bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing usage‐based e‐journal pricing
Authors: HARWOOD Paul , PRIOR Albert
Published: March 2008

Following the report of a study in 2004 into journals business models, the UK's Joint Information Systems Committee (JISC) decided to arrange to undertake trials of two of the models addressed in the study. The models tested were: ‘Pay‐per‐View Converting to Subscription’ and ‘Core Plus Peripheral'. One of the reasons for the trials was to try to ascertain how the models compared with the Big Deals offered by publishers, but they also aimed to consider the technical, administrative, and commercial issues that might be involved in operating the models in practice. The trials took place during 2006 and involved five publishers and ten UK academic libraries. The models trialled in practice deviated from those addressed in the report of the original study and were based on accesses charged not on a pay‐per‐view basis, but on an agreed charge per full‐text download. Users at the participating libraries had access during the year to all the journals published by the participating publishers. The trials produced a number of useful findings including the need to exclude charging for full‐text downloads that were freely available, implications of usage data from intermediaries, issues of archival access, and budgeting and administrative considerations for both libraries and publishers.
A day in the life of an academic chemist
Authors: JABRI Evelyn
Published: March 2008

A typical day for an academic chemist is a whirlwind of activity, where multitasking and effective time management ensure success. One major focus is securing research grants, and much of that process requires keeping up to date with the scientific literature. Many chemists have established mechanisms to identify and store papers relevant to their research program. Now they are turning to new tools to aggregate, personalize, and share their knowledge.
Hed1 regulates Rad51-mediated recombination via a novel mechanism
Authors: Busygina Valeria , Sehorn Michael G. , Shi Idina Y. , Tsubouchi Hideo , Roeder G. Shirleen , Sung Patrick
Published: March 2008

Two RecA orthologs, Rad51 and Dmc1, mediate homologous recombination in meiotic cells. During budding yeast meiosis, Hed1 coordinates the actions of Rad51 and Dmc1 by down-regulating Rad51 activity. It is thought that Hed1-dependent attenuation of Rad51 facilitates formation of crossovers that are necessary for the correct segregation of chromosomes at the first meiotic division. We purified Hed1 in order to elucidate its mechanism of action. Hed1 binds Rad51 with high affinity and specificity. We show that Hed1 does not adversely affect assembly of the Rad51 presynaptic filament, but it specifically prohibits interaction of Rad51 with Rad54, a Swi2/Snf2-like factor that is indispensable for Rad51-mediated recombination. In congruence with the biochemical results, Hed1 prevents the recruitment of Rad54 to a site-specific DNA double-strand break in vivo but has no effect on the recruitment of Rad51. These findings shed light on the function of Hed1 and, importantly, unveil a novel mechanism for the regulation of homologous recombination.
Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma
Authors: Briggs Kimberly J. , Corcoran-Schwartz Ian M. , Zhang Wei , Harcke Thomas , Devereux Wendy L. , Baylin Stephen B. , Eberhart Charles G. , Watkins D. Neil
Published: March 2008

Medulloblastoma is an embryonal tumor thought to arise from the granule cell precursors (GCPs) of the cerebellum. PATCHED (PTCH), an inhibitor of Hedgehog signaling, is the best-characterized tumor suppressor in medulloblastoma. However, <20% of medulloblastomas have mutations in PTCH. In the search for other tumor suppressors, interest has focused on the deletion events at the 17p13.3 locus, the most common genetic defect in medulloblastoma. This chromosomal region contains HYPERMETHYLATED IN CANCER 1 (HIC1), a transcriptional repressor that is a frequent target of epigenetic gene silencing in medulloblastoma. Here we use a mouse model of Ptch1 heterozygosity to reveal a critical tumor suppressor function for Hic1 in medulloblastoma. When compared with Ptch1 heterozygous mutants, compound Ptch1/Hic1 heterozygotes display a fourfold increased incidence of medulloblastoma. We show that Hic1 is a direct transcriptional repressor of Atonal Homolog 1 (Atoh1), a proneural transcription factor essential for cerebellar development, and show that ATOH1 expression is required for human medulloblastoma cell growth in vitro. Given that Atoh1 is also a putative target of Hh signaling, we conclude that the Hic1 and Ptch1 tumor suppressors cooperate to silence Atoh1 expression during a critical phase in GCP differentiation in which malignant transformation may lead to medulloblastoma.
ACTH SECRETION BY BRONCHIAL CARCINOID TUMOURS
Authors: MASON A. M. S. , RATCLIFFE J. G. , BUCKLE R. M. , MASON A. STUART
Published: March 2008

Seven cases of adrenocortical hyperfunction associated with ACTH secreting carcinoid tumours of lung are reported. The clinical manifestations, laboratory investigations and treatment are compared with twenty‐one similar cases already recorded. The clinical picture of this disorder shows features of both pituitary dependent Cushing's syndrome and of the ectopic ACTH syndrome associated with carcinoma of lung. The problems of accurate diagnosis are described. The effects of treatment, both surgical and medical, of the adrenocortical hyperfunction are described and the problems of identifying and removing the carcinoid tumour are discussed.
EFFECTS OF ARTIFICIAL MENOPAUSE ON PLASMA AND URINE CALCIUM AND PHOSPHATE
Authors: GALLAGHER J. C. , YOUNG M. M. , NORDIN B. E. C.
Published: March 2008

Plasma and urine calcium and phosphate were determined in nine patients before and after oophorectomy and in eleven patients before and after simple hysterectomy. Oophorectomy was followed by a significant rise in the mean plasma and fasting urine calcium, and a mean rise of 37 mg in the 24 hr calcium which, however, was not significant. Hysterectomy alone caused no significant change in plasma or urine calcium. In both groups only small changes were observed in plasma and urine phosphate and these did not reach the level of significance. The mean urine hydroxyproline/creatinine ratio rose significantly in six patients after oophorectomy but did not change after hysterectomy. It is suggested the rise in plasma and urine calcium following oophorectomy is due to increased bone resorption which does not occur after simple hysterectomy.
GONADOTROPHIN TEST OF THE FUNCTIONAL CAPACITY OF LEYDIG CELLS IN NORMAL AND HYPOGONADAL BOYS
Authors: PERHEENTUPA J. , DESSYPRIS A. , ADLERCREUTZ H.
Published: March 2008

A human chorionic gonadotrophin stimulation test of prepubertal testes was studied at two different dosage levels. Three doses of 500 i.u. or 1500 i.u. were administered intramuscularly at 2‐day intervals, and the plasma testosterone concentration was measured with a competitive protein‐binding technique before the stimulation and 24 hr after the last dose.

The test was carried out with the smaller dose in fourteen and with the larger dose in eighteen boys with two clinically normal testes. Ten boys with male pseudo‐hermaphroditism, four with bilateral cryptorchidism, two with the Prader‐Labhart‐Willi syndrome, and one with Noonan's syndrome were also tested.

The results, as evaluated in conjunction with the information available in the literature, indicate that appropriate stimulation is obtained with three doses of 1500 i.u. given at 2‐day intervals. Giving the testes enough time to respond is as important as the dose of gonadotrophin. Measurement of the basal concentration of testosterone is of little value. No virilization was observed after this stimulation. The clinical value of the test was clearly indicated by the results obtained in the pathological series.
SECRETION OF PARATHYROID HORMONE IN PRIMARY HYPERPARATHYROIDISM
Authors: O'RIORDAN J. L. H. , WATSON L. , WOODHEAD J. S.
Published: March 2008

Circulating parathyroid hormone was assayed in sixty‐nine patients with primary hyperparathyroidism. The patients were divided into two groups, those with radiological evidence of osteitis fibrosa (twenty patients) and those without such evidence. In this latter group the mean concentration of circulating parathyroid hormone was higher than the mean in a group of normal subjects, but there was great overlap with the normal range, limiting the diagnostic value of the assay in such cases. Much higher concentrations were found in the patients with osteitis fibrosa: all nine patients with concentrations of parathyroid hormone above 3 ng/ml had osteitis fibrosa.
THE Ig CLASS AND LIGHT CHAIN TYPE OF THE LONG ACTING THYROID STIMULATOR
Authors: MAISEY M. N.
Published: March 2008

The Ig class and light chain type of LATS has been examined. Serum samples containing high levels of LATS were assayed before and after incubation with specific antisera to IgG, IgA and IgM, and kappa and lambda light chains. It was found that LATS activity was restricted to the IgG class of immunoglobulins and that the LATS activity was distributed approximately equally between the kappa and lambda type of IgG. These results are consistent with a polyclonal origin for LATS.
MEASUREMENT OF PROGESTERONE IN HUMAN PLASMA
Authors: HORTH C. E. , PALMER R. F.
Published: March 2008

A rapid protein‐binding technique is described for routine plasma progesterone measurements.

Chick plasma is the source of binding‐protein and 3H‐progesterone is the radioligand. Accuracy is ensured by including a recovery determination with each specimen.

In fifteen normal female volunteers, low plasma progesterone values‐0.65 ng/ml ± 0.82 (SD)‐were recorded during the follicular phase of the menstrual cycles, rising 10‐14 days before menstruation to peak levels of 9–17 ng/ml during the luteal phase and then falling abruptly towards the end of the cycle.
A SENSITIVE BIOASSAY FOR ADRENOCORTICOTROPHIC HORMONE IN HUMAN PLASMA
Authors: CHAYEN J. , LOVERIDGE N. , DALY J. R.
Published: March 2008

A technique for the bioassay of adrenocorticotrophic hormone (ACTH) in human plasma is described, and its experimental validation discussed.

Segments of guinea‐pig adrenal are maintained individually for 5 hr in nonproliferative organ culture in a medium reinforced with 10‐3m sodium ascorbate. At the end of this time each segment is exposed to either standard or unknown ACTH for 3 min. The segments are then rapidly chilled to ‐ 70oC and sections cut in a cryostat. The sections are stained by the ferric ferrocyanide technique for reducing groups, and the degree of staining in the zona reticularis measured by scanning and integrating micro‐densitometry. There is an inverse linear correlation between the intensity of the stain and the logarithmic concentration of ACTH over the concentration 0.0025‐2.5 pg/ml of culture medium.

The assay is precise (λ= 0.09) and extremely sensitive. Concentrations of ACTH down to 1 pg/ml may be determined on as little as 0.1 ml of plasma without extraction. Results obtained are in a range similar to that given by the Lipscomb‐Nelson bioassay and by radioimmunoassay.
SKIN COLLAGEN AND THICKNESS IN HYPERTHYROIDISM AND MYXOEDEMA
Authors: BLACK M. M. , BOTTOMS EVA , SHUSTER SAM
Published: March 2008

Skin thickness, collagen content and density have been measured in patients with thyrotoxicosis and myxoedema. In hyperthyroidism the skin was of normal thickness but the absolute collagen content and density of collagen were both increased as was the percentage collagen content. In myxoedema both absolute percentage collagen content and density remained normal but the skin thickness was significantly increased and this correlated well with the severity of hypothyroidism and response to treatment.
PORCINE CALCITONIN AS A RENAL VASODILATOR IN MAN
Authors: EDWARDS I. R. , SMITH A. J.
Published: March 2008

Porcine calcitonin in intravenous doses of 1, 5, 10 and 20 MRC units produced acute increases in urinary volume and sodium, potassium, chloride and bicarbonate excretion in four normal subjects.

Infusion of 10 MRC units over a 30 min period in six normal men produced significant increases in urinary volume and sodium, calcium, magnesium, chloride and urea excretion. Urinary potassium, phosphate and bicarbonate were also increased but the increases were not significantly different from control values.

These changes in urinary composition accompanied a significant increase in effective renal plasma flow (para‐amino hippurate clearance) and a smaller increase in inulin clearance.

It is suggested that porcine calcitonin acts as a renal vasodilator in man and that changes in renal electrolyte excretion occur as a consequence. It is possible that renal vasodilation is effected by an active intermediary released by calcitonin rather than by the hormone itself.
COMPARISON OF ANXIETY IN THYROTOXIC AND NEUROTIC PATIENTS USING SKIN CONDUCTANCE MEASUREMENTS
Authors: MORAKINYO V. O. , AITKEN R. C. B. , ZEALLEY A. K. , IRVINE W. J.
Published: March 2008

The experiment reported in this paper was designed to examine the belief that the mood state (anxiety) associated with thyrotoxicosis was phenomenologically similar to the anxiety occurring in functional (neurotic) states. For this purpose a psychophysiological technique was used which has been shown to be reliable and objective in the differentiation of neurotically anxious patients. It was shown that, unlike the situation in patients with neurotic anxiety states, the psychogalvanic reflex of patients with thyrotoxicosis habituated to a repeated standard stimulus and an initially high rate of spontaneous fluctuations soon settled.

The abnormality detected in the thyrotoxic patients consisted of increased reactivity or responsivity and hyperarousal. Although patients with neurotic anxiety states are chronically hyperaroused, the relation of this hyperarousal to the mode of habituation of their psychogalvanic reflex differs from that found for thyrotoxic patients. It seems, therefore, most unlikely that the hyperarousal associated with thyrotoxicosis shares a common origin and mechanism with the hyperarousal occurring in functional (neurotic) anxiety states.
The effect of surgical operation of moderate severity on thyroid function
Authors: KIRBY R. , CLARK And F. , JOHNSTON IVAN D. A.
Published: March 2008

The effect of surgery on thyroid hormone transport was studied in ten subjects undergoing vagotomy and pyloroplasty for chronic duodenal ulceration. Measurements of the serum protein bound iodine (PBI), thyrotrophic hormone (TSH), T4 binding capacities of the thyroxine binding proteins (TBPA and TBG), percentage and absolute free thyroxine (T4) and percentage free triiodothyronine (T3) were made before and after operation. Operation produced a sharp reduction in the maximal binding capacity of TBPA with no apparent change in TBG. There were significant increases in percentage and absolute free T4 and in percentage free T3. There was no change in PBI and no increase was demonstrated in TSH after operation. The changes appeared to be unrelated to the increase in adrenocortical hormones associated with injury. It is suggested that thyroid hormones may have an important role in post‐injury metabolism.
PARTIAL AND TOTAL LIPODYSTROPHY: CHANGES IN CIRCULATING SUGAR, FREE FATTY ACIDS, INSULIN AND GROWTH HORMONE FOLLOWING THE ADMINISTRATION OF GLUCOSE AND OF INSULIN
Authors: BOUCHER B. J. , COHEN R. D. , FRANKEL* R. J. , STUART MASON A. , BROADLEY G.
Published: March 2008

The effect of glucose or insulin administration in a group of five patients with partial lipodystrophy and three with total lipodystrophy was studied. In only one patient was the glucose tolerance curve abnormal. Mean fasting serum insulin, growth hormone, free fatty acids (FFA) and triglycerides were all significantly elevated. The serum insulin response to glucose was grossly elevated. Insulin resistance was present. The serum insulin was shown to be immunologically normal, Exogenous insulin disappeared at a normal rate from the circulation, suggesting that the elevated insulin levels in the fasting state and after glucose were due to hypersecretion. Serum growth hormone levels failed to suppress normally after glucose. Serum FFA fell after glucose or insulin administration. In one patient treated with propranolol unusual insulin responses to the administration of glucose were observed. A working hypothesis capable of explaining the metabolic changes in lipodystrophy is proposed.
AN ASSESSMENT OF PLASMA TSH RADIOIMMUNOASSAY AND OF THE TSH STIMULATION TEST IN THE DIAGNOSIS OF 100 CONSECUTIVE PATIENTS WITH SUSPECTED HYPOTHYROIDISM
Authors: IRVINE W. J. , TOFT A. D. , HUNTER W. M. , KIRKHAM K. E.
Published: March 2008

A plasma TSH estimation and a TSH stimulation test were performed on each of 100 consecutive patients seen at a thyroid clinic in whom it was necessary to exclude a diagnosis of hypothyroidism. None of the patients had received replacement therapy. The normal response to 10 i.u. bovine TSH administered intramuscularly on three consecutive days was shown to be an absolute increment in the 4 hr uptake of 132I by the thyroid gland of at least 13%. The mean plasma TSH in twenty‐five untreated euthyroid patients, who had neither goitres nor thyroid antibodies, whose TSH stimulation tests were normal and in whom there was no evidence of hypopituitarism, was 3.8 μU/ml+3.6 (2 S.D.). All forty‐nine patients with primary hypothyroidism had plasma TSH levels in excess of 25 μU/ml. In eighty‐nine of the 100 patients, the radioimmunoassay of plasma TSH and the TSH stimulation test gave similar information about the reserve of thyroid function and in five euthyroid patients the plasma TSH was > 7.4 μU/ml while the TSH stimulation test was normal. The remaining six subjects (including one patient with hypopituitarism and three who had been treated with radioiodine for thyrotoxicosis) were euthyroid with an abnormal TSH stimulation test and a plasma TSH of <7.4 μU ml.

For clinical purposes a plasma TSH of <7.4 μU/ml indicates a normal reserve of thyroid function, a plasma TSH between 7.4 and 25 μU/ml is equivocal, and a plasma TSH >25 μU/ml indicates an impaired or absent reserve of thyroid function with or without hypothyroidism. It is concluded that a single plasma TSH estimation should replace the time‐consuming TSH stimulation test in the assessment of thyroid reserve.
Plasma Unconjugated and conjugated 17‐hydroxycorticosteroids in different clinical disorders
Authors: PAL S. B.
Published: March 2008

A procedure was developped for the estimation of plasma unconjugated and conjugated 17‐hydroxycorticosteroids as 17‐oxogenic steroids. The reliabiligy criteria of the method were assessed. In 100 normal individuals, aged between 15 and 65 years, the average concentrations of junconjugated 17‐hydrosycorticosteroids were 12 ug/100 ml (range 10‐32) and of conjugated 17‐hydroxycorticosterods were 12 ug/100 ml (range 10‐32) and of conjugated 17‐hydroxycorticosteroids 16 ug/100 ml (range 15‐52). When an adrenal stimulation test was performed, the concnetrations of these two groups of steroids showeed a twofold increase after the administration of ACTH and the concentrations decreased after an adrenal suppression test with dexamethasone. Patients with rheumatoid arthiritis not previously treated with steroids or ACTH, Cushing's syndrome, carcinoma, were studied. The results showed that the determination of plasma unconjugated and conjugated corticosteroids in these patients is clinically more meaningful than the estimation of plasma cortisol alone.
Enhanced plasma thyrotrophin response to thyrotrophin‐releasing hormone following oestradiol administration in man
Authors: FAGLIA G. , BECK‐PECCOZ P. , FERRARI C. , AMBROSI B. , SPADA ANNA , TRAVAGLINI P.
Published: March 2008

The plasma TSH response to 100 μg of TRH i.v. was studied in six normal women and in seven men before and after the administration of 10.0 mg of oestradiol valerate for 5 consecutive days. Before oestrogen treatment the females appeared more responsive than males. After treatment the response remained unchanged in females while appearing enhanced in males. Oestrogen treatment did not modify either the basal plasma TSH concentration or the serum thyroxine, the labelled tri‐iodothyronine uptake and the calculated free thyroxine index. It is concluded that oestrogens play a role in modulating the secretion of TSH from the human pituitary.
ANTIDIURETIC EFFECT OF CLOFIBRATE AND CARBAMAZEPINE IN DIABETES INSIPIDUS: STUDIES ON FREE WATER CLEARANCE AND RESPONSE TO A WATER LOAD
Authors: BONNICI FRANÇOIS
Published: March 2008

Studies of the antidiuretic effect of clofibrate and carbamazepine were undertaken in five patients with vasopressin‐sensitive diabetes insipidus and in two siblings with hereditary vasopressin‐resistant diabetes insipidus. Four out of the five vasopressin‐sensitive patients responded with a marked fall in urine output, an increase in urine osmolality, a decrease in plasma osmolality, and produced a negative free water clearance. No effect was demonstrable in one patient who presumably had a total deficit in vasopressin, and in the two siblings with vasopressin resistance. In contrast to the results obtained on chlorpropamide, the ability to excrete a water load on therapy was retained, implying that a physiological stimulus is still capable of inhibiting the small secretion of vasopressin when on therapy.

The findings suggest that clofibrate and carbamazepine act by stimulating vasopressin release from the neurohypophysis and may be preferable to chlorpropamide in patients with partial diabetes insipidus.
THE EFFECT OF THYROTROPHIN‐RELEASING HORMONE ON PLASMA PROLACTIN AND THYROTROPHIN LEVELS IN PRIMARY HYPOTHYROIDISM
Authors: TOFT A. D. , BOYNS A. R. , COLE E. N. , GROOM G. V. , HUNTER W. M. , IRVINE W. J.
Published: March 2008

Plasma prolactin and thyrotrophin (TSH) were measured by radioimmunoassay before, at 20 min and 60 min after the intravenous administration of 200 μg thyrotrophin‐releasing hormone (TRH) in thirty‐two patients with untreated primary hypothyroidism and in sixteen normal volunteers. Whereas basal plasma TSH was markedly elevated in all the patients with hypothyroidism, a slight, but significant increase (P<0.05) in basal plasma prolactin in primary hypothyroidism could only be demonstrated by matching for age, sex and circulating gonadotrophin levels, ten patients with hypothyroidism with ten normal volunteers. There was, however, no significant difference between the two groups, matched or unmatched, in the plasma prolactin levels, in contrast to the plasma TSH levels, following TRH administration. No apparent relationship was found between basal prolactin and follicle‐stimulating hormone (FSH), luteinizing hormone (LH) or TSH.

Assuming the release of prolactin by TRH to be of physiological significance, the results suggest that TRH secretion by the hypothalamus may be increased in untreated hypothyroidism and that low levels of circulating thyroid hormone increase the sensitivity of the pituitary thyrotrophs, but not the prolactin secreting cells, to TRH. Markedly elevated plasma prolactin levels associated with galactorrhoea were not seen in primary hypothyroidism in the absence of the puerperium or oestrogen therapy.
ACTH, GLUCAGON AND GASTRIN PRODUCTION BY A PANCREATIC ISLET CELL CARCINOMA AND ITS TREATMENT
Authors: BELCHETZ P. E. , BROWN C. L. , MAKIN H. L. J. , TRAFFORD D. J. H. , MASON A. STUART , BLOOM S. R. , RATCLIFFE J. G.
Published: March 2008

The production of ACTH, gastrin and glucagon by a pancreatic islet cell tumour is reported. The tumour contained at least two distinct cell types on electron microscopy. The fulminating hypercorticism was efficiently controlled with metyrapone and aminoglutethimide, but streptozotocin was not an effective anti‐tumour agent.
INTERACTION BETWEEN SECRETION OF THE GONADOTROPHINS, PROLACTIN, GROWTH HORMONE, THYROTROPHIN AND CORTICOSTEROIDS IN MAN: THE EFFECTS OF LH/FSH‐RH, TRH AND HYPOGLYCAEMIA ALONE AND IN COMBINATION
Authors: MORTIMER C. H. , BESSER G. M. , McNEILLY A. S. , TUNBRIDGE W. M. G. , GOMEZ‐PAN A. , HALL R.
Published: March 2008

The interaction between the mechanisms involved in the LH, FSH, growth hormone, prolactin, ACTH and TSH responses to the synthetic LH and FSH releasing hormone, thyrotrophin releasing hormone and insulin induced hypoglycaemia was studied in twelve normal male volunteers. Each subject acted as his own control and the test procedures were performed individually and in combination. The simultaneous administration of one releasing hormone with another or with insulin in no way modified the hormonal responses to either releasing hormone or to hypoglycaemia. Clinical testing with these procedures may therefore be performed simultaneously, so that the pituitary reserve for the five anterior pituitary hormones may be assessed together in under 2 hr. In addition it has been shown that TRH releases a small amount of FSH but not LH in male subjects.
THYROID FUNCTION IN THE NEONATE
Authors: CHAN VIVIAN , SMITH MARGUERITE , HALE P. J. , LANDON J.
Published: March 2008

Urinary thyroxine and triiodothyronine levels, when corrected for creatinine excretions, were significantly elevated in 5‐day‐old infants as compared with levels in normal adults and women during the third trimester of pregnancy. This was consistent with the finding that their free thyroxine index was increased and suggests that the circulating levels of free thyroid hormones are raised in early infancy. Circulating levels of thyroid‐stimulating hormone were not significantly different at 6 days as compared with adult values.
EFFECT OF l‐DOPA ON THE SECRETION OF PLASMA GROWTH HORMONE IN CHILDREN AND ADOLESCENTS
Authors: LARON Z. , JOSEFSBERG Z. , DORON M.
Published: March 2008

The stimulation of growth hormone release in children by L‐dopa has been studied. An oral dose of 0.5 g L‐dopa was administered to fourteen children with, and to fifteen children without, hypothalamic‐pituitary insufficiency. In the control group, L‐dopa induced a release of pituitary growth hormone, the peak of which occurred from 30 to 60 min after ingestion. Nine out of fifteen control subjects showed peak levels of plasma growth hormone greater than 8 ng/ml. None of the patients with hypothalamic‐pituitary insufficiency showed levels greater than 5 ng/ml. In five out of six children with measurable amounts of plasma HGH, and in fourteen children with a lack of HGH, there was a good correlation between the HGH response after L‐dopa, insulin hypoglycaemia and arginine infusion. It is concluded that the administration of one oral dose of L‐dopa can be used as a provocative test of growth hormone secretion.
THE EFFECT OF BLOOD LEUCOCYTES FROM PATIENTS WITH HASHIMOTO'S DISEASE ON HUMAN THYROID CELLS IN MONOLAYER CULTURE
Authors: ROW ERIC LARYEA. VAS V. , VOLPE ROBERT
Published: March 2008

Peripheral blood leucocytes from healthy subjects (control leucocytes) and from patients with Hashimoto's thyroiditis or idiopathic myxoedema, were incubated with 2‐3‐day‐old human thyroid cells in monolayer cultures. After 5‐6 days the Hashimoto leucocytes appeared to induce more thyroid cell destruction than control leucocytes. Thyroid cell function (measured by cell to medium (C/M) ratios of 131I) was reduced in cultures incubated with Hashimoto leucocytes, compared to those incubated with control leucocytes. This effect was not mediated by liberation of thyroid antibodies into the medium, but rather from a direct leucocyte/thyroid cell interaction with a resultant liberation of lysozymes. Preliminary observations indicated that the effect of the Hashimoto leucocytes on thyroid cells could be prevented by prior incubation of the former with anti‐thymocyte globulin; this suggested that sensitized lymphocytes may be directly responsible for the thyroid tissue injury of Hashimoto's disease, perhaps with the adjunctive cooperation of the non‐specific macrophages. Leucocytes from patients with idiopathic myxoedema (with low or absent circulating thyroid antibodies) did not have any effect on the thyroid cells, perhaps because the concentration of peripheral sensitized lymphocytes may possibly have declined in these patients.
SEQUENTIAL ASSESSMENT DURING DRUG TREATMENT OF THYROTOXICOSIS
Authors: ALEXANDER W. D. , McLARTY D. G. , HORTON P. , PHARMAKIOTIS A. D.
Published: March 2008

The course of thyrotoxicosis treated with antithyroid drugs has been studied in detail in 105 thyrotoxic patients. Each patient was seen at intervals of 1–3 months over a period of more than 4 years and thus an average of thirty serial tests of thyroid function were made on each patient. Forty‐three patients remitted after one course of antithyroid drugs. In another forty‐three patients the disease either required operative treatment or was still active 4 years after the start of therapy. The remaining nineteen patients fell into an intermediate group.

In the light of the variable course of the disease, we conclude that most patients with Graves' disease under 45 years are best treated initially with antithyroid drugs. Reassessment of thyroid function at 6‐monthly intervals during and for a period after antithyroid drug therapy is useful and permits selection of the most appropriate method of treatment.
STUDIES OF THYROID FUNCTION USING 99Tcm IN THYROTOXIC PATIENTS DURING TREATMENT WITH ANTITHYROID DRUGS
Authors: GOOLDEN A. W. G. , WILLIAMS E. D. , THALASSINOS N. C.
Published: March 2008

Serial measurements of 99Tcm uptake have been made in thirty thyrotoxic patients treated with carbimazole and L‐triiodothyronine. All patients were followed up for a minimum period of 1 year at which time eighteen patients were still in remission and twelve had relapsed.

Four of the twenty‐one patients who had a normal 99Tcm uptake at the time treatment was discontinued relapsed within 6 months. Only one of the nine patients whose uptake at the end of treatment was above normal achieved a remission. Changes in 99Tcm uptake during the first 6 months of treatment were less informative and proved to be of limited value in predicting the outcome of treatment.

In the whole group of patients 99Tcm uptake fell during the first 6 months by about 40%, this change being highly significant. The decline in thyroid activity coincided with the time at which treatment was started. It is suggested that treatment with an antithyroid drug may modify the course of the disease.
ANDROGEN METABOLISM IN GYNAECOMASTIC BREAST TISSUE
Authors: MILLER W. R. , McDONALD D. , MacFADYEN I. , ROBERTS M. M. , FORREST A. P. M.
Published: March 2008

The metabolism of [7α‐3H]dehydroepiandrosterone and [4‐14C]testosterone by gynaecomastic breast tissue has been investigated and compared with that in female breast tissue. No conversion of dehydroepiandrosterone to testosterone or testosterone to 5α‐androstandiol was detected in gynaecomastic tissue in contrast to female breast tisue in which such conversions were demonstrable. This suggests that 3β hydroxysteroid dehydrogenase activity is absent in gynaecomastic tissue. The relevance of this deficiency is discussed.
BIOCHEMICAL AND CLINICAL OBSERVATIONS IN A PREGNANCY WITH PLACENTAL SULPHATASE AND OTHER ENZYME DEFICIENCIES
Authors: OAKEY R. E. , CAWOOD MARION L. , MACDONALD R. R.
Published: March 2008

The oestrogen excretion of a pregnant woman, subsequently shown to have placental sulphatase deficiency, was only 1‐2 mg/24 hr, whereas pregnanediol and 17‐oxogenic steroid excretion were within the normal ranges. Plasma concentrations of oestradiol‐17β, progesterone, 17α‐hydroxyprogesterone, 11β‐hydroxycortico‐steroids and corticosteroid‐binding globulin were subnormal. Placental sulphatase activity in vitro towards the sulphates of DHA, pregnenolone and oestrone was negligible, although extracts of a normal placenta showed high activity under identical conditions. The activities of placental enzymes concerned with metabolism of non‐conjugated steroids (3β‐hydroxysteroid dehydrogenase‐isomerase for DHA and for pregnenolone, aromatase complex and 17β‐hydroxysteroid for oestradiol‐17β) were less than those of a normal placenta but were not diminished as severely as sulphatase activity.

Satisfactory uterine contractions were achieved during infusion of prostaglandin E2 or Syntocinon but the cervix failed to dilate. A healthy male infant (3330 g) was delivered at term by Caesarean section.

From the evidence obtained during the study of this patient it appears that (i) the presence of appropriate non‐conjugated substrates may be required for the induction of placental enzymes concerned with the metabolism of free steroids; (ii) measurement of maternal 17‐oxogenic steroid excretion may help to distinguish patients with placental sulphatase deficiency from those whose fetus has adrenal hypoplasia; (iii) further investigations, possibly involving steroid replacement therapy, are required to identify which, if any, of the alterations in plasma steroid concentrations are associated with the failure to achieve cervical dilatation.
ECTOPIC HORMONE PRODUCTION BY NON‐ENDOCRINE TUMOURS
Authors: REES LESLEY H. , RATCLIFFE J. G.
Published: March 2008

The recognition that certain clinical syndromes are due to secretion of hormones by ‘non endocrine’ tumours, has been among the major developments in endocrinology in the last decade and has forged a new link with oncology. The phenomenon has general clinical and biochemical implications. Clinicians now recognize that the accompanying metabolic derangements may be more malign than the neoplams itself, may significantly affect prognosis, and they use the measurement of plasma hormone levels and related substances for diagnosis and management. From the biochemical point of view, the study of ectopic hormone secretion provides new insight into the state of tissue differentiation. It serves as an excellent model for the broader field of inappropriate tumour products, since the structure of most hormones is known and because recent technical advances have improved methods for their purification and assay.
PROLACTIN, TSH, LH AND FSH RESPONSES TO A COMBINED LHRH/TRH TEST AT DIFFERENT STAGES OF THE MENSTRUAL CYCLE
Authors: McNEILLY A. S. , HAGEN C.
Published: March 2008

A combined test with LHRH and TRH was investigated in the normal female subject during the menstrual cycle. LH and FSH responses were not affected by raised prolactin or TSH levels after TRH.

No correlation was seen between either basal levels or responses of prolactin and TSH after TRH, and no difference in responses on days 4 or 24 were observed. The increments in prolactin and TSH were significantly greater in female than in male subjects.

Although FSH responses to LHRH+TRH were not significantly different, LH responses on day 24 were greater than on day 4. A significant linear correlation between FSH and LH responses to LHRH was seen.

The results indicate that prolactin and TSH responses to TRH are greater in female than male subjects and that changes in LH and FSH after LHRH do affect these responses. Normal ranges for hormone responses after LHRH and TRH are defined.
RADIOIMMUNOASSAY OF SERUM LUTEINIZING HORMONE RELEASING HORMONE (LH‐RH) AFTER INTRA‐NASAL ADMINISTRATION AND EVALUATION OF THE PITUITARY GONADOTROPHIC RESPONSE
Authors: BOURGUIGNON JEAN PIERRE , BURGER HENRY G. , FRANCHIMONT PAUL
Published: March 2008

Serum levels of LH‐RH, LH and FSH were measured by radioimmunoassay at frequent intervals in four young men following the intranasal administration of 2 mg synthetic LH‐RH. The initial rise in serum LH‐RH was seen at 2.5 min and the peak was reached at 15 min. There was a rapid response in serum LH, the peak occurring between 30 and 45 min, while FSH levels did not change significantly. It was calculated that 1.25% of the dose was absorbed. The intranasal administration of LH‐RH appears to have considerable therapeutic potential.
SPECIFIC INHIBITION BY SOMATOSTATIN OF GROWTH HORMONE RELEASE AFTER HYPOGLYCAEMIA IN NORMAL MAN
Authors: COPINSCHI G. , VIRASORO E. , VANHAELST L. , LECLERCQ R. , GOLSTEIN J. , L'HERMITE M.
Published: March 2008

In normal man, synthetic linear somatostatin (growth hormone‐release inhibiting hormone) inhibits the growth hormone response to insulin induced hypoglycaemia, but has no influence on plasma levels of cortisol, prolactin, TSH and FSH.
3H‐OESTRADIOL UPTAKE IN VIVO BY HUMAN UTERINE ENDOMETRIUM: EFFECT OF TAMOXIFEN (I.C.I. 46,474)
Authors: LUNAN C. B. , GREEN B.
Published: March 2008

3H‐oestradiol was injected subcutaneously into patients 2 hr prior to hysterectomy. The amount of labelled hormone present at operation in fractions of uterine endometrium and in other tissues was measured.

Patients pretreated with tamoxifen (I.C.I. 46,474) had lower levels of 3H‐oestradiol in the nuclei of the uterine endometrium and of total labelled material in the myometrium than did untreated patients.

In vitro, tamoxifen also inhibited the uptake of 3H‐oestradiol into the nuclei of human uterine endometrium during tissue incubations and its binding to the cytosol receptors.

Fibroids also showed active oestradiol uptake in vivo.
THE RADIOIMMUNOASSAY OF THYROXINE IN UNEXTRACTED HUMAN SERUM
Authors: RATCLIFFE W. A. , RATCLIFFE J. G. , McBRIDE A. D. , HARLAND W. A. , RANDALL T. W.
Published: March 2008

A specific, accurate, precise and simple radioimmunoassay for thyroxine (T4) in small volumes of unextracted serum is described. It discriminates well between levels found in different states of thyroid function. Levels in euthyroid subjects range between 4.3 and 11.2 μg/100 ml (mean 7.7); in untreated hyperthyroid subjects, 13.2‐25.6 μg/100 ml (mean 19.2); and in untreated hypothyroid subjects undetectable to 2.6 μg/100 ml (mean 1.4). There is satisfactory correlation with competitive protein binding and protein bound iodine methods. Because of its advantages over previous techniques, it is suggested that T4 radioimmunoassay will become the routine method of assessing thyroid status.

The measurement of serum thyroxine (T4) is the single most important test in the routine laboratory assessment of thyroid status. Ideally the T4 assay should be specific, cheap, simple and have a high sample capacity. Thyroxine is determined most commonly in serum extracts by competitive protein binding (CPB) methods (Murphy & Pattee, 1964; Ekins et al., 1969) or, indirectly, by estimation of serum protein bound iodine (PBI). Both techniques require the processing of relatively large volumes of serum before assay. The PBI method has the added disadvantage of measuring iodine‐containing compounds other than thyroxine (Acland, 1971).

We report here a specific, precise and simple radioimmunoassay for thyroxine in unextracted human serum and its application to the assessment of thyroid status. It has significant advantages over CPB, PBI and previous radioimmunoassay methods.
RADIOIMMUNOASSAY OF PLASMA TESTOSTERONE
Authors: FORTI G. , PAZZAGLI M. , CALABRESI E. , FIORELLI G. , SERIO M.
Published: March 2008

A radioimmunoassay for the determination of testosterone in human plasma is described. After extraction from plasma, testosterone is separated by paper chromatography. The radioimmunoassay is performed using an antiserum to testosterone‐3‐oxime‐rabbit serum albumin and a saturated solution of ammonium sulphate is used for separation. The reliability criteria of the method in terms of precision, accuracy, sensitivity and specificity have been evaluated.

The mean level of testosterone in plasma samples from nineteen normal men (age range 16–73 years) is 527±226 (±SD) ng/100 ml. In ten normal ambulatory females (in the second phase of the cycle) aged 19–35 years the mean plasma testosterone is 27±8±10±6 (±SD) ng/100 ml. In twenty‐four impotent men (aged 18–50) the testosterone level is 431±191 (mean±SD) ng/100 ml. These values are not significantly different from normal subjects.

Lastly, the testosterone levels found in a few cases of male hypogonadism are reported.
THE USE OF THE E‐ROSETTE AS A TEST FOR REMISSION IN GRAVES’DISEASE TREATED WITH ANTITHYROID DRUGS
Authors: FARID NADIR R. , MUNRO ROBERT , ROW VAS V. , VOLPÉ ROBERT
Published: March 2008

E‐rosettes (T‐lymphocytes) have been demonstrated to be increased in the peripheral blood of patients with untreated Graves’disease and decreased when these patients go into remission induced by antithyroid drugs. In patients similarly treated but not in remission, a high percentage of E‐rosettes persisted. The degree of suppression by T3 of the thyroidal 131I uptake correlated well with the percentage of E‐rosettes. We suggest that E‐rosette counts may prove to be a useful test for detecting remissions in thyrotoxic patients treated with antithyroid drugs.
A COMPARISON OF EFFECTIVE THYROXINE RATIO, FREE THYROXINE INDEX AND FREE THYROXINE CONCENTRATION IN CORRECTING FOR THYROXINE‐BINDING ABNORMALITIES IN SERUM
Authors: WELLBY M. L. , O'HALLORAN M. W. , MARSHALL JANET
Published: March 2008

The effective thyroxine ratio (ETR), a single test of thyroid function which has a highly significant linear correlation with serum free thyroxine (T4) concentration, was assessed for its effectiveness in distinguishing the euthyroid state in subjects with abnormalities of T4‐binding proteins.

In patients with low activity of T4‐binding proteins, the diagnostic accuracy of the ETR (80±5%) is superior to that of the free T4 index (62±5%) and free T4 concentration (67%). In patients with elevated T4‐binding proteins the diagnostic accuracy of ETR was even higher at 93±5% and again better than the free T4 index (83%) and the free T4 concentration (91%).
COMPARISON OF THE EFFECTS OF ETHINYL OESTRADIOL AND CONJUGATED EQUINE OESTROGENS IN OOPHORECTOMIZED WOMEN
Authors: BOLTON C. H. , ELLWOOD M. , HARTOG M. , MARTIN R. , ROWE A. S. , WENSLEY R. T.
Published: March 2008

Seventeen oophorectomized women were treated for 3 month periods, in random sequence, with ethinyl oestradiol 20 and 50 μg daily and conjugated equine oestrogens (Premarin) 0.625 and 1.25mg daily. The serum cholesterol, clot lysis time, plasma fibrinogen, platelet adhesiveness and activated partial thromboplastin time remained unchanged throughout the different oestrogen regimes. There was a significant rise of serum triglyceride levels on both doses of ethinyl oestradiol but no significant change with Premarin. Serum luteinizing hormone levels were depressed most by ethinyl oestradiol 50 μg daily, although not down to the levels in premenopausal women.
ADRENOCORTICAL RESPONSE DURING EXAMINATION
Authors: BASEER A. , RAB S. M.
Published: March 2008

The stressful effect of a written and oral examination was studied in twenty‐two doctors sitting a postgraduate examination. The rise in the plasma cortisol was not significant in the written examination and reverted to normal values after an hour. On the other hand, there was a significant rise in the plasma cortisol during the oral examination with a pre‐enry rise in blood sugar and a fall in α‐amino nitrogen. It is concluded that whereas a written examination is not a stressful situation, an oral examination is stressful enough to be comparable to rowing and flying.
THE OESTROGEN PROVOCATION TEST
Authors: SHAW R. W. , BUTT W. R. , LONDON D. R. , MARSHALL J. C.
Published: March 2008

The oestrogen feedback and gonadotrophin release in ten amenorrhoeic women were investigated, using intramuscular injection of 1 mg oestradiol benzoate. Serial estimations of serum oestradiol and gonadotrophins (LH and FSH) were made over a period of 72 h following the injection. Five patients demonstrated positive feedback release of LH to the oestrogen stimulus with elevated levels of LH significantly above baseline (P<0.001), which occurred between 48 and 72 h after the injection. Two of the five patients also demonstrated elevated FSH levels accompanying these LH peaks. The hypothalamic‐pituitary axis was postulated to be intact in these five patients, and all ovulated on clomiphene.

None of the remaining five subjects showed any increase in serum gonadotrophin levels in response to oestradiol and none ovulated on clomiphene when given a dose of up to 200 mg daily × 5 days.

This ‘oestrogen provocation test’ seems to be a useful means of evaluating the functional capacity of the hypothalamic‐pituitary axis for gonadotrophin release and has proved useful in predicting responsiveness to clomiphene in amenorrhoeic women.
CHRONIC TREATMENT REGIMENS FOR HIRSUTISM IN WOMEN: EFFECT ON BLOOD PRODUCTION RATES OF TESTOSTERONE AND ON HAIR GROWTH
Authors: CASEY JOHN H.
Published: March 2008

Twenty‐five women with hirsutism were studied before and during treatment aimed empirically at suppressing testosterone production by adrenals, ovaries or both. Mean basal plasma testosterone was 70 ± 30 ng/dl, significantly (P<0.01) higher than the mean of twenty‐three normal women; basal metabolic clearance rate (MCR) of testosterone was also higher (P<0.01) than that reported for normal women. Production rate (PR) of testosterone exceeded 417 μg/24 h (1 SD above the mean reported for normal women), in nineteen of the twenty‐five patients. After 4 months, small dose betamethasone therapy (0.5 mg at bed time) had reduced the mean PR of testosterone in thirteen patients from 509 μg/24 h to 356 μg/24 h (P= 0.05); anovulatory steroids reduced mean PR of testosterone in nine from 612 μg/24 h to 345 μg/24 h (P<0.05, >0.025), and the combination of both therapies in ten reduced PR of testosterone from 528 μg/24 h to 148 μg/24 h (P<0.001). The latter regimen had moderate success in reducing hair growth (in six out of ten). Fourteen of the twenty‐five claimed benefit in hirsutism and all thirteen with acne were improved. In individual cases, clinical benefit did not correlate well with reduction in PR of testosterone. Freedom from undesirable side effects allows these well‐accepted forms of treatment to be given even longer trials.
BIOSYNTHESIS OF OESTROGENS AND THEIR INTER‐CONVERSION IN HUMAN PLACENTAE FROM NORMAL AND TOXAEMIC PREGNANCIES
Authors: RAHMAN S. A. , HINGORANI V. , LAUMAS K. R.
Published: March 2008

In vitro biosynthesis of oestrogens in microsomal and 10000 g supernatant fractions of placentae, ten each, from normal and toxaemic pregnancies has been investigated. Dehydroepiandrosterone sulphate (DHAS), dehydroepiandrosterone (DHA) and androstenedione were used as substrates and their conversion to oestrone and oestradiol studied. In all the placental preparations the relative efficiency of the conversion of these androgens to oestrogens, though differing greatly between subcellular fractions as well as between normal and toxaemic placentae, was invariably in the order of DHAS > DHA > androstenedione. The conversion of these androgen precursors to oestrone and oestradiol was reduced in toxaemia compared with the normal placenta. Moreover, formation of oestradiol was much more reduced than that of oestrone. The free oestradiol level in the serum was also found to be lower in toxaemic pregnancies as compared with the normal range. The inter‐conversions of oestrogens further showed a significantly reduced conversion of oestrone to oestradiol in toxaemic placentae compared with normal placentae. The results may explain the lowered blood oestradiol levels observed in toxaemia of pregnancy and thus provide an explanation of the usefulness of the estimation of the oestradiol level as an index of feto‐placental function.