bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of the relationship between adult height and health‐related quality of life in the general UK population
Authors: Christensen T. L. , Djurhuus C. B. , Clayton P. , Christiansen J. S. 
Published: June 2007

SummaryObjective  Short stature has previously been shown to influence several social factors during childhood and adult life. However, limited data exist to determine the influence of short stature on health‐related quality of life (HRQoL) because of underpowered studies and the fact that children find questionnaires very difficult to complete. The objective of this study was to examine the influence of height on HRQoL for the general adult population in the UK.Design  The 2003 Health Survey for England (HSE03), commissioned by the Department of Health, provides a random general population sample for the population living in private households in England. Observations for 14 416 adults (aged > 18 years) were included in the analysis.Measurements  The survey involved a questionnaire‐based interview and a nurse visit, where measurements and blood samples were taken. HRQoL was measured using the EQ‐5D questionnaire. Social class (I–V) was derived according to definitions from UK National Statistics. Height was converted from centimetres to height standard deviation scores (HSDS).Results  Mean EQ‐5D scores were lower in subjects with greater height deficit than in taller subjects. Three significantly different subgroups were identified using an analysis of variance (anova). The first subgroup ‘HSDS ≤ –2·0’ had significantly lower EQ‐5D scores compared with the second group ‘–2·0 > HSDS ≤ 0’ and the third group ‘HSDS > 0’. Multivariate linear regression analysis showed significant correlations between height and HRQoL, such that an increase in height of 1 HSDS predicts an improvement in EQ‐5D score of 6·1% for subjects shorter than –2·0 HSDS. Social class was a significant predictor of HRQoL in taller, but not in shorter, subjects.Conclusion  The results of this study demonstrate that height in adult life is correlated with HRQoL and that short stature in adult life may be associated with a significant reduction in HRQoL.
Predictors of remission of hyperprolactinaemia after long‐term withdrawal of cabergoline therapy
Authors: Colao Annamaria , Di Sarno Antonella , Guerra Ermelinda , Pivonello Rosario , Cappabianca Paolo , Caranci Ferdinando , Elefante Andrea , Cavallo Luigi M. , Briganti Francesco , Cirillo Sossio , Lombardi Gaetano 
Published: June 2007

SummaryBackground  Remission rates of 76, 69·5 and 64·3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2–5 years after cabergoline (CAB) withdrawal.Objective  To report the estimated recurrence rate at 24–96 months after CAB withdrawal and indicate predictors of disease remission.Design  Observational, analytical, prospective.Patients  Of 381 previously untreated de novo patients with hyperprolactinaemia, 221 (58%) (173 women, 48 men; 27 with NTH, 115 with micro‐, and 79 with macroprolactinoma) were studied.Measurements  Using multiple regression analysis the diagnostic accuracy of nadir PRL levels (t = 7·6, P < 0·0001) and nadir maximal tumour diameter at CAB withdrawal (t = 3·9, P < 0·001) was analysed using receiver operating characteristic (ROC) curves.Results  The recurrence of hyperprolactinaemia was 25·9, 33·9 and 53·1% in patients with NTH, micro‐ or macroprolactinoma, respectively. To predict the last PRL level after withdrawal, the optimum cut‐off of nadir PRL levels at withdrawal was 162 mU/l (5·4 µg/l) [sensitivity (95% CI) 76% (67–84%), specificity 65% (51–77%)] and that of nadir maximal tumour diameter was 3·1 mm [sensitivity 52% (41–63%), specificity 86% (79–91%)]. The patients achieving both nadir PRL levels ≤ 162 mU/l and maximal tumour diameter ≤ 3·1 mm (n = 111) at CAB withdrawal had a significantly lower Kaplan–Meier estimate of recurrence of hyperprolactinaemia (20%) at 24–96 months than those who did not fulfil any of these criteria [(n = 38) 90%; P < 0·0001]. Patients achieving nadir PRL levels ≤ 162 mU/l (n = 26) or maximal tumour diameter ≤ 3·1 mm during CAB treatment (n = 46) had an estimated recurrence rate of hyperprolactinaemia of 50 and 56%, respectively.Conclusion  Persistent remission of hyperprolactinaemia without any evidence of tumour re‐growth after 24–96 months of CAB withdrawal occurred in the majority of patients with NTH and microprolactinoma and in about half of those with macroprolactinoma. Nadir PRL levels and maximal tumour diameter at CAB withdrawal of ≤ 162 mU/l and ≤ 3·1 mm predicted remission of hyperprolactinaemia in 80% of patients.
Oestrogen stimulates endothelial progenitor cells via oestrogen receptor‐α
Authors: Foresta Carlo , Zuccarello Daniela , Biagioli Andrea , De Toni Luca , Prana Elisa , Nicoletti Valentina , Ambrosini Guido , Ferlin Alberto 
Published: June 2007

SummaryContext  Oestrogens play an important protective role on the vascular system. The endothelial cell layer is a direct target for these hormones, and expresses at least two oestrogen receptors, ER‐α and ER‐β. Recent studies have shown that vascular healing is significantly modulated by circulating bone marrow‐derived cells. A subset of these stem cells, endothelial progenitor cells (EPCs), have recently been described as a population of pluripotent cells within the peripheral blood capable of differentiating into endothelial cells.Objective  In the present study we investigated the expression of ER‐α and ER‐β on human EPCs and the effect that oestrogens have on the function of EPCs in vitro.Methods  EPCs were isolated and cultured from healthy donors. RT‐PCR, western blotting and immunohistochemistry were used to assess expression of ER‐α and ER‐β. Proliferation and CFU assays were used to assess the response of EPCs to different doses of 17,β‐oestradiol.Main outcome measures  Expression of ER‐α and ER‐β in EPCs, and the effect of 17,β‐oestradiol on proliferation of EPCs.Results  Human EPCs express ER‐α mRNA and protein. 17,β‐oestradiol increases proliferation of EPCs and CFU in a dose‐dependent manner.Conclusions  Human EPCs express ER‐α but not ER‐β, and oestrogens can stimulate the proliferation of these cells in vitro. Oestrogens exert these effects at concentrations that are usually reached during stimulation for in vitro fertilization in women, and therefore further studies are needed to clarify the clinical significance of these effects.
Mutations in GCK and HNF‐1α explain the majority of cases with clinical diagnosis of MODY in Spain
Authors: Estalella Itziar , Rica Itxaso , De Nanclares Guiomar Perez , Bilbao Jose Ramon , Vazquez Jose Antonio , San Pedro Jose Ignacio , Busturia Maria Angeles , Castaño Luis ,   Spanish MODY Group
Published: June 2007

SummaryObjective  The aim of this study was to group patients with MODY (maturity‐onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics.Patients and methods  Molecular analysis of GCK (MODY2), HNF‐1α (MODY3), HNF‐4α (MODY1) and HNF‐1β (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9·9 ± 5·2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups.Results  Seventy‐six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF‐1α mutations, and a large genomic rearrangement in HNF‐1β was found in a family. No alteration was found in HNF‐4α. Thus, relative frequencies in the group studied were 80% MODY2, 8·5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9·4 ± 5·4 years vs. 12·7 ± 4·6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2·96 ± 0·44 kg vs. 3·40 ± 0·67 kg).Conclusion  Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF‐1α(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment.
A clinical trial on absorption andN‐acetylation of oral and rectal mesalazine
Authors: Dilger K. , Trenk D. , Rössle M. , Cap M. , Zähringer A. , Wacheck V. , Remmler C. , Cascorbi I. , Kreisel W. , Novacek G. 
Published: June 2007

AbstractBackground Mesalazine (5‐ASA) is a standard treatment for ulcerative colitis. Extent of absorption andN‐acetylation determine systemic exposure to 5‐ASA, and are thereby relevant for the safety of the treatment. The aim of the study was to compare absorption andN‐acetylation of 5‐ASA following rectal or oral drug administration. Healthy subjects were compared to patients with ulcerative colitis to evaluate the impact of chronic inflammation of colorectal mucosa on disposition of 5‐ASA.Materials and methods First, 12 healthy adults were randomized to receive 2 g of 5‐ASA by each of four different formulations: oral delayed release granules, 30 mL enema, 60 mL rectal foam, and 120 mL rectal foam. Second, 12 patients with active ulcerative colitis received 60 mL rectal foam. Pharmacokinetic analysis was performed by determination of 5‐ASA and its acetylated, pharmacologically inactive metabolite (Ac‐5‐ASA) in plasma and urine.Results First, systemic exposure to 5‐ASA was markedly lower after rectal drug administration as compared to oral dosing (P < 0·001; e.g. median relative bioavailability of 60 mL rectal foam: 36%). Second,N‐acetylation of rectal 5‐ASA was lower in patients than in healthy subjects [area under the curve (AUC) ratio Ac‐5‐ASA/5‐ASA: 1·6 ± 0·5 vs. 2·3 ± 0·4, mean ± SD,P < 0·01]. High peak plasma concentrations of 5‐ASA were correlated with high microscopic disease activity (r = 0·67,P < 0·05).Conclusions Rectal delivery of 5‐ASA results in low systemic drug exposure with potentially reduced toxicity in comparison with oral drug administration. Chronic inflammation of colorectal mucosa might be a relevant source of variability in pharmacokinetics of 5‐ASA.
Lifestyle intervention in individuals with normal versus impaired glucose tolerance
Authors: Schäfer S. , Kantartzis K. , Machann J. , Venter C. , Niess A. , Schick F. , Machicao F. , Häring H.‐U. , Fritsche A. , Stefan N. 
Published: June 2007

AbstractBackground  Lifestyle intervention is effective in the prevention of type 2 diabetes in individuals with impaired glucose tolerance (IGT). It is currently unknown whether it has beneficial effects on metabolism to a similar extent, in individuals with normal glucose tolerance (NGT) compared to individuals with IGT.Materials and methods  Data from 181 subjects (133 with NGT and at risk for type 2 diabetes and 48 with IGT) who participated in the Tuebingen Lifestyle Intervention Program with increase in physical activity and decrease in caloric intake were included into this study. Body fat distribution was quantified by whole‐body magnetic resonance (MR) tomography and liver fat and intramyocellular fat by 1H‐MR spectroscopy. Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT).Results  After 9 ± 2 months of follow‐up, the diagnosis of IGT was reversed in 24 out of 48 individuals. Only 14 out of 133 participants with NGT developed IGT. Body weight decreased in both groups by 3% (both P < 0·0001). Two‐hour glucose concentrations during an OGTT decreased in individuals with IGT (–14%, P < 0·0001) but not with NGT (+2%, P = 0·66). Insulin sensitivity increased both in individuals with IGT (+9%, P = 0·04) and NGT (+17%, P < 0·0001). Visceral fat (–8%, P = 0·006), liver fat (–28%, P < 0·0001) and intramyocellular fat (–15%, P = 0·006) decreased in participants with IGT. In participants with NGT these changes were significant for visceral fat (–16%, P < 0·0001) and liver fat (–35%, P < 0·0001).Conclusions  Moderate weight loss under a lifestyle intervention with reduction in total, visceral and ectopic fat and increase in insulin sensitivity improves glucose tolerance in individuals with IGT but not with NGT. In individuals with NGT, the beneficial effects of a lifestyle intervention on fat distribution and insulin sensitivity possibly prevent future deterioration in glucose tolerance.
Placental immaturity and hyperinsulinaemia in full‐term newborns
Authors: Rodríguez‐Morán M. , Levario‐Carrillo M. , González J. L. , Sánchez‐Ramírez B. , Martínez‐Aguilar G. , Guerrero‐Romero F. 
Published: June 2007

AbstractBackground  Evidence from large studies suggests that low birthweight is a risk factor for cardiovascular disease and glucose metabolism disorders in adulthood, but the physiological mechanisms involved in intrauterine growth conditioning low birthweight are not completely understood. The objectives of this study were to determine whether placental immaturity (PI), defined as the lower quartile of placental maturity index (PMI), is associated to hyperinsulinaemia at birth and to identify the risk factors associated with PI.Materials and methods  Cross‐sectional study conducted at medical research units of two Mexican general hospitals. A total of 272 full‐term newborns with gestational age ≥ 38 and < 41 weeks were allocated into the corresponding group according to the quartile distribution of PMI. Data from the lower (PMI < 13·3) and higher quartile (PMI ≥ 24·3) were compared. The PMI was estimated by dividing the number of epithelial plates by the average thickness of the epithelial plate. Serum measures included cord glucose and insulin levels of the newborns at birth.Results  A total of 74 (27·2%) children had hyperinsulinaemia at birth, of them 47 (63·5%) with PI. The adjusted multiple regression analysis showed a strong association between PI and hyperinsulinaemia at birth [odds ratio (OR) 2·6; CI 95% 1·3–4·3). Additional adjusted analysis showed that both mother's age ≤ 16 years (OR 1·75; CI95% 1·2–9·1) and maternal cigarette smoking (OR 2·7; CI95% 1·3–8·9) are associated to PI.Conclusions  The PI is independently associated with hyperinsulinaemia at birth: smoking and mother's age lower than 16 years are risk factors for development of PI.
Novel SDHD germ‐line mutations in pheochromocytoma patients
Authors: Neumayer C. , Moritz A. , Asari R. , Weinhäusel A. , Hölzenbein T. , Kretschmer G. , Niederle B. , Haas O. A. 
Published: June 2007

AbstractBackground  SDHD germ‐line mutations predispose to pheochromocytoma (PCC) and paraganglioma (PGL).Material and methods  The incidence and types of SDHD germ‐line mutations are determined in 70 patients with apparently sporadic adrenal and extra‐adrenal PCC.Results  SDHD sequence variants were identified in the germ line of five patients. Two of three novel mutations were in exon 1 and one in exon 3. One patient had a codon 1 missense mutation (M1K) and a concurrent 3‐bp deletion in intron 1. Three of 10 family members had only the exon 1 mutation, whereas one had only the intron 1 mutation. The other exon 1 mutation resulted from a deletion of nucleotides 28–33 with a 12‐bp in‐frame insertion (c.28_33 del ins TAGGAGGCCCTA). This mutation generated a premature stop codon after codon 9 and was also present in the brother who had a bilateral PCC. The third patient with a carotid body tumour, with an abdominal and a thoracic PGL had a 12‐bp deletion in exon 3 (codons 91–94, c.271_282 del). Her father carried the same mutation and had bilateral carotid body tumours. Two further patients, one with six PGL, carried a previously described H50R polymorphism, whose disease‐specific relevance is currently unclear. The three patients with bona fide SDHD mutations were younger than those without germ‐line mutations.Conclusion  SDHD germ‐line mutations are rare in patients with PCC, but their identification is an important prerequisite for the clinical care and appropriate management of affected individuals and their families.
Patients with macroprolactinaemia: clinical and radiological features
Authors: Donadio F. , Barbieri A. , Angioni R. , Mantovani G. , Beck‐Peccoz P. , Spada A. , Lania A. G. 
Published: June 2007

AbstractBackground  Macroprolactinaemia may represent a relevant cause of misdiagnosis, unnecessary investigation and inappropriate treatment. The aim of this study was to investigate the clinical and neuroradiological characteristics of patients with and without macroprolactinaemia and to evaluate the impact of macroprolactin determination on the diagnostic work‐up of hyperprolactinaemic patients.Materials and methods  Retrospective analysis in 135 consecutive hyperprolactinaemic patients (111 women and 24 men; mean age 37 ± 11·6 years) whose archived sera were subsequently tested for macroprolactin. Recoveries ≤ 40% after polyethylene glycol precipitation were indicative of macroprolactinaemia.Results  Macroprolactin, entirely explaining biochemical hyperprolactinaemia, was found in 42·2% of patients, a third of whom presented with signs and symptoms of hyperprolactinaemia. Determination of macroprolactin changed the initial diagnosis in a consistent proportion of patients. In particular, idiopathic hyperprolactinaemia, initially diagnosed in 41 patients, was then excluded in 28 of them. Diagnosis of prolactin‐secreting pituitary microadenoma shifted to non‐secreting pituitary microadenoma in 10 of 49 patients, while in all patients with prolactin‐secreting pituitary macroadenoma or hyperprolactinaemia due to stalk deafferentation the presence of macroprolactin was excluded and the initial diagnosis confirmed. Finally, macroprolactin was present in the majority of patients with magnetic resonance imaging (MRI) scans suggestive for primary empty sella (4 of 5 women) or pituitary hyperplasia (12 of 17 women, 3 of 3 men). Collectively, about half of subjects with macroprolactinaemia showed variable MRI abnormalities.Conclusions  The presence of macroprolactin was a relevant cause of misdiagnosis in patients with hyperprolactinaemia. However, due to the unexpected high frequency of pituitary abnormalities observed in the present series, we suggest that the diagnostic algorithm of hyperprolactinaemic states should include both polyethylene glycol precipitation test and MRI imaging.
Complexity of the HVR‐1 quasispecies and disease activity in patients with hepatitis C
Authors: Kumagai N. , Kaneko F. , Tsunematsu S. , Tsuchimoto K. , Tada S. , Saito H. , Hibi T. 
Published: June 2007

AbstractBackground  Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N‐terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR‐1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels.Materials and methods  Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2·5 years by fluorescence single‐strand conformation polymorphism and sequence analysis.Results  There was no significant difference in the changes in the number of quasispecies during the follow‐up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR‐1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression.Conclusion  Our results suggested that the disease activity is not always related to the generation of the HVR‐1 quasispecies complexity.
The 15N‐CPMAS spectra of simazine and its metabolites: measurements and quantum chemical calculations
Authors: Berns A. E. , Bertmer M. , Schäffer A. , Meier R. J. , Vereecken H. , Lewandowski H. 
Published: June 2007

SummaryDFT calculations are a powerful tool to support NMR studies of xenobiotics such as decomposition studies in soil. They can help interpret spectra of bound residues, for example, by predicting shifts for possible model bonds. The described bound‐residue models supported the hypothesis of a free amino side chain already suspected by comparison with the experimental data of the standards. No match was found between the calculated shifts of amide bondings of the amino side chains (free or substituted) and the experimental NMR shifts of a previous study. In the present paper, first‐principles quantum chemical calculations were used to support and check the interpretation of the 15N cross polarization‐magic angle spinning nuclear magnetic resonance (15N‐CPMAS NMR) spectra of simazine and its metabolites. Density functional theory (DFT) calculations were performed using Gaussian 03 and the nuclear magnetic shielding tensors were calculated using the Gauge‐Independent Atomic Orbital (GIAO) method and B3LYP/6–311+G(2d,p) model chemistry. Good agreement was reached between the calculated and measured chemical shifts of the core nitrogens and the lactam and lactim forms of the hydroxylated metabolites could be clearly distinguished. The calculated spectra showed that these metabolites exist preferentially in the lactam form, an important fact when considering the possible interactions of such hydroxylated metabolites with the soil matrix. Although the calculated bound‐residue models in the present study only partly matched the experimental data, they were nevertheless useful in helping to interpret the experimental NMR results of a previous study. To get a better match between the calculated and the measured shifts of the side‐chain nitrogens the calculations need to be further developed, taking into account the influence of neighbouring molecules in the solid state. Altogether, quantum chemical calculations are very helpful in the interpretation of NMR spectra. In the future, they can also be very useful for the prediction of NMR shifts, in particular when it is not possible to measure the metabolites due to a lack of material or in cases where practical experiments cannot be conducted.