bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reporting of diabetes on death certificates using data from the UK Prospective Diabetes Study
Authors: Thomason M. J. , Biddulph J. P. , Cull C. A. , Holman R. R. 
Published: September 2005

AbstractAims  To study the effect of age at death, sex, ethnic group, date of death, underlying cause of death and social class on the frequency of reporting diabetes on death certificates in known cases of diabetes.Methods  Data were extracted from certificates recording 981 deaths which occurred between 1985 and 1999 in people aged 45 years or more who participated in the UK Prospective Diabetes Study, to which 23 English, Scottish and Northern Ireland centres contributed. Diabetes (9th revision of the International Classification of Diseases; ICD‐9 250) entered on parts 1A−1C or 2A−2C of the death certificate was considered as reporting diabetes. Logistic regression analyses were used to determine independent factors associated with the reporting of diabetes.Results  Diabetes was reported on 42% (419/981) of all death certificates and on 46% (249/546) of those with underlying cardiovascular disease causes. Reporting of diabetes was independently associated on all death certificates with per year of age increase (OR 1.02; 95% CI 1.001–1.04, P = 0.037), underlying cause of death (non‐cardiovascular causes OR 0.76; 95% CI 0.59–0.98, P = 0.035) and social class (classes I–II OR 1.00; class III OR 1.35; 95% CI 0.96–1.89, P = 0.084, classes IV–V OR 1.48; 95% CI 1.05–2.10, P = 0.027). Stratification by age, sex, and underlying cause of death also revealed significant differences in the frequency of reporting diabetes over time.Conclusions  The rate of reporting of diabetes on cardiovascular disease death certificates remains poor. This may indicate a lack of awareness of the importance of diabetes as a risk factor for cardiovascular disease.
Changes in liver tests during 1‐year treatment of patients with Type 2 diabetes with pioglitazone, metformin or gliclazide
Authors: Belcher G. , Schernthaner G. 
Published: September 2005

AbstractAims  Patients with Type 2 diabetes are at increased risk of liver damage. Therefore, it is of particular importance to investigate the hepatic effects of drugs used to treat such patients.Methods  Liver testing results performed in four 1‐year, randomized, double‐blind studies comparing effects of pioglitazone, metformin or a sulphonylurea, gliclazide, in the treatment of over 3700 patients with Type 2 diabetes have been analysed.Results  Pioglitazone caused reductions in mean levels of hepatic enzymes of between 3 and 18%, whilst gliclazide caused small increases of between 3 and 13%. Metformin treatment showed either small mean increases or decreases. More patients receiving pioglitazone had liver tests within the normal range at the end of treatment (≥ 87%) compared with patients receiving metformin (≥ 80%) or gliclazide (≥ 75%). Slightly fewer patients with pioglitazone than with comparators showed a large increase (> 3 upper limit of normal) in alanine aminotransferase levels at any time during treatment (pioglitazone 0.9%, metformin 1.9%, gliclazide 1.9%).Conclusions  During pioglitazone treatment there is a reduction in liver enzyme levels. Although the mechanism of this effect is not clear, the results demonstrate potential beneficial effects on the liver during treatment of patients with Type 2 diabetes with pioglitazone.
Increases in body mass index, even within non‐obese levels, raise the risk for Type 2 diabetes mellitus: a follow‐up study in a Japanese population
Authors: Nagaya T. , Yoshida H. , Takahashi H. , Kawai M. 
Published: September 2005

AbstractAims  Obesity, the strongest risk factor for Type 2 diabetes mellitus, is less prevalent in Japanese than in other populations. We investigated the effects of body mass index (BMI, kg/m2) on the incidence of diabetes mellitus in a Japanese population.Methods  A follow‐up study in 16 829 men and 8370 women who were apparently healthy at baseline (age 30–59 years, BMI 14.9–43.2 kg/m2). Incident diabetes mellitus was identified by ‘fasting serum glucose ≥ 7.00 mmol/l (126 mg/dl)’ and/or ‘under medical treatment for diabetes mellitus’. Hazard ratio, as an index for risk ratio, for incident diabetes mellitus according to BMI was estimated using Cox's proportional hazard models. Baseline age, smoking, drinking, exercise and education were computed as confounders.Results  During mean follow‐up periods of 7.4 years for men and 7.1 years for women, 869 men and 224 women had incident diabetes mellitus. Although the subjects were averagely non‐obese [mean (sd) BMI 23.1 (2.6) kg/m2 for men, 22.3 (2.7) kg/m2 for women], hazard ratio for incident diabetes mellitus increased in parallel with increases in BMI. Multivariate‐adjusted hazard ratios (95% confidence intervals) for increases in BMI of 1 kg/m2 were 1.26 (1.24, 1.29) for men and 1.24 (1.20, 1.29) for women.Conclusion  BMI, even within the non‐obese level, is a dose‐dependent risk factor for diabetes mellitus in middle‐aged Japanese. Increases in BMI of 1 kg/m2 (= body‐weight gain of 2.4–2.9 kg) may raise the risk by about 25%.
Nurse case manager effectiveness and case load in a large clinical practice: implications for workforce development
Authors: Wilson C. , Curtis J. , Lipke S. , Bochenski C. , Gilliland S. 
Published: September 2005

AbstractAims  Description of nurse case management experiences across different settings and patient populations is needed to define critical elements of the intervention and to help develop a workforce capable of responding to the growing diabetic population.Methods  In a clinic providing services to American Indian and Alaska Native people, a retrospective cohort design was used to assess outcomes of patients who did and did not receive case management services and to quantify the case load of a team of four nurse case managers.Results  Patients with nurse case managers were more likely to have an eye examination [OR 2.9, 95% CI (2.1, 3.8)], diet and exercise instruction by a registered dietitian [OR 2.8, 95% CI (1.9, 4.1)], self monitor blood glucose [OR 2.1, 95% CI (1.5, 3.1)], dental examination [OR 1.7, 95% CI (1.3, 2.3)], foot examination [OR 1.6, 95% CI (1.2, 2.1)], and nephropathy screening [OR 1.6, 95% CI (1.2, 2.1)]. After adjustment for type of treatment, initial HbA1c, and diet instruction by a registered dietitian, the change in HbA1c remained significantly greater among those patients with a case manager than in those without (−0.52 units with vs. −0.17 units without, P < 0.006). The case load used to achieve this outcome averaged one nurse case manager per 365 patients.Conclusions  In this setting, a case management team comprised of four nurses with varying degrees of clinical experience was effective in improving adherence with diabetes services and had a favourable effect on short‐term glucose control trends.
β‐cell preservation: a potential role for thiazolidinediones to improve clinical care in Type 2 diabetes
Authors: Leiter L. A. 
Published: September 2005

AbstractType 2 diabetes is caused by progressively increasing insulin resistance coupled with deteriorating β‐cell function, and there is a growing body of evidence to suggest that both of these defects precede hyperglycaemia by many years. Several studies have demonstrated the importance of maintaining β‐cell function in patients with Type 2 diabetes. This review explores parameters used to indicate β‐cell dysfunction, in Type 2 diabetes and in individuals with a predisposition to the disease. A genetic element undoubtedly underlies β‐cell dysfunction; however, a number of modifiable components are also associated with β‐cell deterioration, such as chronic hyperglycaemia and elevated free fatty acids. There is also evidence for a link between pro‐inflammatory cytokines and impairment of insulin‐signalling pathways in the β‐cell, and the potential role of islet amyloid deposition in β‐cell deterioration continues to be a subject for debate. The thiazolidinediones are a class of agents that have demonstrated clinical improvements in indices of β‐cell dysfunction and have the potential to improve β‐cell function. Data are accumulating to show that this therapeutic group offers a number of advantages over traditionally employed oral agents, and these data demonstrate the growing importance of thiazolidinediones in Type 2 diabetes management.
The effect of manipulation of basal pulsatile insulin on insulin action in Type 2 diabetes
Authors: Au S. , Courtney C. H. , Ennis C. N. , Sheridan B. , Atkinson A. B. , Bell P. M. 
Published: September 2005

AbstractAim  Disordered insulin pulsatility is associated with insulin resistant states including Type 2 diabetes. However, whether abnormal basal insulin pulses play a role in the pathogenesis of insulin resistance or are simply an associated feature remains undetermined. We investigated this relationship further by studying the effect of overnight (10 h) pulsatile insulin infusion on subsequent insulin sensitivity.Methods  We studied 17 Type 2 diabetic patients who underwent one of two protocols. In protocol A (10 patients) on two separate nights we infused insulin 0.1 mU/kg/min either in a constant infusion or in pulses every 13 min. Octreotide (0.43 µg/kg/h) was given to suppress endogenous insulin secretion and physiological replacement of glucagon (30 ng/kg/h) administered. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp (2 mU/kg/min) next morning. In protocol B (seven patients), we employed the same experimental procedure but used a basal insulin infusion rate of 0.09 mU/kg/min in 7‐min or 13‐min pulses.Results  Appropriate pulse patterns were confirmed in each protocol. In protocol A, after overnight infusions, glucose infusion rates required to maintain euglycaemia at steady state hyperinsulinaemia were similar (33.9 ± 5.2 vs. 31.2 ± 4.1 µmol/kg/min; P = NS). In protocol B, after overnight infusions the glucose infusion rates required during hyperinsulinaemia were significantly lower during 7‐min pulses (39.9 ± 5.7 vs. 44.7 ± 5.6 µmol/kg/min; P < 0.05).Conclusion  There was no demonstrable priming effect derived from overnight pulsatile insulin compared with constant insulin infusion on subsequent insulin sensitivity in Type 2 diabetic subjects. The failure of 7‐min pulses to exhibit an advantageous effect over 13‐min pulses raises questions about the natural frequency of basal insulin pulses and their biological effect.
High prevalence and severity of cardiac autonomic neuropathy in Vietnamese diabetic patients
Authors: N’Guyen Thi N. , Paries J. , Attali J. R. , Valensi P. 
Published: September 2005

AbstractAims  Malnutrition is frequent in Vietnamese people and may influence cardiac autonomic neuropathy (CAN). The aim of the present study was to investigate cardiac autonomic function in healthy subjects living in Vietnam and the prevalence of CAN in Vietnamese diabetic patients.Methods  One hundred and five diabetic patients (BMI = 19.8 ± 0.3 kg/m2), 50 Type 1 and 55 Type 2, living in Hué (Vietnam) were selected and compared with 60 non‐diabetic healthy Vietnamese controls (BMI = 20.8 ± 0.2 kg/m2) and also European controls. CAN function was evaluated by five standardized tests: three tests for heart rate variations (HRV) which depend mainly on parasympathetic activity, and two tests for blood pressure (BP) response which depend mainly on sympathetic activity.Results  With age taken into account, 41 of the 60 Vietnamese controls had at least mild CAN, as defined by one abnormal test for HRV when compared with the European control series, and 11 of them had two or three abnormal tests. Among the Vietnamese control men, those with abnormal HRV had lower BMI than those without (P = 0.036). Seven Vietnamese controls had postural hypotension and 16 had an abnormal BP response to the handgrip test. Compared with the Vietnamese controls, 71 diabetic patients (67.6%), 40 Type 1 and 31 Type 2, had at least mild CAN, 37 of them had two or three abnormal HRV tests, and 56 diabetic patients (53.3%) had an abnormal BP response to the sympathetic tests. Abnormal HRV were associated with significantly lower BMI, waist and hip circumferences, longer diabetes duration and higher fasting blood glucose. In the logistic regression analyses, abnormal HRV were associated significantly with duration of diabetes and BMI in patients with Type 2 diabetes.Conclusions  Cardiac autonomic dysfunction is frequent in normal Vietnamese subjects. CAN appears to be a more frequent complication of diabetes in Vietnam than in Western countries and diabetic parasympathetic dysfunction is frequently associated with sympathetic disorders. This confirms the deleterious effect a poor nutritional state has on cardiac autonomic function.
Pioglitazone initiation and subsequent hospitalization for congestive heart failure
Authors: Karter A. J. , Ahmed A. T. , Liu J. , Moffet H. H. , Parker M. M. 
Published: September 2005

AbstractAims  Thiazolidinediones (TZD) have been associated with an expansion in plasma volume and the development of peripheral oedema. A recent study reported an association between the use of TZDs and development of congestive heart failure (CHF). The objective of this study was to determine if short‐term use of pioglitazone, a TZD, is associated with increased risk of admission to hospital because of CHF in a well‐characterized, community‐based cohort of Type 2 diabetic patients without prevalent CHF.Methods  A cohort study of all patients in the Kaiser Permanente Medical Care Program with Type 2 diabetes (Kaiser Permanente Northern California Diabetes Registry) who initiated any diabetes pharmacotherapy (n = 23 440) between October 1999 and November 2001. Only patients initiating single new therapies (‘new users’) were included to reduce confounding and create mutually exclusive exposure groups. We constructed Cox proportional hazards models (with sulphonylureas initiators specified as the reference group) to evaluate the impact of initiating new diabetes therapies on time‐to‐incident admission to hospital because of CHF, defined by primary hospital discharge diagnosis.Results  Patients initiated pioglitazone (15.2%), sulphonylureas (25.3%), metformin (50.9%), and insulin (8.6%) alone, or as additions to pre‐existing or maintained therapies. Three hundred and twenty admissions for CHF were observed during the follow‐up (mean 10.2 months) after drug initiation. Relative to patients initiating sulphonylureas, there were no significant increases in the incidence of hospitalization for CHF in those initiating pioglitazone [hazard ratio (HR) = 1.28; 95% confidence interval (CI): 0.85–1.92] after adjusting for demographic, behavioural and clinical factors. There was a significantly higher incidence among those initiating insulin (HR = 1.56; 95% CI: 1.00–2.45) and lower incidence among those initiating metformin (HR = 0.70; 95% CI: 0.49–0.99).Conclusions  This study of patients with Type 2 diabetes failed to find evidence that short‐term pioglitazone use was associated with an elevated risk of hospitalization for CHF relative to the standard, first‐line diabetes therapy.
Learning from the experts: people with learning difficulties training and learning from each other*
Authors: Weeks Louise , Shane Chris , MacDonald Fiona , Hart Craig , Smith Roger 
Published: September 2005

SummaryThis article is about a training project run by Central England People First (CEPF). CEPF has been doing workshops, conferences and other training for over 10 years. It seemed like a good idea to help other people with learning difficulties to learn how to be trainers. This would help them to speak out about their lives and the services they want. CEPF asked the Department of Health for some money to design a ‘training for trainers’ programme, and try it out. The Department of Health agreed, and CEPF set up the National User Training Development Project. The training team designed a 2‐day programme, and asked people in different parts of the country to try it out. Eight organizations agreed, including a care village, another People First group and two social services departments. Eighty people with learning difficulties and support people took part. The project team told them about what training is for, and how to organize it. They also had the chance to try out their own ideas. They practiced ‘role plays’, ‘speaking up’, doing quizzes and using video recorders. At the end, the people who took part filled in evaluation sheets, so that the team could find out if the training was useful. Most people said that they had enjoyed it, and that they had learned something. At the end of this project, we think we have learnt two things:1.  People with learning difficulties can be good trainers, because they are experts about services and the things that are important in their lives.2. Using training can be a good way of helping people with learning difficulties to speak out about how they want to be treated.
Distinct mechanisms of neuronal apoptosis are triggered by antagonism of Bcl‐2/Bcl‐x(L) versus induction of the BH3‐only protein Bim
Authors: Zimmermann Angela K. , Loucks F. Alexandra , Le Shoshona S. , Butts Brent D. , Florez‐McClure Maria L. , Bouchard Ron J. , Heidenreich Kim A. , Linseman Daniel A. 
Published: September 2005

AbstractPrimary cerebellar granule neurons (CGNs) require depolarizing extracellular potassium for their survival. Removal of depolarizing potassium triggers CGN apoptosis that requires induction of Bim, a BH3‐only Bcl‐2 family member. Bim is classically thought to promote apoptosis by neutralizing pro‐survival Bcl‐2 proteins. To determine if this is the principal function of Bim in CGNs, we contrasted Bim‐mediated apoptosis to neuronal death induced by HA14‐1, a BH3‐domain mimetic that antagonizes Bcl‐2 and Bcl‐x(L). HA14‐1 elicited CGN apoptosis characterized by caspase 3 and 9 activation, cytochrome c release, conformational activation of Bax, and mitochondrial depolarization. HA14‐1 provoked CGN apoptosis in the absence of Bim induction and negative regulators of Bim transcription did not prevent HA14‐1‐induced cell death. However, the antioxidant glutathione and its precursor, N‐acetyl‐l‐cysteine, suppressed HA14‐1‐induced apoptosis. Similarly, apoptosis induced by either a structurally distinct Bcl‐2/Bcl‐x(L) inhibitor (compound 6) or Bcl‐2 antisense oligonucleotides was diminished by glutathione. In contrast, antioxidants had no effect on CGN apoptosis provoked by either removal of depolarizing potassium or overexpression of a GFP–Bim fusion protein, two models of Bim‐dependent death. These data show that antagonism of Bcl‐2/Bcl‐x(L) function elicits oxidative stress‐dependent CGN apoptosis that is mechanistically distinct from Bim‐mediated cell death. These results further indicate that, although Bcl‐2/Bcl‐x(L) antagonism is sufficient to induce neuronal apoptosis, Bim likely promotes neuronal death by interacting with additional proteins besides Bcl‐2/Bcl‐x(L).
Dopaminergic transmission in STOP null mice
Authors: Brun Philippe , Bégou Mélina , Andrieux Annie , Mouly‐Badina Laurence , Clerget Magali , Schweitzer Annie , Scarna Hélène , Renaud Bernard , Job Didier , Suaud‐Chagny Marie‐Françoise 
Published: September 2005

AbstractNeuroleptics are thought to exert their anti‐psychotic effects by counteracting a hyper‐dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule‐stabilizing protein and which display neuroleptic‐sensitive behavioural disorders. Dopamine transmission was investigated using both behavioural analysis and measurements of dopamine efflux in different conditions. Compared to wild‐type mice in basal conditions or following mild stress, STOP null mice showed a hyper‐locomotor activity, which was erased by neuroleptic treatment, and an increased locomotor reactivity to amphetamine. Such a behavioural profile is indicative of an increased dopaminergic transmission. In STOP null mice, the basal dopamine concentrations, measured by quantitative microdialysis, were normal in both the nucleus accumbens and the striatum. When measured by electrochemical techniques, the dopamine efflux evoked by electrical stimulations mimicking physiological stimuli was dramatically increased in the nucleus accumbens of STOP null mice, apparently due to an increased dopamine release, whereas dopaminergic uptake and auto‐inhibition mechanisms were normal. In contrast, dopamine effluxes were slightly diminished in the striatum. Together with previous results, the present study indicates the association in STOP null mice of hippocampal hypo‐glutamatergy and of limbic hyper‐dopaminergy. Such neurotransmission defects are thought to be central to mental diseases such as schizophrenia.
Suppression of glial glutamine release to the extracellular fluid studiedin vivoby NMR and microdialysis in hyperammonemic rat brain
Authors: Kanamori Keiko , Ross Brian D. 
Published: September 2005

AbstractRelease of glial glutamine (GLN) to the extracellular fluid (ECF), mainly mediated by the bidirectional system N transporter SN1, was studiedin vivoin hyperammonemic rat brain, using15N‐nuclear magnetic resonance (NMR) to monitor intracellular [5‐15N]GLN and microdialysis/gradient1H‐15N heteronuclear single‐quantum correlation NMR to analyse extracellular [5‐15N]GLN. GLNECFwas elevated to 2.4 ± 0.2 mmafter 4.5 h of intravenous ammonium acetate infusion. The [GLNi]/[GLNECF] ratio (i = intracellular) was 9.6 ± 0.9, compared with 17–20 in normal brain. GLNECFthen decreased substantially att = 4.9 ± 0.1 h. Comparison of the time‐courses of intra‐ and extra‐cellular [5‐15N]GLN strongly suggested that the observed decrease reflects partial suppression of glial GLN release to ECF. Suppression also followed elevation of GLNECFto 1.9 mm, resulting in a [GLN]i/[GLNECF] ratio of 8.4, upon perfusion ofα‐(methylamino)isobutyrate which inhibits neuronal uptake of GLNECFmediated by sodium‐coupled amino acid transporter (SAT). The results provide first evidence for bidirectional operation of SN1in vivo, and clarify the effect of transmembrane GLN gradient on glial GLN release at physiological Na+gradient. Implications of the results for SN1 as an additional regulatory site in the glutamine/glutamate cycle and utility of this approach for examining the role of GLN in an experimental model of fulminant hepatic failure are discussed.
The tissue‐specific methylation of the human Tyrosine Hydroxylase gene reveals new regulatory elements in the first exon
Authors: Arányi Tamás , Faucheux Baptiste A. , Khalfallah Olfa , Vodjdani Guilan , Biguet Nicole Faucon , Mallet Jacques , Meloni Rolando 
Published: September 2005

AbstractThe methylation status of CpG dinucleotides located in or near regulatory elements affects gene expression. The CpG‐rich sequence located outside the 5′ promoter region of the human Tyrosine Hydroxylase (TH) gene appears to influence the functional effect of the adjacent intronic HUMTH01 microsatellite. In order to identify new regulatory elements in this region acting on gene expression, the methylation profile of the TH CpG island was investigated using the bisulfite sequencing method. The overall methylation level of this region is correlated to TH‐expressing and non‐expressing status in cell lines and DNA demethylation treatment with 5‐azacytidine increased TH expression. Moreover, in a homogeneous background of methylated CpGs, a single CpG in the first exon of the gene is constantly either unmethylated or methylated in, respectively, TH‐expressing or non‐expressing cell lines, tissues and single cells. Further analysis ascertained that this CpG is contained in a sequence characterized by putative binding sites for the AP2, Sp1 and KAISO factors. Characterization of this sequence shows that these factors specifically bind their respective sites. Finally, the binding of KAISO, a transcriptional repressor, is conditioned by the methylation of this sequence, which may, thus, participate in the regulation of TH gene expression according to its methylation pattern.