bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOW‐DOSE PITUITARY IRRADIATION FOR ACROMEGALY
Authors: LITTLEY M. D. , SHALET S. M. , SWINDELL R. , BEARDWELL C. G. , SUTTON M. L. 
Published: March 2008

SUMMARYExternal radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n=23) or 35‐40 Gy in 15 fractions over 21 days (n=47). Growth hormone hypersecretion was either unchanged or increased with time in non‐irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to < 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre‐radiotherapy GH level of < 30 mU/1 showed a significantly increased probability of achieving a post‐ radiotherapy GH level < 5 mU/1 (P=0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation‐induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH‐secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.
AMINOPROPYLIDINE DIPHOSPHONATE (APD) IN MILD PRIMARY HYPERPARATHYROIDISM: EFFECT ON CLINICAL STATUS
Authors: SCHMIDLI R. S. , WILSON I. , ESPINER E. A. , RICHARDS A. M. , DONALD R. A. 
Published: March 2008

SUMMARYMild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non‐specific. Accordingly, we employed the hypocalcaemia effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo‐controlled cross‐over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49±0.04 SEM mmol/l) after APD when compared to control values (2.70±0.06 mmol/l, P< 0.001). Twenty‐four‐hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P <0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side‐effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients.
THE EFFECT OF OXYTOCIN INFUSION ON ADENOHYPOPHYSEAL FUNCTION IN MAN
Authors: PAGE S. R. , ANG V. T. Y. , JACKSON R. , WHITE A. , NUSSEY S. S. , JENKINS J. S. 
Published: March 2008

SUMMARYThe responses of the adenohypophyseal hormones adrenocorticotrophin (ACTH), growth hormone (GH), thyroid stimulating hormone (TSH), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) to sub‐maximal doses of hypothalamic releasing factors were studied in six lean male volunteers (age 23‐35 years) with and without infusions of oxytocin (OXT). OXT infusion (mean plasma concentration 133.6±2.6 pmol/1) completely inhibited the plasma ACTH responses to corticotrophin releasing hormone (CRH) (saline, peak increment ACTH 1.61±0.75 pmol/l; OXT, peak increment ACTH — 0.04±0.28 pmol/l; P < 0.05). OXT infusion had no significant effect on the GH response to growth hormone releasing hormone (GHRH), the TSH and prolactin responses to thyrotrophin releasing hormone (thyroliberin, TRH) or the LH and FSH responses to gonadotrophin releasing hormone (luteoliberin, GnRH). The data support a role for OXT in the modulation of ACTH secretion in man.
IMPAIRED SECRETION OF PARATHYROID HORMONE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RELATIONSHIP TO INFLAMMATORY ACTIVITY
Authors: EKENSTAM EVA AF , BENSON LARS , HÄLLGREN ROGER , WIDE LEIF , LJUNGHALL SVERKER 
Published: March 2008

SUMMARYHypocalcaemic tests, employing infusion of EDTA over 1 h, were performed in 22 patients with rheumatoid arthritis (RA) and 14 healthy controls. The basal levels of calcium and parathyroid hormone (PTH) were not significantly different in the two groups. The RA patients displayed a markedly impaired PTH response during infusion of EDTA compared with the controls although the reduction of plasma ionized calcium was similar. The PTH response was furthermore significantly, inversely, related to the inflammatory activity measured as sedimentation rate (r= 0.65; P < 0.01), i.e. the more pronounced the inflammation, the less the capacity to secrete PTH. Since secretion of PTH is related to the intracellular calcium concentration of the parathyroid cells, these findings are in line with previous observations of a higher intracellular calcium content in inflammatory disease. They also support the earlier indications of reduced bone turnover in inflammatory arthritides. An insufficient parathyroid function could be one factor contributing to bone disease in these conditions.
PROLONGED TREATMENT WITH THE GnRH ANALOGUE BUSERELIN DOES NOT AFFECT α‐SUBUNIT PRODUCTION BY THE PITUITARY GONADOTROPH
Authors: KWEKKEBOOM D. J. , LAMBERTS S. W. J. , BLOM J. H. M. , SCHROEDER F. H. , DE JONG F. H. 
Published: March 2008

SUMMARYSeven patients with metastatic prostatic cancer were treated with biodegradable implants of the GnRH analogue buserelin and six were treated with buserelin intranasally. After 4‐24 weeks of treatment mean serum testosterone concentrations were significantly lower in the patients treated with implants than in those treated intranasally (0.7 vs 1.7nmol/1 respectively; P < 0.01). Also, serum LH concentrations were significantly lower in the group treated with implants. Serum α‐subunit concentrations were significantly higher than pretreatment values during buserelin treatment. However, the sum of the concentrations of α‐subunit present either as free α‐subunit or as a part of LH did not differ significantly from pre‐treatment values after 8 weeks or more of buserelin treatment. During buserelin treatment serum LH concentrations measured by radioimmunoassay (RIA) were higher than those measured by immunoradiometric assay (IRMA). Cross‐reactivity of α‐subunit in the LH RIA accounted for many, but not all, of the observed discrepancies. We conclude that: (1) the principal long‐term effect of prolonged buserelin administration on the pituitary gonadotroph is the suppression of LHβ production, while α‐subunit production is not affected; (2) the serum concentrations of bioactive LH are better reflected by LH concentrations measured by IRMA than by those measured by RIA. (3) Subcutaneous application of biodegradable buserelin implants is more effective in suppressing serum LH and testosterone concentrations than intranasal buserelin application.
THE LOSS OF CIRCADIAN RHYTHM FOR INTACT PARATHYROID HORMONE AND NEPHROGENOUS CYCLIC AMP IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM
Authors: LOGUE F. C. , FRASER W. D. , GALLACHER S. J. , CAMERON D. A. , O'REILLY D. St J. , BEASTALL G. H. , PATEL U. , BOYLE I. T. 
Published: March 2008

SUMMARYThe measurement of serum intact parathyroid hormone (PTH) (1‐84) over a 24‐h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N‐cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1‐84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1‐84) secretion.
EFFECT OF ORAL GLUCOSE ON THE LATE GROWTH HORMONE RISE AND GROWTH HORMONE RESPONSES TO GHRH IN NORMAL SUBJECTS
Authors: VALCAVI R. , ZINI M. , DIEGUEZ C. , PORTIOLI Í. , SCANLON M. F. 
Published: March 2008

SUMMARYA late rise in serum GH occurs 3‐5 h following oral glucose in man. In order to investigate the mechanisms through which this occurs we have studied the late GH rise after oral glucose during administration of a supramaximal dose of GHRH. In eight normal subjects, oral glucose (100 g) greatly enhanced the GH responses to a supramaximal dose of GHRH (50 μg bolus, followed immediately by 100 μg/h infusion for 3 h) given 3.5 h after the glucose. GH peak (mean±SEM) elicited by GHRH (bolus + infusion) rose from 55.2±20.4 to 133.4±29.6 mU/1 (P< 0.02) after glucose pretreatment. In conclusion, it is likely that the late rise in GH secretion induced by oral glucose occurs via a non‐GHRH‐dependent mechanism. These data are consistent with the hypothesis that the delayed GH response to glucose is a consequence of reduced release of somatostatin from the hypothalamus.
PHARMACOKINETICS OF THE LONG‐ACTING SOMATOSTATIN ANALOGUE OCTREOTIDE (SMS 201‐995) IN ACROMEGALY
Authors: NICHOLLS J. , WYNICK D. , DOMIN J. , SANDLER L. M. , BLOOM S. R. 
Published: March 2008

SUMMARYA single‐dose study was performed to examine the pharmacokinetics of subcutaneous octreotide in acromegalic patients and to investigate the relationship between growth hormone and the elimination half‐life of the drug. Fourteen acromegalic patients (six men and eight women; age range 35‐59 years) who had previously received conventional treatment were studied. Two subjects were on long‐term octreotide which had been discontinued 72 h before the study. Octreotide 100 μg was administered subcutaneously and plasma samples taken every 10 min for 1 h and then hourly for up to 8 h. Growth hormone was measured at 0, 2 and 8 h. Octreotide was rapidly absorbed with a mean (± SEM) t1/2abs of 5‐4 min (± 0.8) peaking at a mean plasma concentration of 3.4 nmo1/1 (± 0.2) in 27.4 min (± 3.7). The monoexponential elimination phase had a mean half‐life of 110 min (± 9.6). The apparent volume of distribution was 29.4 1 (± 1.9) and total clearance was 172 ml/min (± 10.4). These results were similar to those obtained in normal volunteers. There was no simple relationship between the level of growth hormone and the half‐life of octreotide. Growth hormone levels ranged from 2.5 to 34.0 mIU/1 but were only > 10 mIU/l in three subjects. Further studies of octreotide pharmacokinetics are needed in untreated patients with acromegaly with raised growth hormone levels.
LONG‐TERM FOLLOW‐UP OF‘CURED’PROLACTINOMA PATIENTS AFTER SUCCESSFUL ADENOMECTOMY
Authors: CICCARELLI ENRICA , GHIGO EZIO , MIOLA CATALDO , GANDINI GIOVANNI , MULLER EUGENIO E. , CAMANNI FRANCO 
Published: March 2008

SUMMARYThe long‐term follow‐up (±Mg4 years) of clinical, hormonal and radiological aspects in 22‘cured’prolactinoma patients after adenomectomy was studied. Dynamic secretion of PRL and TSH was also evaluated, in order to identify the persistence of any underlying abnormality of hypothalamic pituitary control and to predict relapses. A relapse into hyperprolactinaemia was shown in 36% of patients 5‐90 months (mean 46) after surgery. This was accompanied by reappearance of clinical symptoms but not by the radiological demonstration of the adenoma in any patients. A significant PRL rise after domperidone, a dopaminergic antagonist drug, was shown in cured patients after surgery (mean±SEM peak, 2977±645 mU/1) but this was markedly lower than that observed in control subjects (5732±440 mU/1). In fact, normal PRL increments were shown in only 6/16 (37%) patients. TSH hyper‐responsiveness to domperidone normalized in only 46% of patients. Similar PRL responses to those obtained with domperidone were shown when a TRH test was given. A relapse into hyperprolactinaemia was observed in six of ten (60%) non‐responders to domperidone and in four of seven (57%) non‐responders to TRH, whereas six normal responders to domperidone and TRH had not relapsed at that time. Plasma PRL levels during pregnancy showed increments lower than those observed in normal pregnant women only in domperidone and TRH non‐responder patients. These results indicate that a relapse into hyperprolactinaemia and a blunted PRL rise during pregnancy were present only in patients with persistently reduced PRL response to dynamic tests.
SERUM FREE 1,25‐DIHYDROXYVITAMIN D AND THE FREE 1,25‐DIHYDROXYVITAMIN D INDEX DURING A LONGITUDINAL STUDY OF HUMAN PREGNANCY AND LACTATION
Authors: WILSON SCOTT G. , RETALLACK ROBERT W. , KENT JACQUELINE C. , WORTH GRAEME K. , GUTTERIDGE DONALD H. 
Published: March 2008

SUMMARYThe changes in three different indices of 1,25‐dihydroxyvitamin D (1,25(OH)2D) biological activity were studied longitudinally in 35 women during late pregnancy and lactation and in 26 control women. Measurements were made of maternal serum total 1,25(OH)2D and free 1,25(OH)2D concentration (by centrifugal ultrafiltration) and the free 1,25(OH)2D index (the molar ratio of total 1,25(OH)2D and vitamin D binding protein (DBP)). During late pregnancy total 1,25(OH)2D concentrations were significantly elevated when compared to controls, as were free 1,25(OH)2D and DBP concentrations and the free 1,25(OH)2D index. Serum total 1,25(OH)2D, free 1,25(OH)2D and DBP concentrations all fell dramatically during the first 2 weeks of lactation with total 1,25(OH)2D and free 1,25(OH)2D concentrations falling to levels below those of controls. During the course of lactation both total I,25(OH)2D and free 1,25(OH)2D levels rose significantly although they were not different from controls at 18 weeks of lactation. In contrast, the free 1,25(OH)2D index fell during the first 2 weeks of lactation, but remained at this level, significantly lower than controls. Neither urinary calcium excretion nor dietary calcium intake correlated with total or free 1,25(OH)2D, DBP, or the free 1,25(OH)2D index. The disagreement in the results of free 1,25(OH)2D concentration and free 1,25(OH)2D index demonstrates that these two approaches to measuring biologically active 1,25(OH)2D are not equivalent. In attempting to account for the increased calcium requirements of human reproduction we conclude that in pregnancy any of the 1,25(OH)2D measurements may be appropriate. In lactation, however, either 1,25(OH)2D is not a major factor or 1,25(OH)2D biological activity is inadequately represented by any of the currently available methods.
POTENCY AND SELECTIVITY OF THE NON‐STEROIDAL AROMATASE INHIBITOR CGS 16949A IN POSTMENOPAUSAL BREAST CANCER PATIENTS
Authors: DOWSETT M. , STEIN R. C. , MEHTA A. , COOMBES R. C. 
Published: March 2008

SUMMARYA selective inhibitor of aromatase is widely sought for the treatment of postmenopausal women with breast cancer. CGS 16949A has been shown to be a highly selective, potent inhibitor of aromatase in vitro. Its potency as an oestrogen suppressant and its selectivity were examined by treating 24 postmenopausal patients with advanced breast cancer for 4 weeks with doses of 0.3, 1‐0 and 2‐0 mg twice daily. The study was conducted in two parts which compared the two lower doses and the two higher doses separately in a cross‐over design protocol. All doses significantly suppressed serum oestradiol and oestrone levels below pretreatment levels. Cross‐over analysis indicated that the 2.0 mg twice daily dose achieved significantly greater suppression of oestradiol levels than 1‐0 mg twice daily but there was no significant difference between any of the doses in the suppression of oestrone. No significant effects were noted on serum levels of LH, FSH, SHBG, prolactin, testosterone, androstenedione, 17‐ hydroxyprogesterone or cortisol. For the four steroids this was true both for basal samples and those collected after Synacthen stimulation. However, serum aldosterone levels were significantly suppressed by 1‐0 mg twice daily CGS 16949A and further suppressed by 2‐0 mg twice daily. It is concluded that CGS 16949A is a potent oestrogen suppressant in postmenopausal patients but that its effect is not totally selective.
RELATIVE CHANGES IN LH PULSATILITY DURING THE MENSTRUAL CYCLE: USING DATA FROM HYPOGONADAL WOMEN AS A REFERENCE POINT
Authors: ROSSMANITH W. G. , LIU C. H. , LAUGHLIN G. A. , MORTOLA J. F. , SUH B. Y. , YEN S. S. C. 
Published: March 2008

SUMMARYThe basic premise of this study is that the GnRH‐LH pulsatile activity, particularly its frequency characteristics, constitutes, in the absence of any considerable ovarian feedback, the intrinsic rhythm of the hypothalamic‐pituitary unit at its maximal rate. Thus, LH pulse attributes determined in postpubertal hypogonadal subjects may be used as a reference in assessing the degree of influence exerted by endocrine factors that modulate GnRH‐LH pulses. Accordingly, serum LH levels were determined in samples obtained at 15‐min intervals for 24 h in 20 hypogonadal women: 13 postmenopausal women (PMW) and seven women with premature ovarian failure (POF). Similar measurements were performed in 60 normally cycling women: 25 in the early follicular phase (EFP), 13 in the late follicular phase (LFP), seven at midcycle surge (LH surge) and 15 in the midluteal phase (MLP). Significant pulses were identified by the cluster algorithm utilizing factors appropriate for 24 h data series of a sampling frequency of 15‐min intervals. The results show a 24‐h mean (± SE) LH pulse frequency of 78.2±2.8 and 85.5±2.4 min per pulse for young (POF) and older (PMW) hypogonadal women, respectively. During the follicular phase of the cycle, the LH pulse frequency is not significantly different from that of hypogonadal women, but there is a significant (P < 0.05) increase from early to late follicular phases (95.4±3.3 vs 78.8±2‐2 min per pulse). However, when the sleep periods are excluded from the 24‐h data series because of the associated decrease of LH pulse frequency in EFP women, the resulting pulse frequencies are almost identical for EFP, LFP and PMW. An elevation beyond the basic pulse rhythm determined in PMW or POF is not observed in any phase of the menstrual cycle studied, including the midcycle surge. The decrease in LH pulse frequency during the luteal phase of the cycle (151.8±8.0 min per pulse, P < 0.001 vs hypogonadal women) beyond the reference pulse frequency of hypogonadal women is unequivocal. By contrast, the pulse amplitude varies markedly among the groups with the largest found in POF (36.6±4.5 IU/1). It follows, in descending order, PMW (22.7±3.1 IU/1), midcycle surge (17.3±2.8 IU/1), MLP women (7.0±1.3 IU/1) and the EFP (4.9±0.3 IU/I) and LFP (4.0 ±0.4 IU/I). These data support the concept that the changes in the LH pulse frequency during the menstrual cycle can be reduced, but do not exceed the periodicity of the basic rhythm of the GnRH‐LH pulse generator determined in hypogonadal women. Our observations also demonstrate that the pulse amplitude is subject to profound modulation by ovarian factors. Thus, the basic rhythm of GnRH‐LH pulses may serve as a meaningful reference in assessing influences by endocrine factors on GnRH‐LH pulsatile activity.
RELATIONSHIP BETWEEN SOMATOSTATIN AND GROWTH HORMONE MESSENGER RIBONUCLEIC ACID IN HUMAN PITUITARY ADENOMAS: AN IN‐SITU HYBRIDIZATION HISTOCHEMISTRY STUDY
Authors: LEVY A. , LIGHTMAN S. L. 
Published: March 2008

SUMMARYWe have used quantitative in‐situ hybridization histochemistry to assess the somatostatin (SRIH) and GH messenger ribonucleic acid (mRNA) content of 81 pituitary adenomas. SRIH mRNA was found in the absence of GH mRNA in only one tumour and in the five cases in which GH and SRIH mRNA were both present, SRIH mRNA prevalence was approximately two orders of magnitude less than GH mRNA. However, no direct correlation between GH mRNA, SRIH mRNA and circulating GH levels was evident at the time of surgery. In contrast, there was no detectable SRIH mRNA probe binding to a thyrotroph adenoma, a gonadotroph adenoma, 29 endocrinologically inactive pituitary adenomas, nine lactotroph adenomas, two first trimester fetal and two normal adult pituitary glands obtained 24 and 36 h post‐mortem. These findings corroborate previous reports of SRIH release from somatotroph adenomas in vitro and suggest that paracrine or autocrine mechanisms linking SRIH and GH mRNA operate within normal pituitary tissue. As somatotroph adenomas are thought to be predominantly clonal in origin, the data further suggest that GH and SRIH are synthesized in the same or closely related cells.
RADIOIMMUNOASSAY MAY OVERESTIMATE INSULIN IN NON‐INSULIN‐DEPENDENT DIABETICS
Authors: TEMPLE ROSEMARY C. , CLARK PENELOPE M. S. , NAGI DINESH K. , SCHNEIDER ANNEROSE E. , YUDKIN JOHN S. , HALES C. NICHOLAS 
Published: March 2008

SUMMARYWe have compared insulin concentrations measured by radioimmunoassay (RIA) in plasma from 50 fasting non‐insulin‐dependent diabetics (NIDDM) with those measured by a new monoclonal antibody‐based two‐site immunoradiometric assay (IRMA) of insulin (which has no significant cross‐reaction with proinsulin‐like molecules). We find that the RIA measures the sum of the insulin and proinsulin like molecules and that the IRMA insulin concentrations are 38% of those measured by the RIA in those diabetic subjects. We conclude that the importance of insulin deficiency in NIDDM may have been obscured by this error.