bluuebunny/crossref_metadata_2025_split huggingface dataset:
α2‐adrenoceptor regulation of the hypothalamic‐pituitary‐adrenocortical axis in obesity
Authors: Pasquali Renato , Vicennati Vaientina , Calzoni Fabio , Gnudi Umberto , Gambineri Alessandra , Ceroni Luana , Cortelli Pietro , Menozzi Renata , Sinisi Rosa , Del Rio Grariano 
Published: March 2003

SummaryBACKGROUND Abdominal obesity is associated with hyper‐responsiveness of the hypothalamic‐pituitary‐adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via α‐adrenoceptor modulation.DESIGN In this study, we investigated the effects of pre‐treatment with an α2‐adrenoceptor agonist, clonidine (2μg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0.001 mg/ kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100μg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A‐BFD) or peripheral (P‐BFD) body fat distribution and in nonobese controls.RESULTS During the control CRH+AVP test the ACTH but not the cortisol response was higher (P<0.05) in obese A‐BFD women than In controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadlly and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A‐BFD group significantly (P<0.05) more than in the P‐BFD group.CONCLUSIONS This study shows that α2‐adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH+AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.
CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas
Authors: Leong King S. , Foy Patrick M. , Swift Andrew C. , Atkin Steve L. , Hadden David R. , MacFarlane Ian A. 
Published: March 2003

OBJECTIVEThe management of CSF rhinorrhoea following dopamine agonist (DA) treatment for invasive prolactinomas is difficult and there is no clear consensus for its treatment. Our objective was therefore to investigate the different treatments for this condition.DESIGN AND PATIENTSWe examined the case notes of five patients with invasive prolactinomas and CSF rhinorrhoea following DA treatment. The different ways in which this complication had been managed is detailed along with a review of the literature.RESULTSFive patients aged 24–67 years (3 male) with massive invasive prolactinomas (serum prolactin 95000–500000 mU/l) eroding the skull base were treated with dopamine agonists (3 bromocriptine, 1 cabergoline and 1 both). CSF rhinorrhoea developed in all patients between 1 week and 4 months after commencing dopamine agonist treatment. In two patients (cases 1 and 4), CSF rhinorrhoea ceased within a few days of stopping bromocriptine but restarted when treatment was resumed. One of these (case 4), a 67‐year‐old woman had no further treatment and CSF leakage stopped completely. She died of unrelated medical problems 3 years later. In one patient staphylococcus aureus meningitis and pneumocephalus developed as a complication of CSF rhinorrhoea. Three patients had endoscopic nasal surgery to repair the fistula using muscle grafts, and to decompress the pituitary tumour, with success in two. One patient had intracranial surgery and dural repair, which was successful in sealing the leak.CONCLUSIONSWe suggest that surgery as soon as is feasible is the treatment of choice for the repair of a CSF leak following dopamine agonist treatment. An additional strategy is the withdrawal of dopamine agonist to allow tumour re‐growth to stop the leak.
Clinical features and pathogenesis of thyrotoxicosis in adult Melanesians in Papua New Guinea
Authors: Michelangeli  , Pawape  , Sinha  , Ongugu  , Linge  , Sengupta B  , Tait  , Colman  
Published: March 2003

OBJECTIVETo investigate the cause of an apparent increase in the incidence of thyrotoxicosis in the Melanesian population of the coastal areas around Port Moresby, Papua New Guinea.DESIGNConsecutive patients attending the thyroid clinic at Port Moresby General Hospital were included in the study which collected clinical and immunogenetic data.PATIENTSOne hundred and ninety‐four patients with thyrotoxicosis were studied. The mean age was 31 years. The clinical features were typical for thyrotoxicosis apart from increased pigmentation, which occurred in the majority of patients and which reversed with treatment with antithyroid drugs and resolution of the thyrotoxicosis.MEASUREMENTSAntibodies to thyroid peroxidase, thyroglobulin and the thyrotropin receptor were present in 99%, 52% and 69% of patients, respectively, confirming that all cases were caused by autoimmune thyroid disease. Fine needle aspirations in 42 of 43 patients were consistent with Graves' disease.CONCLUSIONSThe cause of this apparent sudden increase in Graves' disease in the coastal region around Port Moresby, an apparently iodine‐replete area, remains unexplained.
Insulin sensitivity and secretion influence the relationship between growth hormone‐binding‐protein and leptin
Authors: Fernandez‐Real José‐Manuel , Granada Maria Luisa , Ruzafa Ana , Casamitjana Roser , Ricart Wifredo 
Published: March 2003

BACKGROUNDA direct relationship between body mass index (BMI), visceral adipose tissue, insulin levels and growth hormone‐binding protein (GHBP) activity has consistently been reported. It was recently described that GHBP directly depends on serum leptin levels. Since leptin co‐varies with insulin secretion and/or sensitivity, we aimed to study the influence of these variables on plasma GHBP activity.SUBJECTSIn order to isolate the effects of obesity per se from those of insulin secretion, three groups of subjects were prospectively studied: 14 lean, 10 obese and nine obese subjects with glucose intolerance.MEASUREMENTSThe percentage of body fat was measured through bioelectric impedance. Insulin sensitivity and secretion were determined through a frequently sampled intravenous glucose tolerance test with minimal model analysis. Serum leptin was measured by radioimmunoassay. GHBP activity was determined by the high performance liquid chromatography‐gel filtration method.RESULTSPlasma GHBP activity was found to correlate with BMI (r = 0.65, P < 0.0001), fat mass (r = 0.51, P = 0.003), waist circumference (r = 0.64, P < 0.0001), waist‐to‐hip ratio (r = 0.42, P = 0.01), insulin sensitivity (SI, r = − 0.61, P = 0.0001), insulin secretion (expressed as the acute insulin response to intravenous glucose, AIRg) (r = 0.48, P = 0.006) and leptin concentration (r = 0.49, P = 0.004). The associations with SI (r = − 0.42, P = 0.02) and AIRg (r = 0.38, P = 0.03) persisted even after controlling for fat mass. Since insulin secretion and insulin sensitivity usually covary in glucose tolerant subjects (an increased insulin secretion is necessary to compensate a decreased insulin sensitivity), we constructed a multiple linear regression to predict GHBP activity. In this model, SI (P = 0.005), AIRg (P = 0.02) and SD score‐leptin (P = 0.03) independently contributed to 34, 10 and 8% of the variability in serum GHBP activity.CONCLUSIONSOur results suggest that plasma GHBP activity is simultaneouslly influenced by insulin secretion and sensitivity and leptin. Perhaps leptin, through increased insulin secretion, might induce GHBP/GH secretion, explaining the normal to high insulin‐like growth factor (IGF)‐I levels found in overnutrition.
Administration of recombinant human growth hormone on alternate days is sufficient to increase whole body protein synthesis and lipolysis in growth hormone deficient adults
Authors: Lucidi Paola , Laureti Stefano , Santoni Stefania , Lauteri Marco , Busciantella‐Ricci  , Angeletti Gabriella , Santeusanio Fausto , De Feo Pierpaolo 
Published: March 2003

OBJECTIVEAt present, the duration of the effect of recombinant human growth hormone (rhGH) on the rates of protein synthesis and lipolysis in GH deficient (GHD) adults is unknown. This study was designed to establish the frequency of rhGH administration necessary to provide the beneficial metabolic effects of the hormone in GHD adults.DESIGN AND PATIENTSTwo different studies (A and B) were performed in two groups of five GHD men. In study A, whole body protein and lipid kinetics was determined in the basal state (Bas), 12 (GH12h) and 36 (GH36h) h after the last of seven injections of rhGH (3.3 μg/kg), given at bedtime on alternate days. In study B, the same parameters were determined in the basal state (Bas), 60 (GH60h) and 84 (GH84h) h after the last of seven injections of rhGH (3.3 μg/kg), given at bedtime at 3 day intervals.MEASUREMENTSThe rates of protein metabolism were estimated by infusing [1–13C]leucine, and those of lipolysis by infusing [1,1,2,3,3‐D5]glycerol.RESULTSLeucine oxidation decreased (P < 0.01) by approximately 30% after GH12h and GH36h but did not change after GH60h and GH84h. Non‐oxidative leucine disposal increased after GH12h and GH36h by approximately 13% (P < 0.05) whereas it did not change after GH60h and GH84h. Glycerol appearance increased (P < 0.01) by approximately 45% after GH12h and GH36h but did not change after GH60h and GH84h.CONCLUSIONSThe effects on protein and lipid metabolism following the injection of rhGH last longer than 36 and less than 60 h. In fact, rhGH administration on alternate days induced a sustained increase in the rates of protein synthesis and lipolysis of GHD adults, whereas a longer interval of administration (3 days) had no effect by 60 h.
Testicular dysfunction in men with primary hypothyroidism; reversal of hypogonadotrophic hypogonadism with replacement thyroxine
Authors: Donnelly Peter , White Christopher 
Published: March 2003

OBJECTIVEPrimary hypothyroidism can cause disturbances in normal gonadal function. The aim of this study was to investigate the relationship in men between hypogonadism and primary hypothyroidism and the extent to which free and total testosterone levels rose after introduction of replacement thyroxine.DESIGNPaired study of patients in a hypothyroid and thyroxine treated state.PATIENTSTen men with primary hypothyroidism.MEASUREMENTSFree and total testosterone, gonadotrophin and prolactin levels before and after thyroxine replacement therapy.RESULTSLow free testosterone levels (161 ± 62 pmol/l) demonstrated at the time the men were hypothyroid rose significantly with the commencement of thyroxine replacement (315 ± 141 pmol/l; P < 0.001). Gonadotrophin levels were not elevated consistent with hypogonadotrophic hypogonadism. Hyperprolactinaemia, which can occur in primary hypothyroidism and cause hypogonadotrophic hypogonadism, was not present in the majority of these patients. However a reduction in prolactin level was evident with thyroxine replacement and a rise in free testosterone levels.CONCLUSIONThis suggests an effect of hypothyroidism on gonadotrophin secretion at the level of the hypothalamus‐pituitary, either directly or through modulation of prolactin secretion. Low free testosterone may also be a contributing factor to some of the symptoms and signs of hypothyroidism in men.
Relapse of hirsutism following long‐term successful treatment with oestrogen–progestogen combination
Authors: Kokaly Waleed , McKenna T. Joseph 
Published: March 2003

OBJECTIVEWhile several forms of treatment have been reported to be successful in relieving hirsutism over periods of 6–12 months, there is little if any information on the long‐term outcome of hirsutism following the withdrawal of successful treatment. The combination of ethinyl oestradiol, 35 μg, and cyproterone acetate, 2 mg (EE‐CA) for 21 days followed by 7 days without treatment is widely used in a cyclical manner in the treatment of hirsutism. The present study was undertaken to evaluate the outcome of withdrawal of long‐term successful treatment of hirsutism with EE‐CA.DESIGN, PATIENTS AND MEASUREMENTIn this retrospective study the clinical records of 57 patients with idiopathic hirsutism or polycystic ovary syndrome who had been treated with EE‐CA were reviewed. The degree of hirsutism had been assessed by the Ferriman and Gallwey scoring system (FG). The testosterone/sex hormone binding globulin ratio (T/SHBG), was derived prior to and following the introduction of treatment with EE‐CA.RESULTSFifty‐two of the 57 patients achieved a satisfactory clinical response. In the group of patients who were satisfied with the outcome of treatment, FG decreased from 12.9 ± 3.6 to 5.5 ± 2.5 and T/SHBG ratio decreased from 11.3 ± 9.5 to 1 ± 0.8 (reference range: 1–5.2). The duration of treatment prior to its withdrawal in this group was 28.2 ± 13.7 months. The five patients who were not satisfied with the response abandoned treatment after 16 ± 2.8 months; the pretreatment FG was 16.2 ± 8.3, while the T/SHBG decreased from 6.1 ± 3.1 to 1.1 ± 0.6 in these patients. Subsequent follow‐up data, after withdrawal of treatment, were available on 34 of these 52 patients. Twenty‐eight of the 34 patients exhibited relapse of hirsutism after 6.15 ± 2.8 months. Six patients did not relapse during a follow‐up period of 18.8 ± 7.8 months. The six patients who did not relapse were treated for a significantly longer period than the group who relapsed, 40 ± 6.9 and 26.1 ± 8.3 months, respectively, P < 0.01. However, the groups did not differ significantly when examined for pretreatment FG, 11.5 ± 3.8 and 13.2 ± 3.6 and pretreatment T/SHBG 8.9 ± 5 and 13.4 ± 11.9.CONCLUSIONThese data indicate that ethinyl oestradiol and cyproterone acetate achieved a satisfactory clinical outcome in the treatment of hirsutism in 90% of patients. However, on withdrawal of treatment after a mean duration of over 2 years, relapse occurred in 80% of these patients after a mean of 6 months. If it is assumed that the successfully treated patients lost to follow‐up all maintained long‐term remission, the relapse rate is still an unsatisfactory 65% at 6 months. These are disappointing results which indicate for the first time that successful outcome requires that treatment be maintained for several years. Patients embarking upon treatment for hirsutism should be advised that maintenance of reduced hair growth requires long‐term treatment, probably for at least 3–4 years.
One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults
Authors: Beentjes John A. M. , van Gorkom Britta A. P. , Sluiter Wim J. , de Vries Elisabeth G. E. , Kleibeuker Jan H. , Dullaart Robin P. F. 
Published: March 2003

SummaryOBJECTIVE Increased colonic epithelial cell proliferation has been found in various conditions associated with increased risk of colorectal cancer including acromegaly. In a placebo‐controlled study we determined the effect of growth hormone (GH) replacement therapy in GH deficient adults on the colonic epithelial proliferation rate.PATIENTS AND DESIGN Sixteen GH deficient adults were randomised to low dose GH therapy (1 U (0.5 mg) subcutaneously per day, n=5), high dose GH therapy (2U daily, n=5) or placebo (n= 6) during 6 months. Thereafter, all patients were treated with 2U of GH daily during a 6‐months open extension period.MEASUREMENTS Plasma Insulin‐like growth hormone I (IGF‐I) and IGF binding protein 3 (IGF BP3) concentrations were measured using commercial RIA kits. The colonic epithelial proliferation rate, expressed as overall crypt labelling index (LI) using 5‐bromo‐2′‐deoxyuridine (BrdU) immunostaining, was determined at baseline, after 6 months treatment and at the end of the 6 months open extension period.RESULTS IGF‐I rose from 8.9±6.7 to 34.6 ±20.0 nmol/l after 6 months in 8 GH treated patients (P <0.01 from baseline; P<0.01 from change with placebo). In the extension study, plasma IGF‐I was also increased in the patients who previously received placebo (P<0.02, n=5). LI was evaluable in 14 biopsies at baseline, in 16 after 6 months and in 14 after 12 months. Overall crypt LI did not change in 8 GH treated patients after 6 months (P< 0.40 from baseline; P>0.80 from change with placebo). In the extension study, overall crypt LI was also unchanged in those patients who received GH after placebo (n= 5, P>0.40) and in those who continued GH replacement (n=9, P>0.60; P>0.80 from change in initially placebo treated patients). Separate evaluation of the LI at the basal, mid and luminal portions of the colonic crypts also did not reveal any effect of GH treatment on BrdU labelling.CONCLUSIONS Six to 12 months of GH replacement therapy, aimed to increase plasma IGF‐l into the (high) physiological range, does not adversely affect colonic epithelial cell proliferation as a biomarker for the risk of development of colorectal cancer.
Cardiovascular disease in women with polycystic ovary syndrome at long‐term follow‐up: a retrospective cohort study
Authors: Wild Sarah , Pierpoint Tracey , McKeigue Paul , Jacobs Howard 
Published: March 2003

OBJECTIVEPolycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle‐aged women previously diagnosed with PCOS and age‐matched control women.DESIGNA retrospective cohort study of women diagnosed with PCOS in the United Kingdom before 1979.PATIENTSSeventy cohort members died before 31 March 1999. Morbidity data were collected from 319 women with PCOS and 1060 age‐matched control women. Sixty‐one women with PCOS and 63 control women attended a clinical examination.MEASUREMENTSData were collected from death certificates, general practitioners' records and questionnaires with measurement of cardiovascular risk factors in a subsample of questionnaire respondents.RESULTSAll‐cause and cardiovascular mortality in the cohort were similar to women in the general population (standardized mortality ratios (95% CI): 93 (72–117) and 78 (45–124), respectively). Women with PCOS had higher levels of several cardiovascular risk factors: diabetes (P = 0.002) hypertension (P = 0.04), hypercholesterolaemia (P < 0.001), hypertriglyceridaemia (P = 0.02) and increased waist:hip ratio (P = 0.004). After adjustment for BMI, odds ratios (OR) were 2.2 (0.9–5.2) for diabetes, 1.4 (0.9–2.0) for hypertension and 3.2 (1.7–6.0) for hypercholesterolaemia. A history of coronary heart disease (CHD) was not significantly more common in women with PCOS (crude OR (95%CI) 1.5 (0.7–2.9)) but the crude OR for cerebrovascular disease was 2.8 (1.1–7.1).CONCLUSIONAt long‐term follow‐up, a history of nonfatal cerebrovascular disease and cardiovascular risk factors including diabetes are more prevalent among women with polycystic ovary syndrome. Morbidity and mortality from of coronary heart disease among women with polycystic ovary syndrome is not as high as previously predicted. This finding challenges our understanding of the aetiology of coronary heart disease in women.
Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo‐controlled feasability study for male contraception
Authors: Kamischke Axel , Plöger Daniela , Venherm Stefan , Von Eckardstein Sigrid , Von Eckardstein Arnold , Nieschlag Eberhard 
Published: March 2003

OBJECTIVEApproaches to hormonal male contraception are based on injectable testosterone esters alone or in combination with gestagens or GnRH analogs but the short half‐life of clinically used testosterone esters have long hindered further development. This study was designed to prove the efficacy of the long‐acting testosterone undecanoate ester (TU) alone or in combination with oral levonorgestrel (LNG) in a phase II clinical trial.DESIGN AND SUBJECTSTwenty‐eight healthy men were randomized to receive injections of 1000 mg TU every 6 weeks in combination with daily oral LNG (250 μg) or daily oral placebo treatment over a period of 24 weeks, followed by a control period of 28 weeks.MEASUREMENTSDuring the course of the study semen analysis, reproductive hormone analysis, analysis of clinical chemistry and lipid parameters, well‐being and sexual function, sonography of scrotal contents and prostate were performed.RESULTSMarked suppression of gonadotrophins in both treatment groups resulted in azoospermia in 8/14 and 7/14 volunteers and severe oligozoospermia (< 3 × 1012/l) in 4/14 and 7/14 in the placebo and gestagen treated groups, respectively. Time to induction of azoospermia (mean ± SEM) was not significantly different between the placebo (week 19.5 ± 2.2) and LNG groups (week 15.4 ± 2.2). During the whole treatment period mean testosterone serum concentrations remained within normal limits. Although not significant, it was evident that volunteers who became azoospermic had a better suppression of gonadotrophins and lower SHBG levels during treatment compared to non‐azoospermic volunteers. Despite better gonadotrophin suppression in the LNG group no significant differences compared to placebo could be observed in the extent and kinetics of suppression of spermatogenesis, thus not demonstrating a major beneficial effect of LNG in the combination with injectable TU. Treatment led in both groups to a decrease of HDL and Lp(a) which was more pronounced in the LNG group (P > 0.05).CONCLUSIONTreatment with 1000 mg testosterone undecanoate injected at 6 weekly intervals or in combination with levonorgestrel showed suppression of spermatogenesis comparable to weekly injections of 200 mg testosterone enanthate. Because of its long half‐life and in the absence of severe side‐effects, testosterone undecanoate can be considered as first choice testosterone ester in further studies of hormonal male contraception.