bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum leptin levels are higher but are not independently associated with severity or mortality in the multiple organ dysfunction/systemic inflammatory response syndrome: a matched case control and a longitudinal study
Authors: Papathanassoglou Elizabeth D. E. , Moynihan Jan A. , Ackerman Michael H. , Mantzoros Christos S. 
Published: March 2003

OBJECTIVEHypercatabolism and immune dysfunction are closely associated with the development of systemic inflammatory response–multiple organ dysfunction (SIRS/MODS) in critical illness. It remains unclear however, whether leptin, an adipocyte‐derived hormone whose levels are influenced by several cytokines and which regulates immune function, food‐intake and energy expenditure is independently related to the development of and/or severity and mortality from SIRS/MODS.DESIGN and PATIENTSTo assess the role of leptin in SIRS/MODS we performed a matched case control and a longitudinal study (14 days) in 35 critically ill patients with SIRS/MODS and 35 matched controls.RESULTSBaseline leptin levels were positively associated with body mass index (BMI) and TNF‐α (P < 0·01) in patients and with IGF‐1 and IL‐6 levels (P < 0·05) in controls. Furthermore, leptin levels exhibited a progressive increase from the first to the last day of the study and although baseline levels were not different, peak leptin levels as well as leptin levels on the last day of the study were significantly higher in cases than in controls (P < 0·05). TNF‐α levels, IL‐6 and cortisol levels were also higher, whereas IGF‐1 levels were lower in cases (P < 0·05). To assess whether leptin levels are independently associated with SIRS/MODS we performed multivariate logistic regression analysis which revealed that leptin up‐regulation in cases is mediated by elevated TNF‐α and cortisol levels. Finally, there was no independent association between leptin and survival in this group of critically ill patients.CONCLUSIONWe conclude that cytokines and cortisol upregulate leptin levels, which may contribute to the development of the hypercatabolism, wasting and immune dysfunction but leptin levels are not independently associated with severity or mortality of patients with systemic inflammatory response–multiple organ dysfunction .
A critical examination of adrenal tuberculosis and a 28‐year autopsy experience of active tuberculosis
Authors: Lam King Yin , Lo Chung Yau 
Published: March 2003

OBJECTIVE Tuberculosis is potentially fatal and adrenal gland involvement is uncommonly reported. The aims of the current study were to define the characteristics of tuberculosis in hospitalized patients and to analyse the features of adrenal tuberculosis.DESIGN Retrospective analysis of autopsies and adrenalectomies.Patients 13 762 patients (13492 at autopsies and 270 at adrenalectomy).MEASUREMENTS The presence of active tuberculosis, the predisposing factors, the pathological features and organs of involvement were examined.RESULTS Active tuberculosis was present in 871 patients (6·5% of all 13492 autopsies). It was first diagnosed in 70% of these patients during autopsy. Cancers and a history of recent major operations were the 2 main concomitant factors in the patients with tuberculosis. Extra‐pulmonary tuberculosis was seen in 261 patients (30%). The five most common extra‐pulmonary sites of tuberculosis were the liver, spleen, kidney, bone and adrenal gland. Adrenal tuberculosis was seen in 52 of the 871 patients (6%) with active tuberculosis at autopsy and in 3 patients at adrenalectomy. The adrenal gland was the only organ involved by active tuberculosis in 14 of these 55 patients (25%; 35 men, 20 women). Tuberculosis was evident on macroscopic examination of the adrenal glands in 46% of the patients. On histological examination, caseous necrosis and granulomatous inflammation with Langhan's giant cells were seen in 71% and 40% of patients, respectively. Seven patients presented with signs and symptoms of Addison's disease due to bilateral adrenal involvement. Langhan's giant cells were frequently seen in histological sections and bilateral enlargement of the adrenal glands was often noted. Fine needle aspiration cytology was not useful for diagnosing adrenal tuberculosis.CONCLUSION Unexpected and extra‐pulmonary tuberculosis such as adrenal tuberculosis has been a common problem. A high index of suspicion, correct diagnosis and proper treatment are essential for the management of tuberculosis.
Elderly subjects show severe impairment of dehydroepiandrosterone sulphate and reduced sensitivity of cortisol and aldosterone response to the stimulatory effect of ACTH1−24
Authors: Giordano Roberta , Di Vito Lidia , Lanfranco Fabio , Broglio Fabio , Benso Andrea , Gianotti Laura , Grottoli Silvia , Ghigo Ezio , Arvat Emanuela 
Published: March 2003

OBJECTIVE Hyperactivity of the hypothalamic‐pituitary‐adrenal (HPA) axis in ageing has been reported both in humans and in animals and may be involved in age‐related changes in body composition, structure functions and metabolism, as well as in brain ageing. Despite the supposed HPA hyperactivity and its refractoriness to negative glucocorticoid feedback, low levels of dehydroepiandrosterone (DHEA) and its sulphate have been clearly demonstrated in human ageing and may suggest another cause of age‐related changes in structure function and metabolism. Thus, our aim was to verify the adrenal responsiveness to various ACTH doses in normal elderly subjects.DESIGN We studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of very low, low and supramaximal ACTH1−24 doses (0·06 µg or 0·5 µg followed by 250 µg ACTH1−24 i.v. at 0 and +60 minutes) in healthy elderly subjects (ES) [six females and two males, aged 63–75 years, body mass index (BMI) 22–26 kg/m2]. The results in ES were compared with those recorded in healthy young subjects (YS) (six females and six males, aged 22–34 years, BMI 20–25 kg/m2).RESULTS Basal DHEA levels in ES were lower (P < 0·05) than in YS, while F and A levels were similar in both groups. DHEA, F and A responses to ACTH were dose‐dependent in both groups. In ES, however, DHEA levels showed no response to the 0·06 µg dose, a modest increase after 0·5 µg and a clearer rise after 250 µg ACTH; at any dose, the DHEA response in ES was clearly lower than in YS (P < 0·04). The F responses to 0·5 µg and 250 µg ACTH in ES were similar to those in YS; whereas, in ES, 0·06 µg ACTH elicited a non significant F increase which was significantly lower than in YS (P < 0·05). Similarly, the A responses to the highest ACTH doses were similar in both groups but, in ES, 0·06 µg ACTH elicited no increase in A secretion, which was clearly lower than in YS (P < 0·03).CONCLUSIONS Normal elderly subjects show severe reduction of DHEA response to a wide range of ACTH doses, in agreement with peculiar impairment of the activity of the adrenal reticularis zone in ageing. In contrast to young adults, elderly subjects also show no cortisol and aldosterone response to a very low ACTH dose. This evidence indicates a reduced sensitivity to ACTH in the fasciculata and glomerulosa zones of the adrenal gland in ageing.
Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients
Authors: Minniti Giuseppe , Moroni Carlo , Jaffrain‐Rea Marie‐Lise , Esposito Vincenzo , Santoro Antonio , Affricano Cesare , Cantore Giampaolo , Tamburrano Guido , Cassone Rosario 
Published: March 2003

OBJECTIVE Transsphenoidal surgery results in biochemical remission of acromegaly in 45–80% of patients; however, few studies have addressed the impact of transsphenoidal surgery on cardiovascular function in acromegalic patients. The aim of this prospective study was to investigate the effects of postoperative GH/IGF‐I normalization on echocardiographic parameters and blood pressure (BP) in a series of patients with active acromegaly.DESIGN An open prospective study.PATIENTS Thirty newly diagnosed acromegalic patients undergoing transsphenoidal surgery.MEASUREMENTS Doppler echocardiography and 24‐h ambulatory blood pressure monitoring were performed before and 6 months after transsphenoidal surgery.RESULTS Fifteen patients were considered to be well controlled postoperatively (group A), as defined by normal age‐corrected IGF‐I levels and glucose‐suppressed GH levels less than 2 mU/l, the remaining 15 patients being considered as poorly controlled (group B). In group A, a postoperative decrease of left ventricular mass index was observed (104·4 ± 6·6 vs. 127·1 ± 7·7 g/m2; P < 0·001), associated with an improvement of some indices of diastolic function, such as an increase of the early/late transmitral peak flow velocity (P < 0·05) and a decrease of isovolumic relaxation time (P < 0·01). No significant change was observed in group B. A significant decrease of 24‐h systolic BP was also observed in group A (P < 0·05) and five of six patients normalized their BP circadian rythm. In contrast, a nonsignificant increase in BP values, with a persistent blunted BP profile where present, was observed in group B.CONCLUSIONS We conclude that successful transsphenoidal surgery is able to induce a significant improvement in some cardiac parameters and a slight reduction in systolic blood pressure in acromegalic patients.
Influence of implantation site and track geometry on the extrusion rate and pharmacology of testosterone implants
Authors: Kelleher S. , Conway A. J. , Handelsman D. J. 
Published: March 2003

BACKGROUND Implantation of testosterone pellets under the lateral abdominal wall skin is an old but popular and effective form of androgen replacement therapy. Extrusion of one or more pellets remains the most frequent adverse event.OBJECTIVE To determine whether an alternative implantation site (hip) and/or track geometry (two vs. four tracks) would reduce extrusion rates compared with the standard of a four‐track abdominal site. Additionally, the study aimed to evaluate the effects of site and track geometry on other adverse effects (bruising, infection) and the pharmacology of testosterone release from the implants.DESIGN A prospective, parallel‐group unmasked study design in a single centre. The primary objective was to evaluate sites, with evaluation of track geometry a subordinate objective made necessary by anatomical differences. Accordingly, androgen deficient men requiring testosterone implantation with the standard dose (four 200 mg pellets) were randomized into one of three groups (ratio 1 : 1 : 2): a four‐track abdomen site (standard), a two‐track abdomen site or a two‐track hip site. The pharmacological substudy was to evaluate the impact of site and track geometry on testosterone implant pharmacology by monthly hormone assays following implantation.PATIENTS Two hunded and forty‐six implantation procedures involving 96 androgen deficient men.MEASUREMENTS The primary end‐point, extrusion rate per procedure, and secondary end‐points (bruising or infection post procedure) were evaluated prospectively by self‐report from the participants, and verified when they returned next for implantation. The pharmacology substudy involved monthly blood sampling for hormone (total and free testosterone, LH, FSH) measurements.RESULTS The extrusion rate was significantly higher [odds ratio (OR) = 2·6, 95% confidence interval (CI) 1·1–7·1] for the hip site (15/125, 12%) compared with the abdominal site (6/121, 5%). Track geometry made no significant difference (OR = 1·05, 95% CI 0·2–5·4) to the extrusion rate. No secondary end‐points (bruising, infection) were significantly different according to either site or track geometry. One operator who performed the implant procedures had significantly less primary and secondary adverse events than the other operators (P = 0·006). Neither implantation site, nor track geometry influenced pharmacokinetics [peak plasma total and free testosterone concentrations and net hormone release (area‐under‐curve, AUC)] or pharmacodynamics [nadir plasma LH and FSH and net suppression (AUC) in men with hypergonadotrophic hypogonadism].CONCLUSIONS We conclude that the hip site has a higher extrusion rate than the standard abdominal wall site but that track geometry does not increase the risk of extrusion. Neither implantation site, nor track geometry influenced either other adverse effects or the pharmacokinetics or pharmacodynamics of testosterone pellet implants.
Chronic hypocalcaemia due to selective skeletal resistance to parathyroid hormone
Authors: Tucci Joseph R. 
Published: March 2003

A 71‐year‐old man was referred for evaluation of asymptomatic hypocalcaemia dating back at least 20 years. There were no somatic abnormalities and Chvostek and Trousseau signs were negative. Serum total calcium varied from 1·88 to 2·03 mmol/l, albumin 37–44 g/l, phosphate 0·54–1·12 mmol/l and ionized calcium 1–1·13 mmol/l. Serum intact PTH levels were 69 and 55 ng/l (10–65), 25‐OHD was 40 nmol/l (2·25–107·5) and 1,25‐(OH)2D was 54·6 nmol/l (39–156). Serum and urine magnesium and creatinine clearance were normal. Twenty‐four‐hour urine calcium was 2.15 mmol and calcium/creatinine ratio 0·07. TM phosphate (maximal rate of tubular reabsorption of phosphate in mmol/l glomerular filtrate (GF)) was 0·84 mmol/l GF (0·80–1·34). Bone formation and resorption markers were normal. Bone mineral densities measured by dual‐energy X‐ray absorptiometry (DEXA) were within normal limits at the hip, forearm and lumbar spine. Infusion of 200 units of synthetic 1–34 PTH was associated with a rise in urinary cyclic AMP from 43 mmol/l GF to 344 mmol/l GF and TM phosphate fell from 0·93 to 0·76 mmol/l GF; 1–34 PTH infusions of 300 units twice daily for 5 days were associated with an increase in serum 1,25‐(OH)2D from 80·6 to 114·4 pmol/l but no increase in serum calcium. This is a most unusual case of chronic hypocalcaemia similar to that reported by Frame et al. resulting from isolated skeletal resistance to PTH that is not related to renal insufficiency, osteomalacia or a magnesium‐deficient state. These two cases appear to represent a new variant of pseudohypoparathyroidism ?type III.
Effect of digoxin on the somatotroph responsiveness to growth hormone‐releasing hormone (GHRH) alone or combined with arginine in normal young volunteers
Authors: Broglio Fabio , Benso Andrea , Gottero Cristina , Di Vito Lidia , Granata Riccarda , Arvat Emanuela , Bobbio Marco , Trevi Giampaolo , Ghigo Ezio 
Published: March 2003

BACKGROUND The activity of the GH/IGF‐I axis, known to play a major role in myocardial structure and function, has been reported to be altered in patients with chronic heart failure.AIM AND DESIGN OF THE STUDY In order to evaluate the possibility that clinically used cardioactive drugs may exert neuroendocrine influences on somatotroph secretion, we studied the effects of pretreatment with enalapril (20 mg/day orally for 3 days), furosemide (20 mg i.v. as a bolus at − 5 minutes) or digoxin (0·25 mg orally 4×/day for 3 days) on the GH response to growth hormone‐releasing hormone (GHRH) (1·0 µg/kg i.v. as a bolus at 0 minutes) in 12 healthy male adults (age [mean ± SEM] 30·2 ± 1·4 years; BMI 22·7 ± 0·7 kg/m2). In a subgroup of 8 subjects the same study was performed testing the GH response to GHRH + arginine (ARG; 0·5 g/kg i.v. from 0 to + 30 minutes).RESULTS The GH response to GHRH (1304·1 ± 248·5 µg/l/h) was not modified by enalapril (1368·7 ± 171·2 µg/l/h) or by furosemide (1269·3 ± 185·2 µg/l/h) but was significantly blunted by digoxin (613·6 ± 73·2 µg/l/h, P < 0·05). On the other hand digoxin, enalapril and furosemide did not modify the GH response to GHRH + ARG.CONCLUSIONS Digoxin, but not enalapril or furosemide, inhibits the GH response to GHRH in normal subjects. The blunting effect of digoxin on the GHRH‐induced GH response is counteracted by arginine. These findings show that digoxin possesses an inhibitory effect on somatotroph secretion that may be mediated at the hypothalamic level.
Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency
Authors: Link Katarina , Bülow Birgitta , Westman Kerstin , Salmonsson Eva Cecilia , Eskilsson Jan , Erfurth Eva Marie 
Published: March 2003

OBJECTIVE In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV‐mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs.DESIGN AND PATIENTS Eleven patients with childhood onset GHD were investigated before and after 10 months of GH treatment at a dose of 1·5 IU/day (range 1–2), corresponding to 0·02 IU/kg/day or 7 μg/kg/day. The GH dose resulted in a serum IGF‐I level in the normal range in all but one patient.MEASUREMENTS Doppler echocardiography of the heart and ultrasound examination of the kidneys was performed. Glomerular filtration rate (GFR) was estimated with iohexol clearance and urinary proteinuria was measured with 24‐h urinary samples collected for analyses of albumin, alpha‐1‐microglobulin, IgG and albumin/creatinine clearance ratio. Body composition was measured by bioelectric impedance analysis.RESULTS L V‐mass index increased significantly after GH treatment (P = 0·04), and there was a clear trend for a positive correlation between the increase in serum IGF‐I and the increase in LV‐mass index, although it did not reach significance (r = 0·57, P = 0·07). GH treatment did not increase cardiac fractional shortening. Kidney length increased significantly (P = 0·02) with an average increase of 1 cm (range − 0·5–1·5 cm). No significant changes in median GFR or serum creatinine were recorded. Three patients with subnormal GFR before GH treatment normalized after 10 months of treatment. Urine analysis showed no abnormalities before or after GH treatment. A significant decrease in percentage fat mass was recorded (P = 0·03).CONCLUSION A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV‐mass index and kidney length. Re‐establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.
Somatostatin receptor 2 expression in the human endometrium through the menstrual cycle
Authors: Green V. L. , Richmond I. , Maguiness S. , Robinson J. , Helboe L. , Adams I. P. , Drummond N. S. , Atkin S. L. 
Published: March 2003

Summaryobjective Somatostatin mediates its many inhibitory functions through five G‐protein‐coupled receptors (sstr1−5); however, it is not known whether somatostatin or its receptors are present in the endometrium.design We have used immunohistochemistry on formalin‐fixed paraffin‐embedded sections of normal human endometrium from the menstrual (n = 6), proliferative (n = 15) and secretory (n = 10) stages of the endometrial cycle to determine the pattern of expression of somatostatin receptor (sstr) subtype 2. In addition, we have used quantitative polymerase chain reaction (PCR) to determine the level of expression of the sstr2 mRNA in 17 samples of normal human endometrium.patients Endometrial tissue had been removed from patients undergoing dilation and curettage (D&C) for menorrhagia and had been determined to be normal histologically.measurements Immunostaining in the epithelium, endothelium and the stroma of the endometrial sections was characterized and was scored positive or negative. The PCR results were analysed using the software provided to standardize the expression of sstr2 against that of constitutively expressed β‐glucoronidase in the same sample. A final percentage value of the level of sstr2 expression was then determined.results sstr2 was expressed variably throughout all the stages of the menstrual cycle in the epithelium, the endothelium and the stroma. In particular, the position of sstr2 expression varied in the epithelial cells surrounding the endometrial glands from being basal or diffuse in the proliferative and secretory phase to being lumenal in the menstrual stage. Quantitative PCR showed that 15 of 17 samples expressed sstr2 mRNA and the level of expression between individual samples varied dramatically.conclusions These data show that sstr2 is present in the endometrium and its location seems to vary through the menstrual cycle.
Prospective 10‐year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy
Authors: Wu Fiona , Ames Ruth , Clearwater Judy , Evans Margaret C. , Gamble Greg , Reid Ian R. 
Published: March 2003

Summaryobjective To prospectively assess bone density and the factors determining the rate of bone loss over a 10‐year period of postmenopausal life.design Prospective, observational study.methods One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47–71 years) completed the study (mean duration of follow‐up 10·2 years, range 9·4–10·6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual‐energy X‐ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed.results Twenty‐four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow‐up. The mean duration of therapy was 6·6 years (range 2·8–10·4 years). The use of HRT was associated with significant gains in bone density (total body + 3·0%, trochanter + 4·2%, Ward's triangle + 4·4%, spine + 10·5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non‐HRT users 0·42 (confidence interval 0·18–0·83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow‐up bone densities in the non‐HRT users were highly correlated (0·82 ≤ r ≤ 0·91, P ≤ 0·0001) and baseline bone density accounted for the majority of the variance in the 10‐year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow‐up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health).conclusions Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long‐term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.