bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women
Authors: Williams Nancy I. , McArthur Janet W. , Turnbull Barry A. , Bullen Beverly A. , Skrinar Gary S. , Beltins Inese Z. , Besser G. Michael , Rees Lesley H. , Gilbert Ian , Cramer Derek , Perry Leslle , Tunstall Pedoe Dan S. 
Published: March 2008

SummaryOBJECTIVE Current studies reveal little regarding the Inception of exercise‐induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic–pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period.SUBJECTS All subjects were eumenorrhoelc, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid‐luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (V o2max = 38·0 ± 1·8) (mean ± SEM) ml/kg/min).DESIGN All women completed a 13·5‐hour pulsatility test which included three consecutive 20‐minute runs on a treadmill at 50, 60 and 70% of the subjects’maximum oxygen uptake (n= 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4·5 hours before and 8 hours after one hour of exercise and or strolling.MEASUREMENTS A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics.RESULTS Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0·05). Strolling produced no significant changes in LH secretion.CONCLUSION Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post‐exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse
p53 gene mutations in pituitary adenomas: rare events
Authors: Levy Andrew , Hall Leonard , Yeudall W. Andrew , Lightman Stafford L. 
Published: March 2008

SummaryOBJECTIVE Occult pituitary adenomas are said to occur in up to 20% of random autopsy examinations, yet the only oncogene known to be associated with pituitary adenomas, gsp, is found in only 40% of somatotrophinomas, a subtype that accounts for a minority of pituitary tumours. Mutations of the p53 tumour suppressor gene are thought to be involved in the pathogenesis of as many as 50% of all human cancers, including tumours of the central nervous system. The objective of this study was to determine whether p53 gene mutations are associated with pituitary adenomas.DESIGN AND PATIENTS Fragments of pituitary adenoma tissue from 29 patients undergoing routine hypophysectomy for pituitary tumour were coated in cryostat embedding medium and frozen at ‐80°C within 24 hours of resection. They consisted of 9 somatotroph, 4 corticotroph, 1 mammotroph and 15 endocrinologically inactive adenomas, all of the non‐invasive clinical phenotype. Sequential frozen sections were subjected to in situ hybridization analysis for anterior pituitary hormone transcripts and examined histologically to ensure that the frozen sections Used to generate DNA templates for polymerase chain reaction amplification were not contaminated with non‐tumour tissue.MEASUREMENTS p53 exons 7 and 8, within which 98% of substitution mutations are thought to occur, and exons 4–6 in tumours immunopositive for p53, were amplified by polymerase chain reaction and ligated Into the vector pCR2. DNA from small‐wale plasmid preparations of pCR2 containing cloned p53 exons from human pituitary adenomas was sequenced using an automated fluorescence‐based system (DuPont Genesis 2000) and compared with wild‐type sequence. Apparent mutations were confirmed or refuted by sequencing a further 2–4 clones isolated from the same template.RESULTS Although immunocytochemical staining patterns for wild‐type p53 varied markedly between different tumours, no mutations were identified in any of the exonic sequences examined.CONCLUSIONS p53 mutations, at least within the high mutation domains of p53, occur infrequently in human pituitary adenomas. Increased steady‐state levels of p53 protein identified immunocytochemically may be a consequence of binding to other cellular proteins in these tumours.
Quinagolide efficacy and tolerability in hyperprolactinaemic patients who are resistant to or intolerant of bromocriptine
Authors: Vilar L. , Burke C. W. 
Published: March 2008

SummaryOBJECTIVE To audit the efficacy of quinagoiide (CV205‐502, Norprolac, Sandoz) in lowering prolactin, and its tolerability, in patients with bromocriptine resistance (BCR) or bromocriptine intolerance (BCI), in view of the paucity of results published in patients specifically with BCR or BCI, by collating results in our own patients with the reports in the literature.DESIGN Open prospective, uncontrolled administration of quinagolide in patients with BCR (defined for this report as failure to attain normal prolactin levels after 4 months of bromocriptine at maximum tolerated doses), or BCI (defined as a patient request to cease bromocriptine treatment because of side‐effects at doses that were required, or failed, to normalize PRL levels).MEASUREMENTS Prolactin levels, menses or pregnancy, and side‐effects.PATIENTS Six with BCR, and six with BCI (microprolactinoma in 7, macroprolactinoma in 5), treated with quinagolide 75 μg nightly increasing incrementally to a maximum of 450 μg. One patient who had taken part in a multicentre study of quinagolide in macroprolactinomas had BCI, and 11 further patients in the endocrine clinic who had BCR or BCI were offered quinagolide therapy under named‐patient compassionate arrangements.RESULTS Normal prolactin in 4/5 with BCR (3/6 with side‐effects, none of them quinagolide intolerant), and normal prolactin in 2/6 with BCI (4/6 with side‐effects, two of them quinagolide intolerant).CONCLUSIONS Results in our 12 patients are broadly in line with those in 51 patients with bromocriptine resistance and 39 with bromocriptine intolerance extracted from various published reports, which together suggest that prolactin can be normalized in 16% of patients with bromocriptine resistance by quinagolide in doses of 225 μg or less, and in a further 20% by higher doses up to 600 μg. in bromocriptine intolerance, prolactin was normalized by quinagolide in doses of 225 μg or less In 58% of published cases and in 3 more patients by higher doses up to 1050 μg. About half the patients with bromocriptine resistance or bromocriptine intolerance who are treated with quinagolide experience side‐effects, and around 7% are quinagolide Intolerant. Doses need not exceed 225 μg, until failure to respond at this dose level is demonstrated.
Adrenocorticotrophin‐independent unilateral macronodular adrenal hyperplasia occurring with myelolipoma: an unusual cause of Cushing's syndrome
Authors: Jenkins P. J. , Chew S. L. , Lowe D. G. , Reznek R. H. , Wass J. A. H. 
Published: March 2008

SummaryWe report a case of Cushing's syndrome due to ACTH‐independent unilateral macronodular adrenal hyperplasia that occurred with a myelolipoma and propose that these two entitles may be linked to the production of an adrenal growth factor.
Primary hyperparathyroidism masked by antituberculous therapy‐induced vitamin D deficiency
Authors: Kovacs Christopher S. , Jones Gienviiie , Yendt Edmund R. 
Published: March 2008

SummaryAntituberculous chemotherapy agents, particularly rif‐ampicin and isoniazid, affect vitamin D metabolism and can create biochemical evidence of vitamin D deficiency. Vitamin D deficiency induces a state of resistance to parathyroid‐ hormone. This study sought to explain the temporary resolution of hypercalcaemia and hyper‐calciuria, during antituberculous chemotherapy with rifampicin and isonizid, in a subject with a surgically proven parathyroid adenoma and coincidental spinal tuberculosis. Serum ionized calcium, 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D, plasma Parathyroid hormone, and 24‐hour urine excretions of calcium, inorganic phosphorus and hydroxyproline were sequentially measured over a 3‐year interval that included 18 months of antituberculous chemotherapy. Initial serum Ionized calcium was 152mmol/l (normal 1·20‐1·35 mmol/l), 24‐hour urine calcium excretion was 9·40 mmol/day (normal 1·25 to 7·50 mmol/day) and plasma intact PTH was 9·2pmol/l (normal 0·0–4·5 pmol/l). During antitubercuious chemotherapy the serum ionized calcium and 24 hour urine calcium excretion were normal but the plasma PTH rose to higher levels. Following completion of the chemotherapy, hypercalcaemia and hypercalciuria returned with levels similar to those observed pretreatment. Serum 25‐hydroxyvltamin D was low at 8·25 nmol/l (normal 20 to 90 nmol/l) during antituberculous chemotherapy, but was normal before and after. Serum 1,25‐dihydroxyvltamin D was normal throughout the 3‐year Interval. We conclude that the antituberculous chemotherapy induced relative vitamin D deficiency and resistance to parathyroid hormone action, thereby masking the hyperparathyroidism and hypercalcaemia until the chemotherapy was completed.
The effect of pharmacological dosages of glucocorticoids on free living total energy expenditure in man
Authors: Chong P. K. K. , Jung R. T. , Scrimgeour C. M. , Rennie M. J. 
Published: March 2008

SUMMARYOBJECTIVES Weight gain had previously been thought to be due to increased calorie intake alone though no information on its effect on total energy expenditure is available in humans. We therefore assessed whether weight gain associated with glucocorticoids is due to a reduction in energy expenditure.DESIGN We performed an open study with 1 mg of betamethasone given orally twice a day for 21 days.SUBJECTS Seven healthy female volunteers, age range 26–55 years, body mass index 19 to 40, mean 27 kg/m2.MEASUREMENTS Total free living energy expenditure was measured by the doubly labelled water method (D218O), resting metabolic rate by ventilated hood indirect calorimetry and fat free mass from the dilution volume of oxygen‐18 labelled water. Body composition and components of energy expenditure were assessed before and during the final 14 days of betamethasone administration.RESULTS Weight increased by a mean of 1·2 kg (P < 0·05) because of a significant rise in fat mass (1·5 kg) with no change in fat free mass. Resting metabolic rate remained unaltered on betamethasone but total energy expenditure increased in all subjects with a significant mean rise of 26% from 11·7 to 14·7 MJ/24 h (P < 0·05). The energy component of physical activity with thermogenesis increased on average 52% (from 5·8 to 8·9 MJ/24 h; P < 0·05). The rise in energy expenditure was still apparent after correction for the increase in body weight. Fasting respiratory quotient (RQ) increased from 0·81 to 0·86 with no change in fasting blood glucose. Betamethasone did not result in an energy sparing effect on the two components of energy expenditure studied.CONCLUSIONS Body weight increased on betamethasone entirely due to an increase in fat mass. This occurred despite a rise in total energy expenditure which involved specifically that component accounted for by physical activity plus thermogenesis. The most likely explanation is that betamethasone increased dietary energy intake significantly in excess of expenditure. We estimate that an average extra energy intake of 2·8 MJ/day would have had to be consumed for this rise in fat mass to occur even before taking into account the energy intake cost of the rise in expenditure.
The overnight single‐dose metyrapone test is a simple and reliable index of the hypothalamic‐pituitary‐adrenal axis
Authors: Fiad Tarek M. , Kirby John M. , Cunningham Sean K. , McKenna T. Joseph 
Published: March 2008

OBJECTIVES The ACTH stimulation test examines adrenal responsiveness but may not examine the entire hypothalamic‐pituitary‐adrenal (HPA) axis and requires parenteral administration. The cortisol response to hypoglycaemia provides an index of activity of the entire HPA axis but is demanding for patients and medical staff. The aim of the present study was to examine the performance of the overnight single‐dose metyrapone test as it provides a simple alternative test for HPA axis function.DESIGN Audit of the overnight metyrapone test performed in one centre between 1979 and 1991.PATIENTS Three hundred and ninety‐eight patients underwent 576 tests. Comparisons between the responses to metyrapone and the ACTH stimulation test and of the responses to metyrapone and insulin induced hypoglycaemia test were possible in 87 and 17 patients respectively.MEASUREMENTS Following the midnight administration of metyrapone tablets, 30 mg/kg orally, blood samples were obtained between 0800 and 0930 h for radioimmunoassay of both 11‐deoxycortisol and cortisol.RESULTS Five hundred and seventy‐six metyrapone tests were performed on 398 patients with no serious side‐effects encountered. Andrenal insufficiency was diagnosed in 105 patients. Of these, 18 had a primary adrenal disorder and 87 had a disorder of the hypothalamic‐pituitary unit. One hundred per cent concordance between the metyrapone, the ACTH and the hypoglycaemia test was seen in patients with primary adrenal insufficiency. In 19 patients with secondary adrenal insufficiency, who underwent both the metyrapone and the ACTH tests, discord between these two tests was observed in 10 patients (53%). Nine of these patients demonstrated a normal response to ACTH and a subnormal response to metyrapone. In only one patient was an abnormal cortisol response to ACTH associated with a normal response to metyrapone. In contrast, in 17 patients discord between the metyrapone and the hypoglycaemia test was seen in only 1 patient who demonstrated a normal response to the metyrapone test and a subnormal response to hypoglycaemia.CONCLUSION Since the metyrapone test gives similar information about hypothalamic‐pituitary axis function as does the hypoglycaemia test, we recommend the use of the overnight metyrapone test as a safe, simple and reliable index of the hypothalamic‐pituitary axis integrity. The ACTH stimulation test should not be used for patients suspected of having secondary adrenal insufficiency.
Menstrual disturbances in thyrotoxicosis *
Authors: Krassas G. E. , Pontikides N. , Kaltsas Th. , Papadopoulou Ph. , Batrinos M. 
Published: March 2008

OBJECTIVES In thyroid textbooks it is stated that hyperthyroidism in women may be associated in almost 50% of the cases with hypomenorrhoea, oligomenorrhoea or amenorrhoea and perhaps with reduced fertility. Our experience at a busy thyroid clinic has given a picture which differs from that described in the literature. Most of our female thyrotoxic patients had normal menstruation. This study was performed to define the menstrual abnormalities in hyperthyroidism.DESIGN AND PATIENTS We investigated the menstrual history, starting 6 months before the discovery of the disease, the smoking habits and the body mass index (BMI), in 214 female, premenopausal thyrotoxic patients and a similar number of normal controls matched for age and weight.MEASUREMENTS TT4 and TT3 were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2.RESULTS Of the 214 patients, 168 (78·5%) had regular menstrual cycles and 46 (21·5%) irregular cycles. No difference in BMI was found between the patients with or without menstrual abnormalities. Out of the 46 patients with irregular periods, 23 (50%) were smokers, while only 32 out of the 168 patients (19%) with normal periods were smokers (P < 0·001). TT4 levels were higher as a group in patients with menstrual disturbances (mean±SD 267·7 ± 66·9 nmol/1) than in those with normal periods (240·6 ± 47·6 nmol/1) (P < 0·05). The 23 smokers with irregular periods had higher TT4 levels (280·5 ± 51·8 nmol/1) than the remaining non‐smokers from the same group (241·9 ± 43·7 nmol/1) (P < 0·01). No such differences were found for TT3 levels. Out of 214 normal controls, matched for age and weight, 196 (91·6%) had normal menstruation and 18 (8·4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. Out of 18 normal controls with irregular periods, 6 (33·3%) were smokers, while 57 (29·1%) out of 196 with normal periods were smokers.CONCLUSIONS These data demonstrate that hyperthyroidism in women is less frequently associated with menstrual abnormalities than was previously believed. Furthermore, no patient presented with amenorrhoea. Smoking and TT4 levels are strongly associated with the occurrence of menstrual disturbances in thyrotoxicosis.
Biochemical markers of bone turnover in girls during puberty
Authors: Blumsohn A. , Hannon R. A. , Wrate R. , Barton J. , AI‐Dehaimi A. W. , Colwell A. , Eastell R. 
Published: March 2008

OBJECTIVES Bone turnover and the rate of bone growth increase dramatically during puberty. A number of new assays for the estimation of bone resorption and formation rates have been developed over recent years, and puberty acts as a convenient model for evaluation of these measurements. The aim of this study was to explore the interrelationships between pubertal development, biochemical markers of bone turnover, Insulin‐like growth factor I and oestradiol in healthy pubertal girls.SUBJECTS Ninety‐one healthy girls (ages 11·6–15·5 years) were studied. All subjects were apparently healthy, and were not taking medications known to influence calcium homeostasls. Breast examination was performed to assess pubertal stage according to Tanner. The adult reference range for biochemical markers of bone turnover was obtained from concurrent studies on 42 healthy premenopausal women ranging in age between 20 and 45 years.DESIGN AND MEASUREMENTS Blood samples were obtained from subjects between 0800 and 1000 h. Urine samples were collected between 1330 and 1600 h. We measured total and bone specific alkaline phosphatase, osteocalcin, and type I procollagen carboxyterminal pro‐peptide as markers of bone formation. Tartrate resistant acid phosphatase, carboxyterminal pyridinoline cross‐linked telopeptide, creatinine corrected urinary deoxypyr‐Idlnoline, immunoreactive urinary pyrldinolines, and urinary galactosyl hydroxylysine were measured as markers of bone resorption.RESULTS Bone turnover as reflected by each of the markers was maximal in mid puberty (breast Tanner stages II and III) and decreased towards adult levels in late puberty (P< 0·001). However, the magnitude of the mid‐pubertal increase differed between markers. In particular, the pubertal increase In levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline were higher than the Increase shown by the other markers. All markers were significantly lower after the menarche. Circulating insulin‐like growth factor I and Insulin like growth factor binding protein‐3 were not important determinants of pubertal changes In bone turnover. In contrast, there was a significant negative correlation between oestradiol and all markers of bone formation and resorption during puberty.CONCLUSIONS The greater pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline suggests that these markers may be relatively more sensitive as indicators of skeletal health during puberty. The differences between markers may reflect differences in the bone specificity of the analytes, or differing mechanisms of production and clearance. The negative correlation between oestradiol and markers of bone resorption and formation suggests that this hormone may be responsible for the reduction in bone turnover in late puberty.
Continuous combined oestrogen/progestin therapy is well tolerated and increases bone density at the hip and spine in post‐menopausal osteoporosis
Authors: Grey Andrew B. , Cundy Tim F. , Reid Ian R. 
Published: March 2008

OBJECTIVES Although oestrogen/progestin therapy is effective prophylaxis against post‐menopausal osteoporosis, its efficacy in the treatment of established disease is uncertain. In addition, cyclical oestrogen/progestin regimens are associated with low rates of patient acceptance. The present study assesses the acceptability of, and skeletal response to, continuous combined hormone replacement therapy in osteoporotic late post‐menopausal women.DESIGN Retrospective, controlled study.PATIENTS One hundred and four osteoporotic late postmenopausal women treated with continuous combined hormone replacement therapy (5 mg medroxyprogester‐one acetate daily and either 0·625 mg oral conjugated oestrogens or 50 μg transdermal oestradiol daily) were followed for an average of 1 year (range 2–38 months). Control subjects were 19 healthy normal women matched for menopausal age and weight.MEASUREMENTS Adverse effects and compliance rate were monitored. Baseline and 1‐year measurements of lumbar spine bone mineral density (BMD) were performed using dual‐energy X‐ray absorptiometry in 51 women, 22 of whom also had measurements at 2 years. Twenty‐eight women had proximal femur scans at baseline and 1 year.RESULTS Eighty‐six per cent of women continued to take continuous combined hormone replacement therapy at the end of follow‐up. Mastalgia (44%) and vaginal bleeding (29%), the most common side‐effects, were minor and self‐limiting in virtually all women. Spinal BMD increased by 7·1 ± 0·8% (mean±SEM P < 0·001) at 1 year and by 8·9 ± 1·5% (P < 0·001) at 2 years. In the proximal femur, BMD increased by 2·9 ± 0·9% at the femoral neck (P= 0·01) and by 2·5±0·9% (P= 0·001) at the trochanter at 1 year. BMD tended to decline in the control group. Among the women taking hormone replacement therapy, the increase in spinal BMD was similar in those treated with 0·3–0·44 mg/day of conjugated equine oestrogens to those receiving 0·45–0·625 mg/day.CONCLUSION Continuous combined hormone replacement therapy is an acceptable therapy to osteoporotic late post‐menopausal women and produces substantial increases in lumbar spine and proximal femoral bone mineral density.
Expression and processing of parathyroid hormone‐related protein in a pancreatic endocrine cell tumour associated with hypercalcaemia
Authors: Ratcliffe W. A. , Bowden S. J. , Dunnet F. P. , Hughes S. , Emly J. F. , Baker J. T. , Pye J. K. , Williams C. P. 
Published: March 2008

SUMMARYWe describe a patient with a neuroendocrine tumour of the pancreas associated with hypercalcaemia which was attributed to production of parathyroid hormone‐related protein (PTHrP) by the tumour. Plasma PTHrP 1–86 was significantly raised, and fell following surgical resection of the tumour. PTHrP mRNA and peptide were identified in tumour tissue by in‐situ hybridization and immunohisto‐chemistry respectively. PTHrP was quantitated in an extract of tumour tissue by three region‐specific immunoassays (PTHrP 1–34 45.2 pmol/g, PTHrP 37–67 81.7 pmol/g, PTHrP 1–86 27.3 pmol/g) and suggested the presence of excess of amino‐terminal and mid‐region immunoreactivity. On chromatography of the tumour extract the first peak eluted as 22 kDa and comprised approximately equimolar 1–34, 37–67 and 1–86 activities. The second and major peak of 16 kDa contained only 37–67 activity, while the third peak of 6 kDa contained only 1–34 activity. This suggested that the tumour contained a native or intact form of PTHrP together with two major subfragments containing 37–67 and 1–34 activity respectively. Thus chromatographic separation and quantitation of PTHrP by region‐specific immunoassays have provided new information on in‐vivo proteolytic processing by tumour tissue by indicating that a site of cleavage is located between residues 17 and 61. Our findings are compatible with cleavage at residue 37, a site previously indicated from in‐vitro studies.