAT , PETERSON M. M. , SMITH B. R.
Published: March 2008

The effects of 131I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves’disease have been studied.

Prior to 131I administration TSAb was detected in 84%, and TBII in 68% of patients. Following 131I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pre treatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity.

These results show that after 131I therapy for Graves’hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement.
GROWTH HORMONE SECRETION AND PLASMA SOMATOMEDIN‐C IN PRIMARY HYPOTHYROIDISM
Authors: CHERNAUSEK S. D. , UNDERWOOD LOUIS E. , UTIGER R. D. , VAN WYK J. J.
Published: March 2008

The effect of thyroid hormone deficiency on plasma immunoreactive somato‐medin‐C concentrations, growth hormone (GH) secretion in response to provocative stimuli, and the plasma somatomedin‐C response to exogenous GH was studied in patients with primary hypothyroidism. Plasma Somatomedin‐C concentrations were below the 95% confidence interval in 11 of 12 hypothyroid patients (mean ± SD=0·27·0±14 U/ml). With thyroid hormone therapy the mean plasma somatomedin‐C level increased four‐fold (1·00·0±43 U/ml). The capacity to secrete GH in response to pharmacological agents was impaired in 3 of the 6 hypothyroid patients tested and normal in the remainder. When the same 6 patients were given a single intramuscular injection of GH (0·1 U/kg) plasma somatomedin‐C concentrations increased four‐fold by 28 h after the injection. The magnitude of the somatomedin‐C response was equal to or greater than that reported for euthyroid GH deficient subjects treated similarly. This study shows that plasma somatomedin‐C concentrations are diminished by hypothyroidism. The decreased somatomedin‐C levels do not appear to result from resistance to the stimulatory effect of GH, but may be either a result of diminished GH secretion or may be due to direct effects of hypothyroidism upon somatomedin production.
EFFECT OF BROMOCRIPTINE IN PITUITARY‐DEPENDENT CUSHING'S SYNDROME
Authors: BOSCARO M. , BENATO M. , MANTERO F.
Published: March 2008

To assess the therapeutic value of a dopaminergic drug on abnormal ACTH secretion, we studied the effect of bromocriptine during short and long‐term treatment in nine patients with active pituitary‐dependent Cushing's syndrome. The single oral dose effect of bromocriptine (2·5 mg at 0800 h) on ACTH samples obtained every half hour for 3 h, was studied in six patients with Cushing's disease; in no case was suppression of ACTH observed. In five patients, the effect of bromocriptine was also investigated after its administration for two consecutive days (5 mg/d) with plasma samples taken every half hour for 12 h; in three cases no suppression of plasma ACTH was observed, while the other two showed a significant decrease. Three of our patients (a nonresponder to the single dose, a responder to the two‐day treatment, and an untested patient) were subjected to prolonged bromocriptine administration (2–45 months). In the first two patients only, biochemical data and clinical symptoms showed improvement, while the other patient showed only initial benefit. These data show that bromocriptine may occasionally reduce ACTH secretion in pituitary‐dependent Cushing's syndrome, and that a single oral dose bromocriptine test fails to identify the patients who will benefit from this treatment.
PERSISTENCE OF MÜLLERIAN DUCTS IN MALE PSEUDOHERMAPHRODITISM, AND ITS RELATIONSHIP TO CRYPTORCHIDISM
Authors: JOSSO NATHALIE , FEKETE CLAIRE , CACHIN OLGA , NEZELOF C. , RAPPAPORT R.
Published: March 2008

Twenty‐two cases of male pseudohermaphroditism with persistence of Müllerian duct derivatives were reviewed. In 12 cases of mixed gonadal dysgenesis and five cases of dysgenetic male pseudohermaphroditism, testosterone‐dependent steps of sex differentiation were also impaired, and testicular dysgenesis was prominent, even in the younger age group. The capacity of testes to inhibit the ipsilateral Müllerian duct was correlated with testicular descent: it is suggested that testicular dysgenesis explains both the functional and topographical testicular abnormalities observed in these male pseudohermaphrodites. Five other patients were cryptorchid but externally normally virilised, persistence of Müllerian derivatives representing their only abnormality of sex differentiation. Testicular structure was usually normal or showed changes attributable to long‐standing cryptorchidism. It is suggested that in these patients, persistence of Müllerian derivatives is due to an inborn error of metabolism, affecting the binding of anti‐Müllerian hormone to its receptor and that failure of testicular descent is caused by mechanical restraint by the abdominal Müllerian organs.
SCINTIGRAPHIC LOCALIZATION OF PHAEOCHROMOCYTOMAS
Authors: FISCHER M. , VETTER W. , WINTERBERG B. , HENGSTMANN J. , ZIDEK W. , FRIEMANN J. , VETTER H.
Published: March 2008

131I‐meta‐iodobenzylguanidine scanning was performed in 14 patients with phaeochromocytomas. In all but one patient scintigraphy successfully localized the lesion(s). The results confirm that scintigraphic imaging with 131I‐meta‐iodobenzylguanidine, a noninvasive method, is a valid and reliable procedure for imaging and localization of adrenal and extra‐adrenal phaeochromocytomas, both benign and malignant.
EFFECT OF PANCREATIC GROWTH HORMONE RELEASING FACTORS ON GH SECRETION BY HUMAN SOMATOTROPHIC PITUITARY TUMOURS IN CELL CULTURE
Authors: ADAMS E. F. , BHUTTACHARJI S. C. , HALLIWELL C. L. J. , LOIZOU M. , BIRCH G. , MASHITER K.
Published: March 2008

Human pancreatic growth hormone releasing factors (hpGRF(1–40) and hpGRF(1–44)) significantly stimulated GH secretion when added to cell cultures of human somatotrophic pituitary tumours for 2 h. There was little difference in potency between the two peptides, and the response of different tumours varied, ranging from 30% to 500% increases in GH secretion over control levels. This stimulatory effect was blocked by somatostatin (SRIF) and bromocriptine. The suppressive effect of bromocriptine, but not of SRIF, was overcome by high doses of hpGRF(1–44). TRH stimulated GH secretion by one of three somatotrophic tumours in cell culture, and it was found to potentiate the stimulatory effects of hpGRF(1–44). These results demonstrate that hpGRFs increase serum GH levels in man by a direct action at the pituitary somatotroph level.
A CASE OF ‘ESSENTIAL’ HYPERNATRAEMIA DUE TO RESETTING OF THE OSMOSTAT
Authors: GILL G. , BAYLIS P. , BURN J.
Published: March 2008

We describe a 24‐year‐old short, obese girl who has bizarre episodic neurological abnormalities related to hyperosmolality due to hypernatraemia. Investigation of osmoregulation by water loading and infusion of hypertonic saline revealed (i) hypodipsia with thirst onset raised to plasma osmolality of 332 mmol/kg and (ii) elevation of the threshold for vasopressin release (plasma osmolality 320 mmol/kg) but normal slope of the plasma vasopressin‐plasma osmolality curve. Baroregulated vasopressin release was also grossly subnormal. Other hypothalamo‐pituitary investigations showed deficiencies of releasing hormones for gonadotrophins and growth hormone, but prolactin response to combined hypoglycaemia and TRH was blunted. She demonstrated other anomalies including hyperlipoproteinaemia and defective lymph drainage of the legs. Skull X‐rays, together with computerized tomography and nuclear magnetic resonance scans of the hypothalamo‐pituitary region and the rest of the brain were normal. We believe that this is the first case of essential hypernatraemia documented with direct evidence of resetting of the osmostat.
OVINE CORTICOTROPHIN RELEASING FACTOR STIMULATES ACTH RELEASE FROM HUMAN CORTICOTROPHINOMA CELLS IN CULTURE; INTERACTION WITH HYDROCORTISONE AND ARGININE VASOPRESSIN
Authors: WHITE M. C. , ADAMS E. F. , LOIZOU MARY , MASHITER K. , FAHLBUSCH R.
Published: March 2008

We have investigated the effects of ovine corticotrophin releasing factor (oCRF) and its interaction with hydrocortisone (HC), and arginine vasopressin (AVP) on ACTH release from human corticotrophinoma cells in culture. Tumour tissue was obtained from six patients (three with active Cushing's disease and three with Nelson's syndrome). Cultures were maintained for periods of up to six months. Ovine CRF (21 nmol) significantly (P>0·01) stimulated ACTH release from all tumours. Dose response (21 pmol‐21 nmol) effects were observed for the three tumours investigated over 2 and 4 h. Cortisol (20 μmol) significantly (P>0·01) inhibited basal ACTH release from one tumour (Nelson's syndrome) by 75% over 4 h, and completely prevented the stimulatory effects of oCRF. AVP directly stimulated ACTH release from two tumours (Nelson's syndrome), and also potentiated the stimulatory action of oCRF during 30 min incubations. These data show corticotrophinoma cells from subjects with Cushing's disease and Nelson's syndrome can be directly stimulated by hypothalamic oCRF and may be potentiated by AVP. Cortisol and oCRF have been shown in one tumour to have antagonistic actions at the pituitary level.
PARATHYROID HORMONE‐LIKE BIOACTIVITY IN TUMOURS FROM PATIENTS WITH ONCOGENIC OSTEOMALACIA
Authors: SESHADRI MANDALAM S. , CORNISH C. J. , MASON R. S. , POSEN S.
Published: March 2008

Extracts from the tumours of three patients with oncogenic osteomalacia stimulated renal adenylate cyclase in a parathyroid hormone (PTH) responsive system. The stimulation was suppressed by a specific PTH antagonist. These observations suggest that osteomalacia‐producing tumours exert some of their effects through PTH‐like material acting on PTH receptors.
EFFECTS OF HIGH‐DOSE AND LOW‐DOSE NALOXONE ON PLASMA ACTH IN PATIENTS WITH ACTH HYPERSECRETION
Authors: DEUSS U. , ALLOLIO B. , KAULEN D. , FISCHER H. , WINKELMANN W.
Published: March 2008

The effect of a high (5–4 mg/h) and a low (0–8 mg/h) dose of naloxone (i.v. over a period of 90 min) on ACTH secretion was compared with placebo in patients with Addison's disease, congenital adrenal hyperplasia, Cushing's disease or Nelson's syndrome. In seven patients with primary adrenal insufficiency the high dose of naloxone provoked a significant increase of plasma ACTH concentrations (P<0.02) whereas the low dose of naloxone failed to influence ACTH secretion. In six patients with ACTH dependent Cushing's disease or Nelson's syndrome both doses failed to alter plasma ACTH levels. These results support the concept of inhibitory δ‐or k‐opiate receptors in the regulation of ACTH secretion. In patients with Cushing's disease or Nelson's syndrome ACTH secretion is insensitive to naloxone, presumably because of an autonomous pituitary adenoma or hypothalamic derangement.
EFFECT OF A SINGLE BOLUS OF ETOMIDATE UPON EIGHT MAJOR CORTICOSTEROID HORMONES AND PLASMA ACTH
Authors: ALLOLIO B. , DÖRR H. , STUTTMANN R. , KNORR D. , ENGELHARDT D. , WINKELMANN W.
Published: March 2008

In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17αOH‐progesterone, 11‐deoxycortisol, cortisol, cortisone, corticosterone, 11‐deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 ± 124 vs. 117 ± 74 pg/ml, mean ± SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P<0.01), cortisone (P<0.01), corticosterone (P<0.01), and aldosterone (P<0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11‐deoxycortisol and 11‐deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 ± 28 nmol/1 and 7.04 ± 0.47 nmol/1, respectively, P<0.01) demonstrating inhibition of 11β‐hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17α‐OH‐progesterone levels was found between the two groups indicating that the cholesterol‐side‐chain cleavage enzyme is less sensitive to etomidate than 11β‐hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid‐synthetic pathway (e.g. cholesterol‐side‐ chain cleavage enzyme) is of little clinical relevance.
THYROTROPHIN BLOCKING ANTIBODIES IN THE SERA OF MOTHERS WITH CONGENITALLY HYPOTHYROID INFANTS
Authors: GINSBERG JODY , WALFISH P. G. , RAFTER D. J. , VON WESTARP C. , EHRLICH R. M.
Published: March 2008

We examined IgG from 15 mothers of infants with congenital hypothyroidism for their ability to block TSH‐stimulated iodine organification in vitro. Only one out of 15 of these IgGs exhibited TSH‐blocking activity. This IgG could inhibit TSH action by 30–50%. It could not block radiolabelled TSH from binding to its receptor but did inhibit dibutyryl cyclic AMP stimulation of iodine organification implying a unique effect on post‐receptor processes via a membrane binding site distant from the TSH binding site. Interestingly, there was no evidence of autoimmune thyroid disease in the mother. These results suggest that the transplacental passage of TSH‐blocking antibodies plays little, if any, role in the development of congenital hypothyroidism.
THE SENSITIVITY OF GROWTH HORMONE AND PROLACTIN SECRETION TO THE SOMATOSTATIN ANALOGUE SMS 201–995 IN PATIENTS WITH PROLACTINOMAS AND ACROMEGALY
Authors: LAMBERTS S. W. J. , ZWEENS M. , KLIJN J. G. M. , VAN VROONHOVEN C. C. J. , STEFANKO S. Z. , DEL POZO E.
Published: March 2008

The somatostatin analogue SMS 201–995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201–995 and whether co‐secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201–995. The S.C. administration of 50 μg SMS 201–995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 μg three times a day also did not affect PRL levels. The single administration of 50 μg SMS 201–995 in 22 acromegalic patients lowered plasma GH levels for 2–6 h to less than 5 μg/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH‐containing tumours and in seven patients there were mixed GH/PRL‐containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201–995 did not differ between the patients with pure GH or mixed GH/PRL‐containing adenomas. Plasma PRL levels were not affected by SMS 201–995 in the patients with pure GH‐secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL‐containing tumour with SMS 201–995 (100 μg three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201–995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL‐containing tumours PRL secretion in some patients is sensitive to SMS 201–995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH‐secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.
TALL STATURE: A CLINICAL, ENDOCRINOLOGICAL AND RADIOLOGICAL STUDY
Authors: HINDMARSH P. C. , STANHOPE R. , KENDALL B.E. , BROOK C. G. D.
Published: March 2008

We have studied GH secretory dynamics in 38 (25 F, 13 M) children referred for investigation and treatment of tall stature (Height SD score (SDS)< 1·8). Five children had elevated basal GH levels (mean 20·4 mU/l) and a further four had abnormal GH responses to exogenous TRH. Two other children had paradoxical GH responses to oral glucose loading. Although one of these was receiving high dose testosterone to limit final height. All these children were pubertal and did not show concordance between peak GH concentration observed after insulin‐induced hypoglycaemia and during stage IV sleep. Twenty‐four hour GH profiles revealed increased GH pulse amplitude and area under the pulse during puberty. Morning GH secretion was also regularly observed and it is possible that the paradoxical responses seen by us and reported by others reflect this increased physiological secretion. Pituitary radiology revealed morphological abnormalities suggestive of microadenomata in 17 patients but these were all in late puberty and these changes may be related more to the effects of sex hormones than to somatotroph pathology. ‘Abnormal’ endocrinology and radiology are seen in tall children in puberty and must be interpreted with caution.
A RE‐EVALUATION OF DOPAMINE EXCRETION IN PHAEOCHROMOCYTOMA
Authors: TIPPETT P. A. , McEWAN A. J. , ACKERY D. M.
Published: March 2008

In a re‐evaluation of the use of dopamine as a prognostic factor in phaeochromocytoma, a series of 34 patients was imaged with iodine‐131‐meta‐iodobenzyl‐guanidine, a radiopharmaceutical specifically localized in chromaffin tumours. Fourteen patients were found to have malignant disease. Increased dopamine excretion was found in 9 (64%) of these patients, including all four with primary intra‐adrenal tumours, and this was associated with a poor prognosis. Of the five patients in the malignant group with normal dopamine excretion on referral, the disease extent was minimal and in four the primary tumour had been resected. Twenty patients appeared to have benign phaeochromocytoma from the imaging results. Of these, 16 were intra‐adrenal and four were extra‐adrenal. In 19 the dopamine excretion was within the control range but in one it was marginally increased. From these observations it would seem that dopamine excretion may be a useful prognostic factor when combined with imaging to determine the extent of the disease.
THE USE OF AN LHRH AGONIST, BUSERELIN, IN THE LONG‐TERM MANAGEMENT OF PREMENSTRUAL SYNDROMES
Authors: BANCROFT J. , BOYLE H. , And P. WARNER , FRASER H. M.
Published: March 2008

Buserelin, an LHRH agonist, was given by nasal spray to 20 women with premenstrual syndrome. In 10 women benefits were such that they continued treatment for periods varying from 5 to 15 months. There were significant improvements in mood and physical symptoms, and side‐effects such as hot flushes were mild. The remaining 10 women were all made worse by the spray and stopped it within 2 months. Ovulation was blocked in all women though six showed evidence of ovulation during the first treatment month, and two women later in treatment. Of the long‐term group, six eventually became amenorrhoeic, and four continued to menstruate. There was a significant improvement in symptoms during treatment in the long‐term group. Physical symptoms continued to be worse before any menstrual bleeding. Mood change lost its relationship to menstruation. The adverse effects in the short‐term group were sometimes severe and it is necessary to identify the characteristics of the woman who are likely to show such reactions before recommending this treatment for more general use.
CIRCULATING BRADYKININ‐LIKE IMMUNOREACTIVITY AND THE PENTAGASTRIN‐INDUCED CARCINOID FLUSH
Authors: BALKS H. J. , CONLON J. M. , CREUTZFELDT W. , STÖCKMANN F.
Published: March 2008

Bradykinin and structurally related peptides are potent vasodilators and a role for these kinins in the aetiology of the carcinoid flush has been proposed. Using an antiserum directed against the COOH‐terminal region of bradykinin in radioimmunoassay, the concentrations of bradykinin‐like immunoreactivity in extracts of peripheral blood were compared in patients with carcinoid syndrome (n = 11) and healthy subjects (n = 6). In the fasted state, the concentrations of bradykinin‐like immunoreactivity in the patients (10 ± 5 ng/l) were not significantly different from the concentrations in healthy subjects (6 ± 3 ng/l). An intravenous injection of pentagastrin (0.6 μg/kg) provoked a flush of differing degrees of severity in all patients. In four patients, the flush was concurrent with large rises (277‐, 26‐, 11‐ and 10‐fold over mean basal values) in bradykinin‐like immunoreactivity that was resolved by high performance liquid chromatography into lysyl‐bradykinin and bradykinin (approximate ratio 1:2). In two patients, small rises in immunoreactivity (2.4‐ and 1.7‐fold) occurred after the flush and in the remaining five patients no rise in bradykinin‐like immunoreactivity was measured. In the healthy subjects, the pentagastrin injection did not provoke a flush and no rises in bradykinin‐like immunoreactivity were observed. The data support earlier results obtained using bioassays that the carcinoid flush in some patients is associated with the appearance in blood of bradykinin‐related peptides. It has been shown, however, that these kinins cannot be the sole causative agent of the flush. It is suggested, therefore, that the aetiology of the flush is probably multi‐factorial.
DEXAMETHASONE‐SUPPRESSIBLEHYPERALDOSTERONISM: STUDIES ON OVERPRODUCTION OF 18‐HYDROXYCORTISOL IN THREE AFFECTED FAMILY MEMBERS
Authors: DAVIS J. R. E. , BURT D. , CORRIE J. E. T. , EDWARDS C. R. W. , SHEPPARD M. C.
Published: March 2008

We report a newly diagnosed family in which a father and his two sons were found to be hypertensive and to have the rare familial condition dexametha‐sone‐suppressible hyperaldosteronism (DSH). All three patients became normotensive on dexamethasone treatment alone and have been successfully maintained on low doses of the drug for 6 months since diagnosis. Each of the patients had extremely high plasma and urinary concentrations of the recently discovered steroid 18‐hydroxycortisol, which were more than ten times higher than the upper normal limit. Plasma levels were readily suppressed by dexamethasone treatment. The hypothesis that 18‐hydroxycortisol might derive from 18‐hydroxylation of recirculating Cortisol was tested by measuring plasma 18‐hydroxycortisol levels during low‐dose and high‐dose hydrocortisone infusions, in a normal subject and in one of the patients with DSH. During the high‐dose infusions (with plasma Cortisol levels of 3000‐5000 nmol/1) there was net production of 18‐hydroxycortisol within 8 h, but this was not observed during the low‐dose infusions (plasma Cortisol levels 300‐400 nmol/1). The origin of 18‐hydroxycortisol remains uncertain: these findings do not support the recirculation theory, but lend weight to the alternative hypothesis that 18‐hydroxycortisol is produced in transitional adrenocortical tissue. This steroid is of considerable value in the differential diagnosis of primary hyperaldosteronism and may also be important as a marker of transitional adrenal cell function.
THE COMBINED USE OF SODIUM VALPROATE AND METYRAPONE IN THE TREATMENT OF CUSHING'S SYNDROME
Authors: NUSSEY S. S. , PRICE P. , JENKINS J. S. , ALTAHER A. R. H. , GILLHAM B. , JONES M. T.
Published: March 2008

We have investigated the combined use of metyrapone and sodium valproate in the treatment of five cases of dexamethasone‐suppressible Cushing's disease and one case with dexamethasone non‐suppressible disease. Metyrapone alone reduced 24 h urinary free cortisol (UFC) and plasma cortisol concentrations. Addition of sodium valproate to metyrapone produced a further reduction in these values in five of six patients with a reduction in plasma ACTH in three of five patients who had dexamethasone‐suppressible disease. Plasma 11‐deoxy‐cortisol increased markedly on metyrapone. However, addition of valproate produced a further rise in 11‐deoxycortisoi values in four of five patients including the patient with dexamethasone non‐suppressible disease. The results suggest that valproate may be a useful addition to metyrapone in the medical treatment of some patients with Cushing's syndrome and that it may have an action both at the hypothalamus and peripherally.
EFFECTS OF LUGOL'S SOLUTION ON THYROID FUNCTION IN NORMALS AND PATIENTS WITH UNTREATED THYROTOXICOSIS
Authors: TAN T. T. , MORAT P. , NG M. L. , KHALID B. A. K.
Published: March 2008

Thirty‐eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo‐pituitary‐thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.