bluuebunny/crossref_metadata_2025_split huggingface dataset:
FASTING HYPERGLYCAEMIA AND RELATIVELY UNIMPAIRED MEAL RESPONSES IN MILD DIABETES
Authors: TURNER R. C. , MANN J. I. , SIMPSON R. D. , HARRIS E. , MAXWELL R. 
Published: March 2008

SUMMARYPlasma glucose, insulin and triglyceride changes in response to a standard breakfast and an oral glucose tolerance test have been studied in normal, obese and diabetic subjects. Mild diabetics with an abnormal oral glucose tolerance test may have normal or near‐normal incremental glucose responses to a standard breakfast. A raised fasting plasma glucose is the predominant day‐to‐day glucose abnormality of mild diabetes. Diabetics have decreased insulin responses to oral glucose compared with the meal, and the deficient insulin response to glucose probably accounts for both the raised fasting plasma glucose levels and the abnormal oral GTT. The initial insulin response to a meal is normal in mild diabetics, and is probably stimulated by secretogogues other than glucose. The oral glucose tolerance test is apposite for the diagnosis of diabetes in view of the impaired insulin response to glucose, but accurate measurement of the basal plasma glucose may be of equal value. The diabetic and obese subjects had normal triglyceride levels, and there was no detectable impairment of disposal of the exogenous triglyceride following the breakfast.
PENILE SIZE AND GROWTH IN CHILDREN AND ADOLESCENTS WITH ISOLATED GONADOTROPHIN DEFIENCY (IGnD)
Authors: LARON ZVI , KAUSHANSKI ARIE , JOSEFSBERG ZEEV 
Published: March 2008

SUMMARYPenile length and circumference were measured in twenty boys with isolated gonadotrophin deficiency, before and during the administration of androgen therapy. Their age ranged between 3 and 20 years. Considering as normal, measurements above the tenth centile, in all the patients but four the penile length was below normal, and in two it was borderline. Penis circumference was normal in two, borderline in four and subnormal in sixteen. Regular administration of androgen therapy increased penile length in eleven out of fourteen patients with achievement of normal length in four.It is concluded that congenital lack of LH and testicular androgen activation causes small sized penises, even in the prepubertal period. Gonadotrophin deficiency should be looked for in patients with measurements below the tenth centile. Early diagnosis and institution of androgen therapy between 11 and 12 years is likely to increase penile size and prevent the psychological side effects of undersized genitals and delayed puberty.
THE COMBINED EFFECT OF GROWTH HORMONE AND METHANDROSTENOLONE ON THE LINEAR GROWTH OF PATIENTS WITH MULTIPLE PITUITARY HORMONE DEFICIENCIES
Authors: PERTZELAN A. , BLUM I. , GRUNEBAUM M. , LARON Z. 
Published: March 2008

SUMMARYSix patients with multiple pituitary hormone deficiencies (MPHD) were initially treated with separate courses of methandrostenolone and growth hormone and later with the two drugs combined. During the basal period the mean growth velocity was 2.8 cm/year. Methandrostenolone alone, 0.02‐0.05 mg/kg/day given to four of the patients led to an acceleration of the growth velocity to a mean of 5.0 cm/year, while growth hormone 6 mg/week alone accelerated the growth rate to a mean of 6.0 cm/year. Combined therapy led to a striking increase in the mean growth rate to 9.3 cm/year. The shortcoming of the combined growth hormone‐androgen therapy was the fast acceleration in skeletal maturation even after short‐term administration.
GONADAL FUNCTION IN BLOOM'S SYNDROME
Authors: KAULI R. , PRAGER‐LEWIN R. , KAUFMAN H. , LARON Z. 
Published: March 2008

SUMMARYFive patients with Bloom's syndrome aged from 2 8/12 to 27 years, all of whom had hypogonadism, were subjected to an i.v. LHRH test and two of them to an i.m. HCG test. There was increased responsiveness of plasma LH and FSH, indicating that the hypogonadism is primary in nature and of early development. The tubular element of the testis seems to be mainly affected, as indicated by the particularly high FSH response to LHRH stimulation, a history of sterility in the two adult patients and documented azoospermia in one of them. The Leydig cells seem to be less affected and secrete sufficient androgens to enable puberty within acceptable normal limits. Hypogonadism seems to be a major characteristic of Bloom's syndrome.
NORMAL PLASMA CALCITONIN: CIRCADIAN VARIATION AND RESPONSE TO STIMULI
Authors: HILLYARD CARMEL J. , COOKE T. J. C. , COOMBES R. C. , EVANS IMOGEN M. A. , MACINTYRE I. 
Published: March 2008

SUMMARYA simple, reproducible extraction method has been developed, which is capable of measuring calcitonin in normal individuals. Normal calcitonin levels show a circadian variation, with a peak around midday and respond to known stimuli for calcitonin release.
EVALUATION OF 3 HOUR METYRAPONE TEST IN CHILDREN AND ADOLESCENTS
Authors: LEISTI SEPPO 
Published: March 2008

SUMMARYAn evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00‐09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty‐five reference subjects, in thirty‐six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication.During the first hour after metyrapone the plasma cortisol level decresed to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally < 35 nmol/1 and increased continously during the 3 h period to the mean level of 299 (95% confidence interval 133‐669) nmol/1 in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency.No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia.
GONADOTROPHIN RELEASE IN OVARIECTOMIZED PATIENTS
Authors: RAVID R. , JEDWAB G. , PERSITZ E. , DAVID M. P. , KARNI N. , GIL S. , CORDOVA T. , HARELL A. , AYALON D. 
Published: March 2008

SUMMARYAdministration of clomiphene citrate (150 mg/day) for 5 days to twenty‐four ovariectomized patients and seven normal female patients evoked a significant release of FSH and LH in the normal control group and suppressed the gonadotrophin secretion in the castrated patients. A similar suppressive effect on gonadotrophin secretion was noted in eight ovariectomized patients treated for 10 days with low doses (50 μg/day) of ethinyl oestradiol.It is suggested that in the ovariectomized hypoestrogenic patients, clomiphene acted as an oestrogen, suppressing by a negative feedback action gonadotrophin release in a way similar to ethinyl oestradiol. In the normal control group with an adequate steroid environment, clomiphene acted (probably at the hypothalamic level) as an oestrogen antagonist and stimulated gonadotrophin secretion. In view of our findings, it seems as if the ability of anovulatory patients to respond to clomiphene treatment by increased gonadotrophin secretion depends upon the absolute concentration of the compound in the different organs and by the quantitative relation of clomiphene to the endogenous oestrogens.There is still a considerable degree of uncertainty about the exact mode of action of clomiphene (1‐[p‐β‐diethyl‐aminoethoxyphenyl]‐1,2, dipheny1‐2 chloroethylene citrate) a non‐steroidal oestrogen antagonist. However, it appears increasingly evident that this compound which possesses antioestrogenic properties acts probably in an indirect manner, by competing with oestradiol for the receptor sites at the hypothalamic centres regulating gonadotrophin secretion, thus stimulating gonadotrophin releasing hormone (LHRH) secretion, with a subsequent release of FSH and LH (Igarashi et al., 1967; Seki et al., 1970).By contrast, in prepubertal children, a paradoxical suppression of both LH and FSH release was demonstrated following administration of clomiphene (Kelch et al., 1971). The explanation offered for this phenomenon was that the immature hypothalamic gonadostat is hypersensitive to sex steroids, and as clomiphene has intrinsic oestrogenic properties, it could account for the unexpected gonadotrophin suppression rather than stimulation in the prepubertal child. A similar effect could be obtained in prepubertal children by administration of low doses of oestrogens (Kelch et al., 1971).In order to gain additional information on the mode of action of clomiphene at the hypothalamic and pituitary levels, we studied the effect of clomiphene and of low doses of oestrogens on LH and FSH release in ovariectomized patients. These patients provide a suitable model for the investigation of the mode of action of clomiphene on a normal hypothalamic‐pituitary system in an environment free of gonadal steroid (Tepperman, 1973).
DECREASED SERUM THYROID HORMONE LEVELS AND INCREASED TSH RESPONSE TO TRH IN INFANTS WITH COELIAC DISEASE
Authors: VANDERSCHUEREN‐LODEWEYCKX M. , EGGERMONT E. , CORNETTE C. , BECKERS C. , MALVAUX P. , EECKELS R. 
Published: March 2008

SUMMARYPlasma levels of thyrotrophin before and after the intravenous administration of 200 μg of thyrotrophin releasing hormone have been studied in eleven patients with active gluten‐induced enteropathy and in a group of twenty‐one normal prepubertal children. In nine out of eleven coeliac patients an exaggerated and/or sustained response of plasma thyrotrophin is observed. Basal plasma thyrotrophin level is not significantly different from the value observed in normal children. However, plasma levels recorded 20 and 60 min after injection of the releasing hormone are significantly higher than in control children (at 20 min: P<0.01; at 60 min: P<0.001). Serum levels of dialysed triiodothyronine and thyroxine and of triiodothyronine are significantly lower in coeliac patients than in normal infants (P<0.01). These data support the evidence of an endocrine dysfunction in coeliac disease. It is not clear whether it is due to malnutrition and/or to some direct action of circulating gluten‐peptides on the hypothalamus.Insulin‐induced growth hormone (GH) secretion is inadequate in most of the coeliac patients during the active phase of the disease and returns towards normal during recovery provided the diet is strictly glutenfree (Vanderschueren‐Lodeweyckx et al., 1973). These data, suggesting a dysfunction in the hypothalamo‐hypophyseal system during active coeliac disease, prompted us to study the release of thyrotrophin (TSH) induced by the administration of synthetic thyrotrophin releasing hormone (TRH) in patients with active coeliac disease.
THYROID HORMONE LEVELS AND PROTEIN BINDING IN PATIENTS ON LONG‐TERM DIPHENYLHYDANTOIN TREATMENT
Authors: HEYMA P. , LARKINS R. G. , PERRY‐KEENE D. , PETER C. T. , ROSS D. , SLOMAN J. G. 
Published: March 2008

SUMMARYThe effect of long‐term diphenylhydantoin (DPH) treatment on thyroid hormone concentrations and protein binding was determined in a randomized controlled trial. As has been demonstrated previously, total thyroxine (T4) concentrations were significanly depressed in patients on DPH. There was no significant effect on indirect indices of protein binding of thyroid hormones, and the free thyroxine index (FTI) was also significantly depressed. Triiodothyronine (T3) and thyrotrophin (TSH) concentrations were either unaffected, or only very slightly affected by DPH. Significant effects on the FTI were still apparent 4 weeks after discontinuing treatment. It is concluded that the depression of total T4 levels observed in vivo is not due solely to diminished protein binding, but may instead be largely explained by reports suggesting enhanced degradation of T4 following DPH therapy.Since 1961 it has been known that diphenylhydantoin (DPH) has a significant effect on the levels of the circulating thyroid hormones in the plasma (Oppenheimer et al., 1961). It is known that the effect is extrathyroidal (Oppenheimer et al., 1961) and it was initially assumed to be due to an effect on protein binding. This assumption followed the demonstration that DPH decreased the binding of thyroxine (T4) to throxine binding globulin (TBG) in vitro (Oppenheimer & Tavernetti, 1962). However, more recent work (Chin & Schussler, 1968; Larsen et al., 1970; Hansen et al., 1974; Stjernholm et al., 1975) has suggested that there may be a true depression of free T4.Most previous studies have been in epileptic patients for whom the control groups were not totally comparable (Hansen et al., 1974; Chin & Schussler, 1968) or in normal subjects who underwent DPH therapy for only a short time (i.e. 1‐2 weeks, Hansen et al., 1974). Moreover, DPH dosage in earlier studies has for the most part been arbitrarily decided upon, or evaluated by clinical signs. It is known that there are extremely variable individual responses to given doses of DPH (Richens & Dunlop, 1975), resulting in variable plasma levels of DPH.This study describes the effects of long‐term DPH treatment on thyroid function and thyroid hormone protein binding. A comparable control group was also studied, and DPH concentration in the blood was continually monitored. The same patients were reexamined after discontinuation of therapy, to elucidate the duration of the effect.
AN INVESTIGATION INTO GONADAL DYSFUNCTION IN PATIENTS WITH IDIOPATHIC HAEMOCHROMATOSIS
Authors: BEZWODA W. R. , BOTHWELL T. H. , VAN DER WALT L. A. , KRONHEIM S. , PIMSTONE† B. L. 
Published: March 2008

SUMMARYEndocrine studies were performed on twelve patients with proven idiopathic haemochromatosis. Basal gonadotrophin levels and/or their responses to LH releasing hormone (LHRH) were low in nine patients, all of whom showed low plasma testosterone levels and clinical evidence of hypogonadism. Those patients with normal gonadotrophin responses had higher testosterone values, suggesting that the poor testosterone secretion was primarily due to inadequate trophic stimulation. No patient showed hypothyroidism of hypothalamic‐pituitary origin, while the cortisol response to hypoglycaemia was normal in all six patients studied. GH responses were more variable and difficult to interpret, since the number of the patients studied was small and the degree of hypoglycaemia after insulin was unpredictable.While hypogonadism is extremely common in patients with long‐standing idiopathic haemochromatosis (Bricaire et al., 1971), there is some controversy as to its cause. Suggested aetiologies include functional disturbance at the hypothalamic or pituitary level (Tourniaire et al., 1974; Stocks & Powell, 1972), primary gonadal failure (Simon et al., 1972), or a combination of both (Simon et al., 1972; Walker et al., 1976). In an attempt to evaluate this problem, we have studied plasma gonadotrophin responses to both LH releasing hormone (LHRH) and clomiphene, and the plasma testosterone basally and after human chorionic gonadotrophin (HCG) in patients with proven haemochromatotis. The results of certain other tests of anterior pituitary function are also reported.
VASOVAGAL HYPOTENSION AND VASOPRESSIN RELEASE
Authors: WIGGINS R. C. , BASAR ISIK , SLATER J.D.H. , FORSLING MARY , RAMAGE C.M. 
Published: March 2008

SUMMARYMild vasovagal hypotension occurred in two normal male volunteers during insertion of indwelling venous cannulae. In spite of a rapid intravenous fluid load (3.6‐4.6 litres in 90 min) both subjects passed little urine for 100 min. When the experiment was repeated without vasovagal hypotension, a rapid large diuresis followed the fluid load. The prolonged oliguria after vasovagal hypotension was the result of vasopressin release. This was demonstrated by measuring vasopressin in the blood and urine and by observing the renal response to a water load. The observation in man that a mild transient hypotensive episode may reduce urine flow for 100 min has clinical significance.The control of vasopressin release is conventionally regarded as being dominated by the osmolality of the extracellular fuid; however, changes in plasma volume are also important (Johnson, Zehr & Moore, 1970; Share, 1967; Robertson & Athar, 1976). The existence of receptors in the left atrium and carotid sinus which provide the afferent limb to a neurogenic reflex mechanism for vasopressin release has been well established in animals (Henry et al., 1956; Mulcahy et al., 1973; Moran & Zimmerman, 1967), but little is known about their relevance to clinical situations in man. By chance we have been able to measure and observe the physiological effect of vasopressin released in response to a mild vasovagal hypotensive episode in two normal young men.
THE EFFECT OF ISOPRENALINE ON PLASMA RENIN ACTIVITY IN MAN: A DOSE‐RESPONSE CURVE
Authors: DAVIES ROY , SLATER J. D. H. , RUDOLF M. , GEDDES D. M. 
Published: March 2008

SUMMARYFour normal subjects on a free sodium intake received intravenous isoprenaline in doses of 2, 4, 8 and 16 μg over 2 min. Three of the subjects received a second infusion of 8 μg. The rate of renin release indexed by changes in plasma renin activity increased in all subjects at each dose level. The mean peak leveles of plasma renin were 9%, 29% and 77% above the mean control levels at doses of 2, 4 and 8 μMg respectively. The response of 16 μg was no different from that seen with 8 μg. The renin response obtained at 8 μg was highly reproducible such that the coefficient of variation for duplicate estimations of plasma renin (twelve duplicates) ranged from 1.7 to 4%.The rate of renin release from the kidney is known to be under adrenergic control (Vander, 1965; Wathen et al., 1965; Allison et al., 1970; Ueda et al., 1973) and recent studies in animals and man have indicated that an intrarenal beta‐adrenoreceptor mediates this release (Tobert et al., 1973; Inoue, 1973; Vandongen et al., 1973; Sabto et al., 1975). Isoprenaline is the archetypal beta‐adrenergic agonist with equal effects upon both beta1 and beta2 receptors (Lands et al., 1967). We have previously shown that minute bolus injections of this agent provokes renin release in normal people (Davies et al., 1975). However, there appears to have been no systematic investigation of a dose‐response relationship for the release of renin provoked by isoprenaline in man. The aim of this study was to attempt to define such a relationship and, mindful of the possible application of this technique to studies of the adrenergic control of renin release in patients, we have documented the reproducibility of this response.
COMPARISON OF THE PHARMACOKINETICS IN MAN OF TWO SYNTHETIC ACTH ANALOGES: a1–24 AND SUBSTITUTED β1–18 ACTH.
Authors: JEFFCOATE W.J. , PHENEKOS C. , RATCLIFFE J. G. , WILLIAMS SALLY , REES LESLEY , BESSER G.M. 
Published: March 2008

SUMMARYThe synthetic substituted corticotrophin analogue, a1–18 ACTH, was given intravenously or subcutaneously to thirteen human volunteers in whom endogenous secretion of ACTH had been suppressed with dexamethasone. Plasma levels of a1–18 ACTH over the succeeding 12–24 h were determined by radioimmunoassay and bioassy, together with the fluorometric corticosteroid responses. The plasma disappearance rate of a1–18 ACTH was compared with that of the corticotrophin fragment, a1–24 ACTH (tetracosactrin, Synacthen), in both unmodified and depot forms.Plasma levels of a1–18 ACTH were higher and were detectable for longer after intravenous rather than subcutaneous administration. The higher levels were associated with greater and more prologed corticosteroid responses. In addition, the corticosteroid response to the intravenous injection of 1 mg of a1–18 was greater and more prolonged than the response to the intravenous injection of the same dose of a1–24 ACTH. The plasma levels of immunoreactive a1–24 ACTH were not detectable for more than 4 h after this dose. After the intramuscular administration of 1 mg of the depot preparation, however, detectable plasma levels persisted for 12 h. It is concluded that the brief corticotrophic activity of unmodified a1–24 ACTH is due mainly to its rapid clearance from the circulation.There was no significant dissociation between the disappearance rates of immuno‐ and bio‐active a1–18 ACTH. This contrasted with a1–24 ACTH whose bioactivity disappeared from plasma significantly faster than immunoreactivity. This difference probably reflects the greater stability of a1‐18 ACTH In the circulation and this in turn accounts, in part at least, for its prolonged corticotrophic activity.In a separate study the peptides were given intranasally through special applicators to eleven dexamethasone suppressed volunteers. The plasma levels of a1–18 ACTH after a 1 mg dose were lower than when given by other routes but the corteroid response was unaltered. The corticosteroid response to a 1 mg dose of intranasal a1–24 ACTH was brief and similar to that which followed an intavenous or subcutaneous injection; it was not significantly prolonged if 5 mg was given. It is concluded that intranasal a1–24 ACTH is unlikely to be of value but itranasal a1–18ACTH may be therapeutically useful.
‘BIG ACTH’ AND CALCITONIN IN AN ECTOPIC HORMONE SECRETING TUMOUR OF THE LIVER
Authors: HIMSWORTH R. L. , BLOOMFIELD GLENYS A. , COOMBES R. C. , ELLISON MORAG , GILKES J. J. H. , LOWRY P. J. , SETCHELL K. D. R. , SLAVIN G. , REES LESLEY H. 
Published: March 2008

SUMMARYA young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and β‐MSH‐like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and ‘β‐MSH’ concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations.During the course of the illness the ectopic ACTH became biologically less potent. This ineffectual ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This ‘big ACTH’ differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C‐terminal antigenic determinant (33–39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this ‘big ACTH’ was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive β‐MSH‐like material and immunoreactive calcitonin which resembled calcitonin M chromatographically.
SYNCHRONOUS NYCTOHEMERAL RHYTHMS IN HUMAN BLOOD MELATONIN AND IN HUMAN POST‐MORTEM PINEAL ENZYME
Authors: SMITH J. A. , PADWICK D. , MEE T. J. X. , MINNEMAN K. P. , BIRD E. D. 
Published: March 2008

SUMMARYSerum melatonin was measured by radioimmunoassay at 4‐hourly intervals for 24 h in five normal men, and shown to exhibit nyctohemeral variations. The highest concentrations of serum melatonin occurred at 02.00 hours and the lowest concentrations at 14.00 hours. The synthetic enzymes for melatonin, serotonin‐N‐acetyl transferase (SNAT) and hydroxyindole‐O‐methyltransferase (HIOMT) were measured in post‐mortem pineal organs from thirty‐six men and women, and the activity of both enzymes was directly related to the time of death of the subject, resulting in a similar nyctohemeral curve as that observed with serum melatonin. The SNAT and HIOMT enzymes were stable when measured in pineal organs held under the usual post‐mortem conditions.These observations indicate a nyctohemeral rhythm in human pineal function and suggests that any clinical interpretation of pineal dysfunction in disease states should take into consideration this normal rhythm.