bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults
Authors: Johannsson Gudmundur , Rosén Thord , Bengtsson Bengt‐Åke 
Published: November 2003

OBJECTIVEUntil now, GH treatment in GH‐deficient adults has employed dose schedules of GH based on body weight or body surface area and has ignored individual responsiveness to GH. This trial has studied the effects of an individualized GH dose adjusted to match a combination of clinical response, normalization of serum IGF‐I concentration and body composition.DESIGN AND PATIENTSTwo closely‐matched groups, each comprising 30 GH‐deficient adults, 38 men and 22 women aged 48 years, were treated with GH for 12 months. The high dose (HD) group received a target dose of 12 μg/kg per day and the individualized dose (ID) group received an initial daily GH dose of 0.17 or 0.33 mg per day (0.5 and 1 IU, respectively), independent of body weight, with dose adjustments thereafter.MEASUREMENTSSerum concentrations of IGF‐I, lipoprotein(a), insulin, calcium, intact PTH, osteocalcin and blood glucose were measured. Body composition was determined according to a 4‐compartment model using total body potassium and tritiated water as input variables. Total body nitrogen was measured by in vivo neutron activation and total body bone mineral content by dual energy X‐ray absorptiometry.RESULTSAt 12 months, the daily dose of GH was 0.55 ± 0.03 mg and 0.45 ± 0.03 mg in the HD and ID groups, respectively (P < 0.05). In the HD group, the mean serum IGF‐I increased to levels well above the predicted level, while in the ID group the mean serum IGF‐I normalized. Side‐effects were experienced by 70% of the subjects in the HD group and by 30% in the ID group (P < 0.001). A similar response to GH in terms of body composition, glucose homeostasis, lipoprotein(a) and blood pressure was obtained in both treatment groups. However, the treatment response in terms of serum calcium, intact PTH and osteocalcin was more marked in the HD group.CONCLUSIONSSimilar efficacy, with a lower dose of GH and fewer side‐effects, was obtained by considering individual responsiveness to GH as compared to higher doses of GH adjusted to match body weight.
The role of radioactive iodine in the treatment of advanced differentiated thyroid carcinoma
Authors: Pelikan D. M. V. , Lion H. L. , Hermans J. , Goslings B. M. 
Published: November 2003

OBJECTIVE 131I therapy may be beneficial for patients with advanced differentiated thyroid cancer (DTC) but there have been relatively few studies of the prognostic factors which influence the outcome. We have evaluated differences in outcome in relation to histology, localization of tumour, differentiation grade, age and sex after 131I as the only secondary treatment for advanced stages of DTC.DESIGNRetrospective study of a selected patient group treated according to a fixed protocol.PATIENTSWe studied the outcome in 86 patients with stage pN3, pT4 or pM1 out of total of 432 patients treated for DTC from 1970 until 1991.RESULTSThe overall cure rate of 131I therapy after a mean follow‐up of 12.1 years was 50% (papillary 65% vs follicular 23%). The overall 5‐year progression free survival (PFSR) was 66%. Three out of 11 patients with bone metastases from follicular cancer were cured after a mean dose of 13.2 GBq, significantly less than the average dose of 28.4 GBq given to all patients with bone metastases. In the univariate analysis of 5‐year PFSR histology (papillary 79% vs follicular 43%), differentiation grade (well differentiated 81% and moderately differentiated 31%), tumour stage (pN3100%, pT4 77% and M1 48%), and age (≤ 60 years 85% vs > 60 years 46%) were significant prognostic factors. A multivariate analysis showed differentiation grade, histology and age to be significant prognostic variables for outcome (moderately vs well differentiated: RR = 3.16, follicular vs.papillary: RR = 2.56 and age > 60 vs age ≤ 60: RR = 2.43).CONCLUSIONS 131I can be an effective treatment in patients with advanced differentiated thyroid cancer at all sites and can cure, on average, 50% of all patients with advanced differentiated thyroid cancer.
Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types
Authors: Corbetta Sabrina , Pizzocaro Alessandro , Peracchi Maddalena , Beck‐Peccoz Paolo , Faglia Giovanni , Spada Anna 
Published: November 2003

OBJECTIVEWe have investigated the prevalence of MEN 1 in patients with recognized pituitary adenomas. Since hyperparathyroidism is present in nearly 95–100% of patients with MEN 1 and frequently is the first condition to be identified, the study was limited to the identification of patients with hyperparathyroidism while the screening for gastroenteropancreatic (GEP) lesions was carried out in patients with both pituitary and parathyroid lesions.PATIENTS AND MEASUREMENTSSerum total and ionized calcium, phosphate and intact PTH 1‐84 (EASIA) were measured in 166 patients (68 with non‐functioning pituitary adenoma, 42 with prolactinoma, 35 with GH‐secreting adenoma, 17‐with ACTH‐screening adenoma, 1 with TSH‐secreting adenoma, 1 with FSH‐secreting adenoma and 2 with an only α‐subunit secreting adenoma) referred to our clinic from 1990 to 1996. Plasma gastrin, somatostatin, pancreatic polypeptide and vasoactive intestinal peptide were measured by RIA in patients with hyperparathyroidism.RESULTSEight of 166 patients (4.8%) were found to have primary hyperparathyroidism and among these 2 also had a gastrinoma while there was no evidence of other GEP tumours. Considering the tumour type, 6 had prolactinoma (14.3%), 1 GH‐secreting adenoma (2.8%) and 1 non‐functioning adenoma (1.5%). In most patients the diagnosis of pituitary tumour was made several years before that of hyperparathyroidism (from 1 to 15 years) although 6 patients had previously suffered from urolithiasis and one had undergone gastric resections for recurrent peptic ulcers. One patient was identified as a MEN 1 gene carrier and 2 had relatives with signs and symptoms referable to parathyroid or GEP lesions.CONCLUSIONSThe study shows a prevalence of 4.8% of primary hyperparathyroidism in unselected patients with known pituitary tumours similar to that reported in a previous study. By contrast, the prevalence of MEN 1 in patients with prolactinoma was definitely high (14.3%). In most patients the diagnosis of pituitary tumours was made several years before that of hyperparathyroidism. Although the patients were believed to harbour a sporadic pituitary tumour, most of them had had signs and/or symptoms referable to one or both of the other organs involved in MEN 1, often concomitantly with those of pituitary tumours. These data indicate that the diagnosis of MEN 1 syndrome is missed in a substantial proportion of patients with prolactinomas and therefore the screening of these patients for the syndrome is strongly recommended.
Lower cortisol levels after oral glucose in subjects with insulin resistance and abdominal obesity
Authors: Fernández‐Real José‐Manuel , Ricart Wifredo , Casamitjana Roser 
Published: November 2003

BACKGROUNDIt has been shown previously that morning cortisol levels decline after oral glucose, but no report has been published regarding the changes in serum cortisol in relation to insulin sensitivity or degree of obesity.SUBJECTS AND DESIGNWe studied the effects of oral glucose during a standard oral glucose tolerance test on cortisol levels in 7 obese subjects (body mass index (BMI) 29.7 ± 3.3 kg/m2) and in 8 control subjects (BMI 24.9 ± 3.2 kg/m2). Cortisol concentrations were normalized to time 0 because of wide between subject variation. On another day, a frequently sampled intravenous glucose tolerance test with minimal model analysis was performed, obtaining the insulin sensitivity index (SI). Anthropometric measurements included different skinfolds and bioelectric impedance.RESULTSThe waist‐to‐hip ratio (WHR) was similar between the 2 groups, but abdominal skinfold was significantly higher in the obese group (OG) (158.8 ± 42.9 vs. 113.6 ± 27.7,P = 0.03). Fat mass, percentage of fat mass, triceps and subscapular skinfolds, systolic and diastolic blood pressure, VLDL‐cholesterol, total triglycerides and VLDL‐triglycerides were slightly higher in the obese group (OG). Area under the curve for glucose (AUCg) after OGTT was also significantly higher in OG (9.9 ± 2.4 vs. 7.1 ± 0.5 mmol/l, P = 0.02) in contrast to area under the curve for insulin (102 ± 60 vs. 73.8 ± 26.7 mU/l, P = NS), or glucose effectiveness (0.015 ± 0.004 vs. 0.015 ± 0.009 min−1, P = NS). Subjects with the highest WHR of both groups exhibited a greater cortisol suppression (56 ± 0.09 vs. 41 ± 0.17, P = 0.05). Normalized serum cortisol after OGTT was significantly lower from minute 60 to 120 in the OG (P = 0.001, 0.003 and 0.01 at 60, 90 and 120 minutes, respectively). The maximal cortisol suppression was 59.2% in the OG in comparison with 43% in the control group (P = 0.027). This maximal cortisol suppression correlated weakly with the maximal insulin response after oral glucose (r = 0.49, P = 0.07). In a multiple linear regression analysis, with maximal cortisol suppression as dependent variable, both BMI (P = 0.03) and SI (0.02) contributed to the variance of maximal cortisol suppression (R2 = 0.40).CONCLUSIONWe show that differences in cortisol decline are at least partially attributed to differences in insulin sensitivity and to differences in abdominal fat. This abdominal‐related decrease of cortisol might support the concept that the increased visceral adipose tissue mass with a high density of glucocorticoid receptors enhances the metabolism of cortisol. Perhaps the subjects with higher abdominal fat or insulin resistance are prone to lower cortisol levels after carbohydrate‐rich intakes in the morning. These lower cortisol levels, behaving as a positive feed‐back signal, might generate higher ACTH and cortisol responses after protein‐rich meals at mid‐day.
Regionalization of occult pancreatic insulinomas with the arterial stimulation venous sampling (ASVS) technique
Authors: Tsagarakis S. , Kaskarelis J. , Malagari C. , Platis O. , Trivizas P. , Vrachliotis G. , Thalassinos N. 
Published: November 2003

Non‐invasive modalities (ultrasound, computerized tomography, MRI and somatostatin receptor scintigraphy) often fail to localize insulinomas smaller than 1.5 cm in diameter. Recently, regionalization of such occult insulinomas was facilitated by the arterial stimulation and venous sampling (ASVS) technique, using calcium as the insulin secretagogue. However, so far experience with this technique has been limited to a few tertiary referrals centres worldwide. In these case studies we report our experience in three consecutive patients with occult insulinomas.Three consecutive patients (all men 34, 51 and 56 years of age) with insulin‐mediated hypoglycaemia were studied. Diagnosis of insulin hypersection was established by the finding of a high amended insulin : blood sugar ratio during fasting. Localization of a pancreatic mass lesion was unsuccessful by ultrasound, CT and/or MRI in all patients. Two patients had negative octreotide scans. In all patients after the infusion of calcium sequentially into the gastroduodenal, splenic and the superior mesenteric arteries, insulin levels rose significantly in right hepatic vein samples giving rise to diagnostic gradients from the splenic artery (in 2 patients) and gastroduodenal artery (in 1 patient), regionalizing insulinomas in the tail and head or neck of the pancreas respectively. The simultaneously obtained angiogram was positive in only 1 patient, in whom it corresponded to the insulin gradient. Regionalization of these occult tumours was subsequently confirmed at laparoscopy in the 2 patients operated.It is concluded, that the arterial stimulation venous sampling technique is an effective method in regionalizing occult insulinomas and should complement invasive angiography whenever the latter procedure is performed.
Frequency of a polymorphism in the regulatory region of the 17α‐hydroxylase‐17,20‐lyase (CYP17) gene in hyperandrogenic states
Authors: Techatraisak K. , Conway G. S. , Rumsby G. 
Published: November 2003

OBJECTIVE Dysregulation of 17α‐hydroxylase (CYP17) has been proposed as a cause of hyperandrogenism. We have determined the prevalence of a polymorphic allele in the CYP17 gene in sporadic patients with polycystic ovaries (PCOS) compared to a reference population, and to a group of hyperandrogenic individuals, to assess its significance to androgen production.PATIENTS AND DESIGN DNA was isolated from EDTA blood samples from 69 patients with PCOS, 63 patients with congenital adrenal hyperplasia secondary to 21‐hydroxylase deficiency and 124 consecutive patients attending for a full blood examination. The thymine (T) to cytosine (C) polymorphism at −34 base pairs (bp), denoted alleles A1 and A2 respectively, was detected by amplification of DNA followed by restriction enzyme digestion.MEASUREMENTS Testosterone and LH. The frequency of alleles A1 and A2 in each of the subject groups was determined.RESULTS The prevalences of the A1 and A2 alleles were 75 and 25% respectively in the PCOS group which was not significantly different from that in either the hyperandrogenic or the reference group. Neither allele segregated with hyperandrogenism.CONCLUSION The polymorphism plays no apparent role in the dysregulation of CYP17.
Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption
Authors: Francis R. M. , Harrington F. , Turner E. , Papiha S. S. , Datta H. K. 
Published: November 2003

OBJECTIVE Previous studies have suggested that polymorphism of the alleles of the vitamin D receptor (VDR) gene may account for the major part of the heritable component of bone density in women, possibly mediated in part by impaired calcium absorption from the bowel. In view of the increasing importance of osteoporosis in men, we have now investigated the association between common allelic variations in the vitamin D receptor gene, calcium absorption and bone density in men. SUBJECTS  Forty‐eight men (median age 64, range 27–77) with a wide range of bone density measurements, comprising 20 men with vertebral crush fractures and 28 male control subjects. MEASUREMENTS Analysis of the VDR gene polymorphism and measurement of fractional radiocalcium absorption and bone mineral density was performed in all subjects. RESULTS The distribution of the three genotypes (TT, tt, Tt) was comparable to that reported previously. There was no significant difference in femoral neck bone density Z‐scores between the three genotypes (mean±SD TT −0.31±1.19, tt −0.08±001.28 and Tt −0.37±1.17). There were also no significant differences in mean femoral neck bone density T‐scores or lumbar spine bone density Z or T‐scores between the three genotypes. Fractional radiocalcium absorption was 0.59±0.27 for TT, 0.69±0.30 for tt and 0.60±0.30 for Tt, showing no significant difference between the genotypes. CONCLUSIONS This study shows no association between vitamin D receptor gene polymorphism and bone density or fractional calcium absorption in a group of men with a range of bone density values. We conclude that the vitamin D receptor gene alleles probably account at most for only a small part of the genetic component of bone density in men.
Intracellular calcium ion responses to somatostatin in cells from human somatotroph adenomas
Authors: Chen Zhen‐Ping , Xu Su , Lightman Stafford L. , Hall Len , Levy Andrew 
Published: November 2003

OBJECTIVE Various GH secretory responses to long‐acting somatostatin (SRIH) analogues have been observed during the treatment of acromegalic patients. The effects of SRIH on intracellular Ca2+ homeostasis in human somatotroph adenoma cells has not been examined in detail, and the underlying mechanisms therefore remain to be determined. Using isolated cells from human somatotroph adenomas, we have investigated the SRIH‐induced intracellular Ca2+ responses at a single‐cell level with computerized real time intracellular calcium ion (Ca2+i) imaging. PATIENTS Adenoma specimens were obtained from 4 male and 11 female acromegalic patients (mean age 56, range 26–72 years) undergoing transsphenoidal hypophysectomy. METHODS The identity of the biopsy material obtained was confirmed by immunocytochemistry for hGH and in situ hybridization histochemistry using a 35S end‐labelled hGH oligodeoxynucleotide probe and probes complementary to proopiomelanocortin and prolactin. Genomic DNA coding for somatostatin receptor (SSTR2) from each adenoma was PCR amplified and sequenced. Cells cultured from these adenoma were subject to computerized real time intracellular Ca2+i imaging at a single cell level. RESULTS In cells from 11 of the 15 adenomas, SRIH produced a reversible, dose‐independent reduction in [Ca2+]i from the mean of 167±11 to 43±3 nM within 51±1.8s, and blocked the growth hormone releasing hormone (GRH)‐induced increase in [Ca2+]i as expected. In the same adenomas, withdrawal of SRIH after a 30 second exposure produced a small but significant increase in resting [Ca2+]i. Pretreatment with pertussis toxin abolished the SRIH‐induced inhibition of [Ca2+]i and prevented the SRIH‐induced inhibition of the effect of GRH on [Ca2+]i. One of the remaining 4 adenomas was completely unresponsive to SRIH despite responding vigorously to other ligands and immunostaining strongly for GH. Surprisingly, cells from 3 adenomas showed a paradoxical increase in [Ca2+]i in response to SRIH in some or, in one case, all of the cells examined. In all adenomas the sequence of SSTR2 corresponded to wild‐type. CONCLUSIONS In the majority of cells derived from human somatotrophic adenomas, SRIH caused a reduction in baseline [Ca2+]i and inhibition of GRH‐induced [Ca2+]i increase, as observed in somatotrophs of other species. In addition, SRIH was found either to induce a paradoxical increase in [Ca2+]i or to have no effect on [Ca2+]i in a small proportion of somatotroph adenomas examined. This finding corroborates the clinical observation that the response to SRIH analogues varies markedly between somatotroph adenoma patients. There was no evidence of SSTR2 mutations in any of the adenomas examined.
Changes in dimeric inhibin A and B during normal early puberty in boys and girls
Authors: Crofton P. M. , Illingworth P. J. , Groome N. P. , Stirling H. F. , Swanston I. , Gow S. , Wu F. C. W. , McNeilly A. , Kelnar C. J. H. 
Published: November 2003

OBJECTIVE Although recently developed specific and sensitive assays of bioactive dimeric inhibin A and B have given new insights into the pituitary‐gonadal axis in adult men and during the adult female menstrual cycle, there have been no reports on circulating inhibin A and B during normal human puberty. The aim of this study was to assess the relationship of dimeric inhibin A and B to pubertal stage, FSH and testosterone or oestradiol in late prepuberty and in early puberty. STUDY DESIGN AND SUBJECTS Serial samples were collected during a prospective longitudinal trial of GH treatment in short normal children. Seven boys were studied from late prepuberty to genital stage 3, and six pre‐menarche girls from late prepuberty to breast stage 4. MEASUREMENTS Dimeric inhibin A (girls only) and inhibin B (boys and girls) were measured by highly specific and sensitive two‐site ELISAs, FSH by IRMA, testosterone and oestradiol by RIA. RESULTS In boys, inhibin B increased progressively from pubertal stages 1 to 3 (ANOVA P<0.0001) and correlated strongly with mean testicular volume (r=0.72, P=0.0005). Prepubertal boys showed a positive correlation between inhibin B and FSH (r=0.65, P=0.056), whereas pubertal boys gave a strong negative correlation (r=0.75, P=0.012). In both prepubertal and pubertal boys positive correlations were observed between inhibin B (y) and testosterone (x) (r=0.81, P=0.008 and r=0.62, P=0.054 respectively), but the slope of the regression line between the two was much steeper before than after the onset of clinical puberty. In girls, both inhibin A and B increased through pubertal stages 1–4 (ANOVA P=0.01 and P=0.047 respectively). Both showed strong positive correlations with oestradiol (r=0.80 and 0.79, P=0.001) and with FSH (r=0.83, P=0.0004 and r=0.80, P=0.001). Inhibin A and B were also strongly correlated with each other (r=0.92, P=0.0001). CONCLUSIONS In boys, testicular production of inhibin B increases as puberty progresses. Our results show for the first time that the initiation of puberty is accompanied by a dramatic switch from a positive to a negative relation between inhibin B and FSH as inhibin B begins to exert the expected negative feedback on FSH. The results in girls suggest that, prior to menarche, the ovarian follicles produce inhibin A and B in strict proportion, and in progressively greater amounts as puberty proceeds. Measurement of dimeric inhibin A and B may provide a sensitive new tool for determining gonadal maturity in late prepuberty and early puberty.
Cervex brush versus vaginal–cervical–endocervical (VCE) triple smear techniques in cervical sampling
Authors: JÄRVI K 
Published: November 2003

Cervex brush versus vaginal–cervical–endocervical (VCE) triple smear techniques in cervical samplingCervex brush sampling was compared with the conventional triple vaginal–cervical–endocervical (VCE) smear technique. Nine hundred and fifty‐nine Cervex brush smears and 1064 VCE smears were studied. All smears with both methods were technically satisfactory for evaluation. Endocervical cells were found in 90.7% and metaplastic cells in 73.3% of Cervex brush samples and in 92.5% and 64.1% of VCE samples, respectively. There were significantly more metaplastic cells in smears from premenopausal women. Low grade squamous intraepithelial lesion (SIL) was found in three Cervex brush samples and in two VCE samples. High‐grade SIL was found only in one Cervex brush sample. Benign cellular changes were found in 142 Cervex brush samples and in 144 VCE samples. Sampling with the Cervex brush is efficient, simple and fast and gives high quality cervical smears for cytological evaluation.
Image analysis of low magnification images of fine needle aspirates of the breast produces useful discrimination between benign and malignant cases
Authors: CROSS S. S. , BURY J. P. , STEPHENSON T. J. , HARRISON R. F. 
Published: November 2003

Image analysis of low magnification images of fine needle aspirates of the breast produces useful discrimination between benign and malignant casesFine needle aspirates of the breast (FNAB) (n=362; 204 malignant, 158 benign), prepared by cytocentrifuge methods and stained by the Papanicolaou technique, were analysed using a semi‐automated image analysis system at a low magnification which precluded resolution of nuclear detail. The measured parameters were integrated optical density, fractal textural dimension, number of cellular objects (single cells and contiguous groups of cells), distance between cellular objects (mean, s.d., skewness and kurtosis), area of cellular objects (mean, s.d., skewness, kurtosis) and the nearest neighbour statistic. The cases were divided into a 200‐case training set and a 162‐case test set. Analysis was performed by logistic regression and the multi‐layer Perceptron type of artificial neural network. Logistic regression and the neural network produced similar performances with a sensitivity of 82–83%, specificity 85% and a positive predictive value for a malignant result of 85%. A non‐parametric analysis of all the predictor variables showed that all except the mean area of cellular objects and the s.d. of this measurement were significant discriminants (P<0.05), but most were highly interrelated and this was reflected in the selection of only three predictor variables by forward and backward conditional logistic regression. This study shows that much diagnostic information is present in low power views of FNAB, and that image analysis could form the basis of a semi‐automated decision‐support aid.