bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polysomnographic findings in five adult patients with pituitary insufficiency before and after cessation of human growth hormone replacement therapy
Authors: Nolte Wilhelm , Rädisch Carsten , Rodenbeck Andrea , Wiltfang Jens , Hüfner Michael 
Published: March 2003

Summaryobjective We observed the new onset of severe obstructive sleep apnoea syndrome (OSAS) in an adult male patient during human growth hormone (hGH) replacement therapy. This prompted us to evaluate the potential influence of hGH substitution therapy on sleep in middle‐aged men.design A longitudinal study.subjects Five male patients (aged 44–56 years, median age 54 years) with postoperative pituitary insufficiency given hGH replacement therapy for 1–2 years (median dose 2·0 U/day; median IGF‐I serum concentration 351 µg/l) and 6 months after cessation of hGH treatment (median IGF‐I level 77 µg/l – 1 µg/l = 0·131 nmol/l).measurements Polysomnographic studies were performed, and the following parameters were determined: time in bed (TIB), sleep period time (SPT), total sleep time (TST), sleep efficiency (SE = TST/TIB), sleep stage 1 onset latency (SL), different sleep stages [W (wake), S1, S2, SWS (slow wave sleep = S3 + S4) and REM; % of SPT], stage shifts per hour of SPT (SS/h), stage shifts to W/h of SPT [A/h (awakening)], index of apnoea and hypopnoea events per hour of TST (AH/h), arousals from apnoea and hypopnoea per hour of TST (Ar/h), index of obstructive (OAH/h), central (CAH/h) and mixed (MAH/h) events of apnoea and hypopnoea per hour of TST and minimal desaturation (MD).results Median baseline results were: TIB, 479 min; SPT, 465 min; TST, 405 min; SE, 77%; SL, 8·5 min; W, 18·9%; S1, 8·2%; S2, 52·7%; REM, 13·5%; SS/h, 17·7; A/h, 2·8; AH/h, 11·9; Ar/h, 4·4; MD, 80%. These parameters did not change significantly after cessation of hGH treatment. In contrast, median SWS decreased significantly from 33 min (7·1%) to 7·5 min (1·8%; P = 0·03). Median OAH/h decreased significantly from 4·4 to 0·1 (P = 0·03) whereas CAH/h increased from 6·3 to 14·6 (P = 0·03) after cessation of hGH. Correspondingly, one patient with OSAS improved markedly whereas another patient developed new and asymptomatic central SAS after cessation of hGH.conclusion This study showed that hGH replacement therapy influenced sleep reaction in a complex way in middle‐aged men; cessation of treatment was associated with a significant decrease in slow wave sleep and a shift from obstructive to central apnoea and hypopnoea.
Effects of glucose, free fatty acids or arginine load on the GH‐releasing activity of ghrelin in humans
Authors: Broglio Fabio , Benso Andrea , Gottero Cristina , Prodam Flavia , Grottoli Silvia , Tassone Francesco , Maccario Mauro , Casanueva Felipe F. , Dieguez Carlos , Deghenghi Romano , Ghigo Ezio , Arvat Emanuela 
Published: March 2003

Summaryobjective Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n‐octanoyl ester in serine‐3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS‐R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone‐releasing hormone (GHRH) and non‐natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non‐natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH‐releasing effect of ghrelin in humans have not been fully clarified.subjects To this aim we enrolled six normal young volunteers [age (mean ± SEM) 28·9 ± 3·1 year; body mass index 22·3 ± 1·0 kg/m2).design and measurements In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at −45 min) or free fatty acids (FFA) load [lipid–heparin emulsion, Li–He, Intralipid 10% 250 ml + heparin 2500 U i.v. from −30 to +120 min] as well as of arginine (ARG, 0·5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1·0 µg/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li–He and ARG on the GH response to GHRH‐29 (1·0 µg/kg i.v. at 0 min).results The GH response to ghrelin (auc 5452·4 ± 991·3 µg/l/h) was higher (P < 0·05) than that after GHRH (1519·4 ± 93·3 µg/l/h). The GH response to GHRH was inhibited by OGTT (450·7 ± 81·1 µg/l/h, P < 0·05) and almost abolished by Li–He (230·0 ± 63·6 µg/l/h, P < 0·05) while was markedly potentiated by ARG (2520·4 ± 425·8 µg/l/h, P < 0·05). The GH response to GHRH + ARG, however, was lower (P < 0·05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153·1 ± 781·9 µg/l/h, P < 0·05) as well as by Li–He (3158·8 ± 426·7 µg/l/h, P < 0·05) but these responses remained higher (P < 0·05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324·3 ± 1275·5 µg/l/h). For GH 1 µg/l = 2 mU/l.conclusions In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non‐natural GHS acts, at least partially, by antagonizing SS activity.
Localization of gastrinomas by selective intra‐arterial calcium injection
Authors: Turner J. J. O. , Wren A. M. , Jackson J. E. , Thakker R.V. , Meeran K. 
Published: March 2003

SummaryBackground Preoperative localisation is important for successful surgical treatment of gastrinomas. However, a satisfactory method that achieves this has not been defined, and at present somatostatin receptor scintigraphy and selective intra‐arterial stimulation testing with secretin have the greatest sensitivities. As secretin is now difficult to obtain, we decided to explore the use of calcium gluconate as a secretagogue. High extracellular calcium concentrations cause degranulation of neuroendocrine cells and subsequent release of hormone.Methods Two patients with biochemically proven gastrinomas were investigated pre‐operatively. Under angiographic control calcium gluconate was injected into the arteries supplying the pancreas and duodenum, gastrin levels were then determined in hepatic vein samples obtained before and 30, 60, 90, 120 and 180 seconds after each injection. One of the patients had also previously undergone selective intra‐arterial stimulation testing with secretin.Results Calcium gluconate produced sharp peaks of gastrin which unequivocally localised the tumour to a specific vascular territory in each case. Furthermore, surgery confirmed the localisations of the gastrinomas. Calcium injection, unlike secretin, into vascular territories without gastrinomas caused no rise in gastrin, thereby demonstrating calcium's greater specificity.Conclusions Calcium gluconate is a highly sensitive and specific alternative secretagogue to secretin for localisation of pancreatic and duodenal gastrinomas. Furthermore calcium gluconate was found to demonstrate the territory of the tumour more accurately than secretin.
Gender‐related differences in erythrocyte glutathione peroxidase activity in healthy subjects
Authors: Massafra Cosimo , Gioia Dino , De Felice Claudio , Muscettola Michela , Longini Mariangela , Buonocore Giuseppe 
Published: March 2003

Summaryobjective The antioxidant property of oestrogens may partly explain the gender differences in atherosclerotic heart disease and a reduction in the incidence of coronary heart disease, as well as mortality from cardiovascular disease in women undergoing postmenopausal oestrogen therapy. In the present study, we tested the hypothesis that the antioxidant glutathione peroxidase (GSH‐Px) erythrocyte activity is gender related and is correlated with oestradiol serum levels.patients One hundred and fifty healthy women (90 premenopausal; 60 postmenopausal) and 150 age‐matched healthy men were recruited during routine health screening.design and measurements Serum was analysed for oestradiol (E2), progesterone and testosterone concentrations, and erythrocytes for GSH‐Px enzyme activity. Thirty of the 60 postmenopausal women were treated with transdermal therapy for 30 days with 8‐mg E2 patches (nominal daily dose 100 µg), while the remaining 30 acted as controls.results Erythrocyte GSH‐Px activity was significantly higher in premenopausal than in postmenopausal women (P = 0·0014), and higher in premenopausal women than in age‐matched men (P = 0·025). By contrast, no significant differences were observed between postmenopausal women and the age‐matched male population. In postmenopausal women, E2 replacement therapy induced a significant increase in erythrocyte GSH‐Px activity (P < 0·001). GSH‐Px was positively correlated with serum E2 levels in both premenopausal (r = 0·26, P = 0·011) and postmenopausal women treated with oestrogen replacement therapy (r = 0·42, P = 0·022). No significant correlations in the female population were found between GSH‐Px erythrocyte activity and the other sex steroid hormones examined (r2 ≤ 0·10, P ≥ 0·45). No statistically significant correlations were found between GSH‐Px and E2, progesterone and testosterone in the male population (r2 ≤ 0·15, P ≥ 0·30).conclusions Our findings support the hypothesis that oestrogens are responsible for the sex‐related differences in glutathione peroxidase activity. The hypothesis generated from the present study can be tested directly in experimental models involving specific bone marrow cells by analysis of specific glutathione peroxidase transcriptional changes.
Thyroid stimulating hormone (TSH) concentrations and menopausal status in women at the mid‐life: SWAN
Authors: Sowers MaryFran , Luborsky Judy , Perdue Craig , Araujo Katy L. B. , Goldman Marlene B. , Harlow Siobán D. 
Published: March 2003

Summaryobjective We evaluated menopausal symptoms, menstrual cycle bleeding characteristics and reproductive hormones for their associations with thyroid stimulating hormone (TSH) concentrations in women at the mid‐life from five ethnic groups.methods This report is from the baseline evaluation of the Study of Women's Health Across the Nation (SWAN), a community‐based multiethnic study of the natural history of the menopausal transition. Enrollees were 42–52 years old (pre‐ and early perimenopausal) African American, Caucasian, Chinese, Hispanic and Japanese women (n = 3242). Enrollees were interviewed about self‐reported diagnosed hypo‐ and hyperthyroidism or thyroid treatment, menopausal symptoms and menstrual cycle bleeding characteristics. Serum was assayed for TSH, oestradiol, testosterone, FSH and SHBG.results There were 6·2% of women with TSH > 5·0 mIU/ml and 3·2% with TSH < 0·5 IU/ml, cutpoints that have been used to encompass clinical and subclinical hypo‐ and hyperthyroidism, respectively. African American women had significantly lower mean TSH concentrations than Caucasian, Hispanic and Chinese women. Of the more than 15 menopause symptoms evaluated, only fearfulness was associated with having a TSH value > 5·0 mIU/ml (P < 0·008) or < 0·5 mIU/ml (P < 0·02). Women with TSH values outside the range of 0·5–5·0 mIU/ml were more likely to report shorter or longer menstrual periods (P = 0·004 for both) than women within that range. FSH, SHBG, dehydroepiandrosterone sulphate (DHEA‐S), testosterone, and oestradiol concentrations were not associated with TSH concentrations.conclusion In mid‐aged women, there was a 9·6% prevalence of TSH values outside the euthyroid range of 0·5–5·0 mIU/ml. Although TSH was associated with bleeding length and self‐reported fearfulness, it was not associated with indicators of the menopausal transition, including menopausal stage defined by bleeding regularity, menopausal symptoms or reproductive hormone concentrations.
The outcome in Australian children with hyperinsulinism of infancy: early extensive surgery in severe cases lowers risk of diabetes
Authors: Jack Michelle M. , Greer Ristan M. , Thomsett Michael J. , Walker Rosslyn M. , Bell John R. , Choong Catherine , Cowley David M. , Herington Adrian C. , Cotterill Andrew M. 
Published: March 2003

SummaryaimsHyperinsulinism of infancy (HI) is characterized by unregulated insulin secretion in the presence of hypoglycaemia, often resulting in brain damage. Pancreatic resection for control of hypoglycaemia is frequently resisted because of the risk of diabetes mellitus (DM). We investigated retrospectively 62 children with HI from nine Australian treatment centres born between 1972 and 1998, comparing endocrine and neurological outcome in 28 patients receiving medical therapy alone with 34 who required pancreatic resection to control their hypoglycaemia.methodsHistory, treatment and clinical course were ascertained from file audit and interview. Risk of DM (hazard ratio) attributable to age at surgery (< vs. ≥ 100 days at last pancreatectomy) and extent of resection (< vs. ≥ 95%) were calculated using Cox proportional hazards regression and categorical variables compared by the χ2‐test. Neurological outcome (normal, mild deficit or severe deficit) was derived from the most authoritative source.resultsSurgically treated patients had a greater birthweight, earlier presentation and higher plasma insulin levels. Of 18 infants < 100 days and 16 ≥ 100 days of age at surgery, four (all ≥ 100 days) became diabetic as an immediate consequence of surgery and five (two < 100 days and three ≥ 100 days) became diabetic 7–18 years later. Surgery ≥ 100 days and pancreatectomy ≥ 95% were associated with development of diabetes (HR = 12·61, CI 1·53–104·07 and HR = 7·03, CI 1·43–34·58, respectively). Neurodevelopmental outcome was no different between the surgical and medical groups with 44% overall with neurological deficits. Patients euglycaemic within 35 days of the first symptom of hypoglycaemia (Group A) had a better neurodevelopmental outcome than those still hypoglycaemic > 35 days from first presentation (Group B) (P = 0·007). Prolonged hypoglycaemia in Group B was due either to delayed diagnosis or to need for repeat surgery because of continued hypoglycaemia. Within Group A, medically treated patients (who presented later with apparently milder disease) had a higher incidence of neurodevelopmental deficit (n = 15, four mild, three severe deficit) compared with surgically treated patients (n = 18, two mild, none severe deficit) (P < 0·025).conclusionsPoor neurodevelopmental outcome remains a major problem in hyperinsulinism of infancy. Risk of diabetes mellitus with pancreatectomy varies according to age at surgery and extent of resection. Patients presenting early with severe disease have a better neurodevelopmental outcome and lower risk of diabetes if they are treated with early extensive surgery.
Diagnostic value of qualitative and quantitative variables in thyroid lesions
Authors: Rout P. , Shariff S. 
Published: March 2003

Diagnostic value of qualitative and quantitative variables in thyroid lesionsTwo hundred and thirty‐three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin‐laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.
Radial scar/complex sclerosing lesion—a problem in the diagnostic work‐up of screen‐detected breast lesions
Authors: Orell S. R. 
Published: March 2003

Radial scar/complex sclerosing lesion—a problem in the diagnostic work‐up of screen‐detected breast lesionsDuring the first 7.5 years of breast cancer screening in South Australia, 88 radial scar/complex sclerosing lesions were among the mammographically detected abnormalities. A false‐positive cytological diagnosis by fine needle biopsy was given in three of 69 such cases with satisfactory smears, a false‐positive rate of 4.3% in this particular group. A review of the smears suggested that the false‐positive diagnoses could have been avoided if a total or near total absence of a benign epithelial component had been included among the criteria for a malignant diagnosis. However, even after review, atypia was considered sufficiently worrying to be reported as a suspicion of malignancy in 7% of cases.
Personal commentaryExternal quality assessment (EQA) in gynaecological cytology: radical rethinking required?
Authors: Slater D. N. 
Published: March 2003

Accepted for publication 19 February 1999THE PASTThe value of EQA in pathology, including proficiency testing in gynaecological cytology, has been the subject of much recent lively debate1–6. In summary, the proven role of EQA in the monitoring of personal performance and ability is still uncertain. Furthermore, its potential to prevent critical incidents remains purely speculative. Also, whether EQA would be better replaced, for some or all professional groups, by other methods of quality assurance is unknown. Similarly, whether EQA can justify the considerable professional time, effort and expense involved has not been resolved.THE PRESENTNot surprisingly, events at Kent & Canterbury Hospitals abruptly halted much of the debate about the foregoing issues7. Indeed, as a direct consequence of this and other incidents, the NHS Executive stipulated unilaterally that EQA is now mandatory within the NHS Cervical Screening Programme (CSP)8 and reinforced the necessity for all qualified laboratory staff to participate8–10. A surprise, however, was the Executive's enlightened comments on EQA. First, and of greatest significance, that the principal function of EQA in pathology is to improve standards and advance quality through personal education. Second, that EQA should be seen to complement other QA systems for the early identification of potential problems which might affect patient care. Third, that the identification of individual poor performance through EQA will be exceptional and in essence is a by‐product of the basic educational exercise. The latter conclusion was drawn, as far as one can judge, from previous experience with the NHS Breast Screening Programme (NHSBSP) EQA.THE FUTURE—PERSONAL SUGGESTIONS FOR OPEN DEBATE
Analysis of proliferating cell fraction determined by monoclonal antibody to M1‐subunit ribonucleotide reductase and Ki‐67 in relation to p53 protein expression in fine‐needle aspirates from non‐Hodgkin's lymphomas
Authors: Sviatoha V. , Tani E. , Rassidakis G. , Tribukait B. , Kleina R. , Skoog L. 
Published: March 2003

Analysis of proliferating cell fraction determined by monoclonal antibody to M1‐subunit ribonucleotide reductase and Ki‐67 in relation to p53 protein expression in fine‐needle aspirates from non Hodgkin's lymphomasThe purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1‐R‐R to M1‐subunit ribonucleotide reductase and with MIB‐1 to Ki‐67 antigen in relation to p53 protein expression in fine needle aspirates from B‐cell non‐Hodgkin's lymphomas.One hundred and thirty‐seven cases, previously diagnosed and sub‐typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M‐1 subunit ribonucleotide reductase (M1‐R‐R), Ki‐67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations.There was a good correlation (r = 0.72) between Ki‐67 and M1‐R‐R positive cell fraction in both high and low grade lymphomas. High‐grade lymphomas had a median percentage of M1‐R‐R/MIB‐1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1‐R‐R/MIB‐1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1‐R‐R/MIB‐1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1‐R‐R and MIB‐1 was higher than in p53 negative cases, but the difference was not statistically significant.The results show that cytospin material obtained by fine needle aspiration and stored at −70 °C for years can be used reliably for both peroxidase‐avidin‐biotin and three‐step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1‐R‐R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki‐67 antibody.However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non‐Hodgkin's lymphoma which indicates that they may contribute different prognostic information.
How predictive is a cervical smear suggesting invasive squamous cell carcinoma?
Authors: Johnson S. J. , Wadehra V. 
Published: March 2003

How predictive is a cervical smear suggesting invasive squamous cell carcinoma? Features have been described in severely dyskaryotic cervical smears that suggest frankly invasive or microinvasive squamous cell carcinoma. These are reported in three separate categories in our department. The aim of the current study was to assess the positive predictive value of these categories for invasive disease on histology. All smears reported in these categories over a five year period were correlated with the histology results. 527 smears were assessed. The positive predictive value of a smear suggesting frank invasion was 55.7% for all invasive squamous carcinomas and 40% for stage IB or above. Smears suspicious of invasion or microinvasion predicted invasive disease in 22.3% and 17.2%, respectively, most carcinomas being stage IA. Invasive squamous cell carcinoma may be predicted to a limited degree by cervical cytology especially when the smear suggests frank invasion.