bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians
Authors: Bugeja Matthew J , Booth David , Bennetts Bruce , Heard Robert , Rubio Justin , Stewart Graeme 
Published: July 2006

AbstractBackgroundMultiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. It is believed to result from the complex interaction of a number of genes, each with modest effect. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS.MethodsWe conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. After sequencing the chemokine genes in several DNA pools to identify common polymorphisms, 12 candidate single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of Australian MS trio families.ResultsMarginally significant (uncorrected) transmission distortion was identified for four of the SNPs after stratification for several factors. We also identified marginally significant (uncorrected) transmission distortion for haplotypes encompassing theCCL2andCCL11genes, using two independent cohorts, which was consistent with recent reports from another group.ConclusionOur results implicate several chemokines as possibly being associated with MS susceptibility, and given that chemokines and their receptors are suitable targets for therapeutic agents, further investigation is warranted in this region.
Resident-generated versus instructor-generated cases in ethics and professionalism training
Authors: Kon Alexander A 
Published: July 2006

Abstract

Background
The emphasis on ethics and professionalism in medical education continues to increase. Indeed, in the United States the ACGME will require residency programs to include professionalism training in all curricula by 2007. Most courses focus on cases generated by the course instructors rather than on cases generated by the trainees. To date, however, there has been no assessment of the utility of these two case discussion formats. In order to determine the utility of instructor-generated cases (IGCs) versus resident-generated cases (RGCs) in ethics and professionalism training, the author developed an innovative course that included both case formats. The IGCs were landmark cases and cases from the experience of the course instructors, while the RGCs were selected by the residents themselves. Residents were then surveyed to assess the strengths and weaknesses of each format.

Results
Of twenty-two second and third year residents, fourteen completed surveys (response rate 64%). Residents were nearly evenly split in preferring RGCs (38%), IGCs (31%), or not preferring one to the other (31%). 29% stated that they learn more from the RGCs, 21% stated that they learn more from the IGCs, and 50% stated that they did not find a difference in their learning based on format. In general, residents surveyed prefer a mix of formats. Residents tended to find the RGCs more relevant and interesting, and felt the IGCs were necessary to ensure adequate breadth of cases and concepts.

Conclusion
Based on our relatively small sample at a single institution, we believe that educators should consider incorporating both instructor-generated and resident-generated cases in their ethics and professionalism curricula, and should evaluate the utility of such a model at their own institution. Further work is needed to illuminate other potential improvements in ethics and professionalism education.
Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneously
Authors: Lamoureux Jennifer L , Buckner Jane Hoyt , David Chella S , Bradley David S 
Published: July 2006

AbstractRelapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6–8 weeks old) HLA-DQ6αβ8αβ transgenic Aβ0 mice, following immunization with heterologous type II collagen (CII).We present evidence here that transgenic strains expressing the DQ6α8β transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5–6 months and 40–50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis – three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however – more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis.This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis.
Intensive Insulin Therapy in the Intensive Care Unit
Authors: De Block Christophe , Manuel-y-Keenoy Begoña , Van Gaal Luc , Rogiers Peter 
Published: July 2006

OBJECTIVE—Hyperglycemia occurs in most critically ill patients. Using continuous glucose monitoring (CGM), we investigated whether intensive insulin therapy based on discontinuous glucose monitoring can achieve normoglycemia (80–110 mg/dl) in a medical intensive care unit (MICU).
RESEARCH DESIGN AND METHODS—Fifty adults (men/women 31/19, age 62 ± 16 years, nondiabetic/diabetic 30/20, intravenous/subcutaneous insulin 22/28, and Acute Physiology and Chronic Health Evaluation II score 22 ± 7) were prospectively recruited. Forty-eight–hour CGM was performed using a subcutaneous glucose sensor (GlucoDay) and compared with arterial glycemia. Main outcome measures were percent of time in normoglycemia and accuracy/applicability of CGM.
RESULTS—During 48-h CGM, glycemia reached target (80–110 mg/dl) in only 22 ± 18%, was &gt;140 mg/dl in 39 ± 27%, and was &lt;60 mg/dl in 5 ± 10% of the time. Patients on subcutaneous versus intravenous insulin had more glycemia readings &gt;110 mg/dl (P = 0.016). Glycemia was higher in diabetic patients (170 ± 77 vs. 129 ± 35 mg/dl, P = 0.013). BMI was an independent determinant for bad glycemic control (β = 0.73, P &lt; 0.0001). Diabetic state (β = 0.47, P &lt; 0.0001), septic shock (β = 0.22, P = 0.045), sequential organ failure assessment score (β = 0.40, P = 0.001), and use of corticoids (β = 0.28, P = 0.014) and inotropics (β = −0.24, P = 0.035) were independent determinants of insulin dose. GlucoDay values and arterial glycemia correlated well (r = 0.85, P &lt; 0.0001, n = 555 after six-point calibration), with 97% of data falling in regions A and B of error grid analysis. There were no adverse events using GlucoDay.
CONCLUSIONS—GlucoDay, a well-tolerated 48-h CGM system, revealed that normoglycemia was only achieved 22% of the time in MICU patients. Further studies should investigate whether application of CGM to titrate insulin therapy can improve patient outcome.
Clinical Effectiveness of First and Repeat Influenza Vaccination in Adult and Elderly Diabetic Patients
Authors: Looijmans-Van den Akker Ingrid , Verheij Theo J.M. , Buskens Erik , Nichol Kristin L. , Rutten Guy E.H.M. , Hak Eelko 
Published: July 2006

OBJECTIVE—Influenza vaccine uptake remains low among the high-risk group of patients with diabetes, partly because of conflicting evidence regarding its potential benefits. We assessed the clinical effectiveness of influenza vaccination in adults with diabetes and specifically examined potential modification of effect by age and prior influenza vaccine uptake.
RESEARCH DESIGN AND METHODS—The study was part of the Prevention of Influenza, Surveillance and Management (PRISMA) study, a nested case-control study conducted during the 1999–2000 influenza A epidemic, among 75,235 patients from primary care of any age recommended for vaccination. Among 9,238 adult patients with diabetes, 131 cases arose who were either hospitalized for diabetes dysregulation, acute respiratory disease, or cardiovascular disease and 61 cases who died, and we compared them with 1,561 control subjects. We evaluated the effect of (prior) influenza vaccination by means of logistic regression analysis controlling for age, sex, health insurance coverage, prior health care use, medication use, and comorbid conditions.
RESULTS—Vaccination was associated with a 56% reduction in any complication (95% CI 36–70%), a 54% reduction in hospitalizations (26–71%), and 58% reduction in deaths (13–80%). Among study subjects aged 18–64 years, we observed somewhat higher reductions in the occurrence of any complication than among those aged &gt;65 years (72 vs. 39%). In first-time vaccinated subjects, the primary end point was reduced by 47% (0.2–72%), and in those who received vaccination in the year before, the reduction was 58% (4–81%).
CONCLUSIONS—Adults with type 2 diabetes, like other individuals from recognized risk groups, benefit considerably from influenza vaccination, and no difference in vaccine effectiveness was observed between first-time and repeat vaccination.
Systematic Evaluation of the Quality of Randomized Controlled Trials in Diabetes
Authors: Montori Victor M. , Wang Yaqian Grace , Alonso-Coello Pablo , Bhagra Sumit 
Published: July 2006

OBJECTIVE—We sought to systematically ascertain the quality of randomized controlled trials (RCTs) in diabetes.
RESEARCH DESIGN AND METHODS—We identified the 10 most recently published trials as of 31 October 2003 in each of six general medical, five diabetes, and five metabolism and nutrition journals and further enriched our sample with 10 additional RCTs from each of five journals that published the most eligible RCTs in a year. We explored the association between trial characteristics and reporting quality using univariate analyses and a preplanned multivariate regression model.
RESULTS—After excluding redundant reports of included trials and one trial that measured outcomes on the health system and not on patients, we included 199 RCTs: 119 assessed physiological and other laboratory outcomes, 42 assessed patient-important outcomes (e.g., morbidity and mortality, quality of life), and 38 assessed surrogate outcomes (e.g., disease progression or regression, HbA1c, cholesterol). Fifty-three percent were of low methodological quality, as were one-third (36–40%) of trials reporting patient-important or surrogate outcomes and two-thirds (64%) of laboratory investigations. Independent predictors of low quality were nonprofit funding source (odds ratio 3.1 [95% CI 1.5–6.2]), measure of physiological and laboratory outcomes (2.3 [1.2–4.4]), and cross-over design (2.3 [1.1–4.8]), all characteristics of laboratory clinical investigations.
CONCLUSIONS—There is ample room for improving the quality of diabetes trials. To enhance the practice of evidence-based diabetes care, trialists need to pay closer attention to the rigorous implementation and reporting of important methodological safeguards against bias in randomized trials.
Effects of Traditional and Western Environments on Prevalence of Type 2 Diabetes in Pima Indians in Mexico and the U.S.
Authors: Schulz Leslie O. , Bennett Peter H. , Ravussin Eric , Kidd Judith R. , Kidd Kenneth K. , Esparza Julian , Valencia Mauro E. 
Published: July 2006

OBJECTIVE—Type 2 diabetes and obesity have genetic and environmental determinants. We studied the effects of different environments on these diseases in Pima Indians in Mexico and the U.S.
RESEARCH DESIGN AND METHODS—Adult Pima-Indian and non-Pima populations in the Sierra Madre mountains of Mexico were examined using oral glucose tolerance tests and assessments for obesity, physical activity, and other risk factors. Results were compared with those from Pima Indians in Arizona. Both Pima populations were typed for DNA polymorphisms to establish their genetic similarity.
RESULTS—The age- and sex-adjusted prevalence of type 2 diabetes in the Mexican Pima Indians (6.9%) was less than one-fifth that in the U.S. Pima Indians (38%) and similar to that of non-Pima Mexicans (2.6%). The prevalence of obesity was similar in the Mexican Pima Indians (7% in men and 20% in women) and non-Pima Mexicans (9% in men and 27% in women) but was much lower than in the U.S. Pima Indians. Levels of physical activity were much higher in both Mexican groups than in the U.S. Pima Indians. The two Pima groups share considerable genetic similarity relative to other Native Americans.
CONCLUSIONS—The much lower prevalence of type 2 diabetes and obesity in the Pima Indians in Mexico than in the U.S. indicates that even in populations genetically prone to these conditions, their development is determined mostly by environmental circumstances, thereby suggesting that type 2 diabetes is largely preventable. This study provides compelling evidence that changes in lifestyle associated with Westernization play a major role in the global epidemic of type 2 diabetes.
Low Blood Flow Estimates in Lower-Leg Arteries Predict Cardiovascular Events in Japanese Patients With Type 2 Diabetes With Normal Ankle-Brachial Indexes
Authors: Yoshimura Toru , Suzuki Eiji , Egawa Katsuya , Nishio Yoshihiko , Maegawa Hiroshi , Morikawa Shigehiro , Inubushi Toshiro , Hisatomi Akitaka , Fujimoto Kazuma , Kashiwagi Atsunori 
Published: July 2006

OBJECTIVE—To examine the association of baseline measures in lower-leg arteries and conventional cardiovascular risk factors with the incidence of cardiovascular disease (CVD) events in type 2 diabetic patients with normal ankle-brachial indexes (ABIs) (&gt;0.9).
RESEARCH DESIGN AND METHODS—We studied 129 type 2 diabetic patients and 35 age-matched nondiabetic subjects with no apparent CVD consecutively admitted to our hospital. At baseline, total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery was evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Patients were followed 4.8 ± 1.5 years (range 3.0–8.2) or until their first event of CVD.
RESULTS—On follow-up, 16 patients developed primary CVD events. Patients with CVD had lower blood flow (P &lt; 0.01) and higher vascular resistance (P &lt; 0.05) than patients without CVD. When the patients were grouped into tertiles according to their levels of total flow volume (129.6–85.5, 85.3–63.3, and 62.7–23.8 ml/min), Kaplan-Meier analysis showed a higher probability of developing CVD events in patients in the lowest than in patients in the highest (P = 0.0199, log-rank test) tertile. Multivariate Cox proportional hazards analysis revealed that the lowest tertile for flow volume (hazard ratio [HR] 8.60, 95% CI 1.61–45.97, P = 0.012), hypertension (3.99, 1.12–14.25, P = 0.033), and smoking status (12.01, 1.21–119.28, P = 0.034) were significant independent predictors of CVD events.
CONCLUSIONS—We have demonstrated that low blood flow estimates in lower-leg arteries may be predictive for CVD events among Japanese patients with type 2 diabetes even though they have a normal ABI.
Impaired Exercise-Induced Blood Volume in Type 2 Diabetes With or Without Peripheral Arterial Disease Measured by Continuous-Wave Near-Infrared Spectroscopy
Authors: Mohler Emile R. , Lech Gwen , Supple Gregory E. , Wang Hao , Chance Britton 
Published: July 2006

OBJECTIVE—Diabetes is a significant risk factor for peripheral arterial disease (PAD) and is associated with accelerated atherosclerosis and limb loss. However, the pathophysiology involved in PAD is unclear. This study was conducted to evaluate the hemodynamic response to exercise of patients with and without diabetes and PAD.
RESEARCH DESIGN AND METHODS—The hemodynamic response in calf muscles of patients with diabetes, PAD, or both was determined using near-infrared spectroscopy (NIRS). Patients performed both a plantar-flexion and treadmill-walking exercise regimen.
RESULTS—Skeletal muscle capillary blood volume expansion during exercise, as measured by NIRS, was significantly impaired in the lower extremities of diabetic patients with a normal ankle-brachial index. The relative deoxygenation and oxygenation recovery times measured by NIRS correlates significantly with the presence of PAD.
CONCLUSIONS—Patients with diabetes have reduced capillary volume expansion even without PAD. This is likely due to impaired vasodilation secondary to endothelial dysfunction. Further studies are needed to determine whether pharmaceutical intervention improves the blood volume expansion in the diabetic state.
Frequency and Temporal Profile of Poststroke Hyperglycemia Using Continuous Glucose Monitoring
Authors: Allport Louise , Baird Tracy , Butcher Ken , MacGregor Lachlan , Prosser Jane , Colman Peter , Davis Stephen 
Published: July 2006

OBJECTIVE—Poststroke hyperglycemia (PSH) is common and has adverse effects on outcome. In this observational study, we aimed to describe the frequency and temporal profile of PSH using a continuous glucose monitoring system (CGMS) in patients with and without diabetes.
RESEARCH DESIGN AND METHODS—Fifty-nine patients with acute hemispheric ischemic stroke were prospectively studied with the CGMS, regardless of medication, admission plasma glucose value, and diabetes status. The CGMS records interstitial glucose every 5 min for 72 h.
RESULTS—On admission, 36% of patients had preexisting diabetes. At the earliest analyzed time point of 8 h from stroke onset, 50% of nondiabetic subjects and 100% of diabetic patients were hyperglycemic (≥7 mmol/l). This early-phase hyperglycemia was followed by a decrease in glucose 14–16 h poststroke when only 11% of nondiabetic and 27% of diabetic patients were hyperglycemic. A late hyperglycemic phase 48–88 h poststroke was observed in 27% of nondiabetic and 78% of diabetic patients. Thirty-four percent of nondiabetic and 86% of diabetic patients were hyperglycemic for at least a quarter of the monitoring period. Multivariate regression analysis demonstrated that diabetes, insular cortical ischemia, and increasing age independently predicted higher glucose values.
CONCLUSIONS—Poststroke hyperglycemia is common and prolonged despite treatment based on current guidelines. There are early and late hyperglycemic phases in nondiabetic as well as diabetic patients. Treatment protocols with frequent glucose measurement and intensive glucose-lowering therapy for a minimum of 72 h poststroke need to be evaluated.
Who Is Tested for Diabetic Kidney Disease and Who Initiates Treatment?
Authors: Johnson Susan L. , Tierney Edward F. , Onyemere Kingsley U. , Tseng Chien-Wen , Safford Monica M. , Karter Andrew J. , Ferrara Assiamira , Duru O. Kenrick , Brown Arleen F. , Narayan K.M. Venkat , Thompson Theodore J. , Herman William H. 
Published: July 2006

OBJECTIVE—We examined factors associated with screening for albuminuria and initiation of ACE inhibitor or angiotensin receptor blocker (ARB) treatment in diabetic patients.RESEARCH DESIGN AND METHODS—We conducted surveys and medical record reviews for 5,378 patients participating in a study of diabetes care in managed care at baseline (2000–2001) and follow-up (2002–2003). Factors associated with testing for albuminuria were examined in cross-sectional analysis at baseline. Factors associated with initiating ACE inhibitor/ARB therapy were determined prospectively.RESULTS—At baseline, 52% of patients not receiving ACE inhibitor/ARB therapy and without known diabetic kidney disease (DKD) were screened for albuminuria. Patients ≥65 years of age, those with higher HbA1c, those with cardiovascular disease (CVD), and those without hyperlipidemia were less likely to be screened. Of the patients with positive screening tests, 47% began ACE inhibitor/ARB therapy. Initiation of therapy was associated with positive screening test results, BMI ≥25 kg/m2, treatment with insulin or oral antidiabetic agents, peripheral neuropathy, systolic blood pressure ≥140 mmHg, and CVD. Of the patients receiving ACE inhibitor/ARB therapy or with known DKD, 63% were tested for albuminuria.CONCLUSIONS—Screening for albuminuria was inadequate, especially in older patients or those with competing medical concerns. The value of screening could be increased if more patients with positive screening tests initiated ACE inhibitor/ARB therapy. The efficiency of screening could be improved by limiting screening to diabetic patients not receiving ACE inhibitor/ARB therapy and without known DKD.
Deficiencies of Cardiovascular Risk Prediction Models for Type 1 Diabetes
Authors: Zgibor Janice C. , Piatt Gretchen A. , Ruppert Kristine , Orchard Trevor J. , Roberts Mark S. 
Published: July 2006

OBJECTIVE—Cardiovascular risk prediction models are available for the general population (Framingham) and for type 2 diabetes (U.K. Prospective Diabetes Study [UKPDS] Risk Engine) but may not be appropriate in type 1 diabetes, as risk factors including younger age at diabetes onset and presence of diabetes complications are not considered. Therefore, our objective was to examine the accuracy of Framingham and UKPDS models for predicting coronary heart disease (CHD) in a type 1 diabetic cohort.
RESEARCH DESIGN AND METHODS—Ten-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective cohort study of 658 subjects with childhood-onset type 1 diabetes diagnosed between 1950 and 1980 first seen in 1986–1988, were analyzed. EDC study data were used to calculate the 10-year probability of CHD (fatal CHD, nonfatal myocardial infarction, or Q-waves) applying to the Framingham and UKPDS equations.
RESULTS—Mean age at CHD onset was 39 years. When fatal/nonfatal myocardial infarction and CHD death were modeled, both the UKPDS and Framingham models showed significant lack of calibration (P &lt; 0.0001) but moderate discrimination (0.76 UKPDS, 0.77 Framingham men, and 0.88 Framingham women). Both the UKPDS and Framingham models underestimated probability of events in highest risk deciles.
CONCLUSIONS—Currently available CHD models poorly predict events in type 1 diabetes. Future research should focus on determining the risk factors accounting for the lack of fit and developing prediction models specific to this high-risk group.