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Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta  = 5.72 × 10 -4 ), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10 -16 ). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis.

Reelin (RELN) is identified as a risk gene for major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). However, the role of its downstream signaling molecule, the low-density lipoprotein receptor-related protein 8 (LRP8) in these illnesses is still unclear. To detect whether LRP8 is a susceptibility gene for SCZ and BPD, we analyzed the associations of single nucleotide polymorphisms (SNPs) in LRP8 in a total of 47,187 subjects (including 9379 SCZ patients; 6990 BPD patients; and 12,556 controls in a screening sample, and 1397 SCZ families, 3947 BPD patients, and 8387 controls in independent replications), and identified a non-synonymous SNP rs5174 in LRP8 significantly associated with SCZ and BPD as well as the combined psychosis phenotype (P meta  = 1.99 × 10 -5 , odds ratio (OR) = 1.066, 95 % confidence interval (CI) = 1.035-1.098). The risk SNP rs5174 was also associated with LRP8 messenger RNA (mRNA) expression in multiple brain tissues across independent samples (lowest P = 0.00005). Further exploratory analysis revealed that LRP8 was preferentially expressed in fetal brain tissues. Protein-protein interaction (PPI) analysis demonstrated that LRP8 significantly participated in a highly interconnected PPI network build by top risk genes for SCZ and BPD (P = 7.0 × 10 -4 ). Collectively, we confirmed that LRP8 is a risk gene for psychosis, and our results provide useful information toward a better understanding of genetic mechanism involving LRP8 underlying risk of complex psychiatric disorders.

Aims: Previous reports have provided conflicting data regarding the relationship between length of stay (LOS) and subsequent readmission risk among patients hospitalized for heart failure (HF)., Methods and Results: We performed a post-hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial to evaluate the differences in LOS overall and between geographic regions (North America, South America, Western Europe, and Eastern Europe) in association with all-cause and cause-specific [HF, cardiovascular (CV) non-HF, and non-CV] readmissions within 30 days of discharge after HF hospitalization. The present analysis included 4020 patients enrolled from 20 countries who were alive at discharge. Median [interquartile range (IQR)] LOS was 8 (4-11) days. The 30-day readmission rates were 15.7% [95% confidence interval (CI) 14.6-16.8] for all-cause; 5.6% (95% CI 4.9-6.3) for HF; 4.4% (95% CI 3.8-5.1) for CV non-HF; and 5.8% (95% CI 5.1-6.6) for non-CV readmissions. There was a positive correlation between LOS and all-cause readmissions (r = 0.09, 95% CI 0.06-0.12). The adjusted odds ratio for the top (≥14 days) vs. the bottom (≤3 days) quintile for LOS was 1.39 (95% CI 0. 92-2.11) for all-cause readmissions, 0.43 (95% CI 0.24-0.79) for HF, 2.99 (95% CI 1.49-6.02) for CV non-HF, and 1.72 (95% CI 1.05-2.81) for non-CV readmissions. With the exception of Western Europe, these findings remained largely consistent across geographic regions., Conclusion: In this large multinational cohort of hospitalized HF patients, longer LOS was associated with a higher risk for all-cause, CV non-HF, and non-CV readmissions, but a lower risk of HF readmissions within 30 days of discharge. These results may inform strategies to reduce readmissions., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Aims: This study sought to investigate regional variation in clinical characteristics, therapy utilization, and post-discharge outcomes among patients hospitalized for heart failure (HHF) enrolled in the multinational ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes) trial., Methods and Results: The ASTRONAUT trial randomized 1615 HHF patients with ejection fraction ≤40% to aliskiren or placebo. Enrolled patients were from Eastern Europe (n = 495, 30.7%), Asia/Pacific (n = 439, 27.2%), Western Europe (n = 395, 24.5%), Latin America (n = 163, 10.1%), and North America (n = 123, 7.6%). Marked differences were seen across geographic regions in terms of baseline demographics, vital signs, laboratory tests, co-morbidity burden, and use of guideline-recommended therapies. All-cause death at 12 months ranged from 7.3% in North America to 26.7% in Asia/Pacific, with differences largely driven by sudden cardiac death. Rates of repeat HHF at 12 months ranged from 22.7% in Latin America to 43.9% in North America. After adjustment for patient characteristics, region was an independent predictor of death at 12 months, with highest risk in Asia/Pacific (hazard ratio 3.04, 95% confidence interval 1.47-6.29, compared with North America) and lowest risk in North America and Western Europe. There was no association between region and the composite of cardiovascular mortality or HHF., Conclusion: For patients enrolled in this HHF trial, baseline characteristics and risk of death differed markedly by geographic region. Rates of death and repeat HHF demonstrated a general inverse relationship. Global differences in patient characteristics and outcomes should be accounted for when designing future HHF clinical trials., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)

Aims: In patients with chronic heart failure (CHF), left bundle branch block (LBBB) is associated with an increased risk of cardiovascular mortality. We aimed to investigate the association of LBBB with short- and long-term outcome in patients discharged after a de novo episode of acute heart failure (AHF) or AHF complicating a mild CHF., Methods and Results: Patients with no history of New York Heart Association class III and IV CHF, who were admitted for a severe AHF episode and enrolled in the prospective observational EFICA study (n = 403), were included. Left bundle branch block prevalence was 16%. Patients with LBBB had a higher prevalence of dilated cardiomyopathy (23 vs. 10%, P < 0.005), a higher percentage of AHF episodes without identified precipitating factor (15 vs. 2%, P < 0.001), and were less likely to present increased markers of cardiac injury (41 vs. 56%, P = 0.04). The 4-week mortality was 24.8% with no difference between LBBB and no LBBB patients. Left bundle branch block was however an independent predictor of 1-year mortality in the 4-week survivors [hazards ratio (95% confidence interval) = 2.01 (1.12-3.64), P = 0.02]., Conclusion: Long-term outcome of patients surviving a severe episode of de novo AHF or AHF complicating a mild CHF is worsened by LBBB. These patients may constitute a subgroup at high risk in whom specific therapeutic solutions should be investigated.

The extracellular cardiac matrix (ECCM) plays an important role in the support of myocytes and fibroblasts. ECCM turnover is influenced by ischemia, stretch, inflammation, and neurohormonal mediators. Myocardial fibrosis is the consequence of several pathologic processes mediated by mechanical, neurohormonal, and cytokine factors. It is a major determinant of diastolic dysfunction and pumping capacity and may result in tissue heterogeneity, dys-synchrony, and arrhythmias. The measurement of various serum peptides arising from the metabolism of collagen types 1 and 3, of degradation fragments, and of specific metalloproteinases may provide noninvasive assessment of fibrosis. ECCM biomarkers are clinically useful tools, particularly given the potential for cardioprotective and cardioreparative pharmacologic strategies.

Background: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction., Methods and Results: In a substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months., Conclusions: Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post-acute myocardial infarction collagen turnover changes.

Severe hypertension is a major cardiovascular and cerebrovascular risk factor and places the patient in the category of high cardiovascular risk, independently of any other cardiovascular risk factors. The economic burden of hypertension is high, with severe hypertension the 4th most costly disease (5.5 billion Euros) on the French list of chronic diseases ("Affections de longue durée" or ALD) for which the national health insurance funds reimburse 100% of expenses. The French High Health Authority recently suggested removing hypertension from the ALD list. This recommendation, however, had no scientific rationale but was motivated instead by economic and political factors and may endanger the quality of management of hypertensive patients. The previous ALD criteria for severe hypertension require revision to bring them into line with the recommendations of professional and learned societies. The ALD list should include severe hypertension as well as complicated and treatment-resistant hypertension, with the diagnosis documented by ambulatory or self blood pressure monitoring.

Background and Aims: The multiplicity of vaccine injections during childhood leads to iterative painful and stressful experiences which may lead in turn to anticipated pain and then possibly to a true needle phobia. We aimed at evaluating a multifactorial strategy of pain management combining pharmacological and non-pharmacological approaches during vaccination, as compared to usual care, in 4- to 12-year-old children., Methods: In all, 239 children were enrolled by 25 family practitioners in an open-label study. After a pseudo-randomization, usual pain management (n = 132) was compared to a multifactorial strategy (n = 107) associating preliminary application of an anesthesic patch, preferential use of specified vaccines, child education by the parents and the doctor, parental accompaniment and child distraction with soap bubbles during the procedure. The primary outcome (i.e. child pain) was assessed with a self-report scale named visual analog scale (VAS) of pain., Results: A significant decrease in pain was obtained using the multifactorial strategy, as assessed by self-reported VAS (P < 0.0001). This was confirmed by another self-report scale (the facial pain scale revised: P = 0.005), as well as with hetero-evaluations by GPs and parents [Children's Hospital of Eastern Ontario Pain Scale: P = 0.0007; GPs VAS (P < 0.0001), parents VAS (P < 0.0001)], which were secondary outcome criteria., Conclusions: This multifactorial method significantly decreases vaccination pain in 4- to 12-year-old children. This strategy could make vaccines more acceptable to children and may improve child-doctor relationships and contribute to a decrease in child fear about health care.

Peripheral vascular disease is one component of the diabetic foot. Diabetic patients should be assessed for lower limb arterial disease resulting from the high prevalence of this complication. Medical management includes the treatment of vascular risk factors, anti-thrombotic agents, and walking rehabilitation. Vascular testing is required in the presence of a foot wound. Ischemia alone is implicated in only 10% of foot wounds, whereas inadequate tissue perfusion is often a nonhealing factor. Managing a diabetic patient with a foot wound will be more effective in a dedicated center providing vascular assessment, a multidisciplinary pre concerted plan, and vascular management. Lowering the number of major amputations in the diabetic population requires better arterial evaluation and treatment (vascular functional testing and revascularization when possible).

Perindopril, a prodrug ester of perindoprilat, is an angiotensin-converting enzyme inhibitor that lowers angiotensin II and potentiates bradykinin. This agent has proven efficacy in a wide range of cardiovascular diseases. Its efficacy, safety and tolerability are well established in the treatment of hypertension. Beyond pharmacodynamic effects shown in lowering blood pressure, perindopril was also involved in the improvement of endothelial function and the normalization of vascular and cardiac structure and function. Large morbidity-mortality trials, such as the European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS) and Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), have shown that treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases (including stable coronary disease), whether or not they are hypertensive.

Haemorheological changes have been described in hypertension as well as in diabetes mellitus. Antihypertensive treatment improves rheology in hypertensive patients. The aim of this study was to describe the haemorheological profile and its impact on shear stress in hypertensive type 2 diabetes mellitus patients (HT + DM) and to investigate the effect of antihypertensive therapy on blood rheology using a double-blind randomized protocol, comparing the calcium antagonist amlodipine with the angiotensin-converting enzyme (ACE) inhibitor enalapril. A total of 144 patients with hypertension and type 2 diabetes (64 of transversal study and 80 of randomized clinical trial) were compared with 92 controls belonging to a transversal study. Secondarily, in a separate analysis, therapeutic effects of calcium antagonist amlodipine and ACE inhibitor enalapril were compared in a longitudinal, randomized trial in the patients. We assessed whole-blood viscosity, plasma viscosity, partial and total disaggregation times, haematocrit and fibrinogen. Radial artery systolic flow velocity was measured by pulsed Doppler. Shear stress was calculated as the product of flow velocity x whole-blood viscosity. Compared with controls, patients had significantly higher whole-blood viscosity for all shear rates (P < 0.001) as well as higher arterial diameter and systolic blood flow velocity (2.8 +/- 0.3 vs. 2.6 +/- 0.3 mm, P < 0.001; and 50.8 +/- 11.6 vs. 45.6 +/- 9.8 cm/s, P = 0.01, respectively). Whole-blood viscosity at shear rate gamma = 128/s tended to increase with amlodipine (+1.13%) and decrease with enalapril (-2.47%) (P = 0.028 for inter-group difference). In hypertensive diabetic patients, hyperviscosity contributes to increased shear stress. Haemorheological disturbances in these patients are not significantly influenced by blood pressure lowering with antihypertensive therapy by ACE inhibitor enalapril or calcium antagonist amlodipine. Other factors potentially contributing to rheology and arterial changes may be more critical in HT + DM patients and need further investigation.

Unlabelled: Paediatric fever is a frequent reason of consulting a paediatrician or a general practitioner (30% of paediatric consultations)., Aim of the Study: This investigation aimed at reporting the knowledge level concerning child's and infant's fever in a urban population and the resulting practices. Two thousand and six hundred questionnaires were distributed in June 2004 in the 29 scholar institutions of Metz agglomeration (France) classified in 3 categories according to socio-economical conditions of parents: 3 institutions of city centre (high socioeconomical conditions), 18 sub-urban institutions (intermediary conditions) and 8 institutions located in priority education zones (ZEP) (defavorable conditions)., Results: One thousand and thirty-eight questionnaires could be analyzed (40%): 176 in city centre, 634 in sub-urban zones and 228 in ZEP. Fever threshold at 38 degrees C is well-known and fever measuring methods used are mostly in accordance with the recommendations. The best room temperature was known and the use of antipyretic physical means underlined only a few cases of obvious mistakes. All parents were informed about worrying signs related with fever even if doctor's resort was excessive. Acetaminophen was the reference molecule before ibuprofen whereas the use of aspirin was decreasing. Antipyretic treatments methods used by parents were often unsuitable, leading to therapeutical inefficacy, overdosage or noxious drug interactions, mainly because of a lack of knowledge about drug components., Conclusion: This investigation underlines insufficient knowledge and noxious management practices among parents with unfavourable socio-economical conditions which lead us to recommend targeted information preferentially in areas gathering together most unfavourable socio-economical condition populations.

The aim of the present work was to review published studies investigating the dose-related efficacy on blood pressure (BP) of olmesartan and of other commercially available angiotensin II type I receptor blockers (ARBs). Patient population comprises mild to moderate hypertensive adult patients. We selected studies with comparable design and dose ranges. Dose-effect relationship plots were fitted for diastolic (DBP) and systolic (SBP) BP to the simplified E(max) model. We also examined controlled studies of olmesartan vs. other individual ARBs. Our overview was based on 7280 patients, of which 5769 received an ARB and 1511 received placebo. Except for losartan, the data fitted correctly to the E(max) model, with correlation coefficients ranging from 0.77 to 0.99. BP-lowering efficacy defined as E(max) was superior with olmesartan, (DBP/SBP mmHg: -9.0/-12.4) when compared with candesartan (-6.7/-11.3), irbesartan (-6.5/-11.2) and valsartan (-6.3/-8.9). Head-to-head comparisons of olmesartan to each of the other ARBs used at per-label 'recommended doses', support the finding of a greater BP-lowering effect of olmesartan. This overview suggests that clinically relevant differences in maximal efficacy, as well as in efficacy of per-label recommended doses can be evidenced among individual ARBs. Olmesartan efficacy was consistently at the highest end of the range of efficacy of ARBs studied.

Amputations through the distal interphalangeal joint or distal to this joint are frequent and they represent probably one of the best indications for replantation. Details on the vascular anatomy of the fingertip have to be perfectly known by the surgeon who will have to deal with these replantations. Factors such as age, mechanism of amputation and type of anastomosis will influence the overall success rate of the procedure. Return of a true static two points discrimination can be observed in children even in the absence of any neural repair.

The prevalence of conduction disturbances, particularly left bundle branch block (LBBB), is strongly correlated with age and with the presence of cardiovascular disease. LBBB has been reported to affect approximately 25% of the heart failure (HF) population and it is likely that the deleterious role of such conduction disorders in the progression to HF has been underestimated. The purpose of this article is to review the data from the literature indicating that LBBB may have a causative role, mediated through the resulting intra-ventricular asynchrony, in the deterioration of cardiac function and the development of cardiac remodelling and HF. It also aims to address the potential for future clinical therapies for this conduction disorder.

Incidence and prevalence of Type 2 Diabetes, together with its long term complications is explosively rising. The trans-border project "INTERREG III" tries to explore the epidemiology in the 3 concerned countries and to tie a network between the health providers. Estimation of prevalence is around 3% of the adult population but rising for example in the Grand Duchy by 4.5% per year, meaning the number of affected patients will double in 16 years, mainly due to the increase in obesity. Chronic renal insufficiency will rise and the number of patients will double in 8 years. Cardiovascular diseases and peripheral necrosis explain the high rate of hospitalisations and the loss of Life-expectancy that seems to be reduced by 5 to 10 years. A cost analysis in this article reveals the necessity of primary and secondary prevention programs of "diabesity" in this region, together with better multidisciplinary approaches of treatment and follow-up. This article emphasizes the need of a collaboration of all actors in the field, medical and para-medical.

Acute heart failure syndromes (AHFS) is a broad spectrum of heterogeneous conditions including pulmonary oedema, hypertensive crisis, worsening exacerbated CHF and cardiogenic shock. HF hospitalizations have steadily risen with more than one million in 2004 in the United States and a similar number has been reported in Europe. Each year heart failure accounts for 6.5 million days spent in hospital in the USA and 1.4 million days in France. Mortality data are derived from registries or clinical trials. Registry data in patients admitted to general or cardiology wards such as in Euroheart Failure Survey and ADHERE provide a far more optimistic picture compared with data from consecutive unselected patients in the most acute situation. such as in EFICA. Four-week mortality was higher than 25% in this case. A great pathophysiologic understanding of the different features of the various AHFS is needed in order to identify targets for therapy and research. This includes hemodynamics, the role of myocardial injury, neurohormonal and cytokine abnormalities and the cardiorenal syndromes. So far, very little progress has been made in developing new, effective therapies and implementing management guidelines in this patient population. Future clinical trial endpoints should be better designed and tailored to the various pathophysiological conditions of this complex syndrome. The goal of AHFS therapy is not only to prevent disease progression but also to have a beneficial effect on an acute event that exacerbates disease progression. A combined endpoint assessing survival and rehospitalisation rates is becoming increasingly popular for acute therapies. Specific trials may also need to be designed according to the time of access to the patient.

Heart failure continues to significantly impact morbidity and mortality after acute myocardial infarction (AMI), especially when associated with left ventricular systolic dysfunction (LVSD). Therefore, routine use of optimal therapy for patients with heart failure after AMI is needed in the future. Data from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) has demonstrated that addition of eplerenone to standard therapy in patients with LVSD and clinical heart failure post-AMI significantly improves outcomes in these patients, providing the basis for acceptance of aldosterone blockade as an integral component of therapy. However, further studies are needed to more broadly explore the usefulness of aldosterone blockade in heart failure therapy. As research clarifies the many complex pathophysiologic processes involved in post-AMI remodeling, treatment should continue to move beyond symptom-targeted therapies to disease- and mechanism-targeted therapies that will further improve outcomes in the setting of heart failure post-AMI and beyond.

Objectives: The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m(2)), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease., Background: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy., Methods and Results: We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r=0.24; P=0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r=0.27; P=0.004), indexes of insulin resistance (HOMA (r=0.27; P=0.003), insulin (r=0.24; P=0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r=-0.27; P=0.004) and fat trunk/fat leg ratio (r=0.24; P=0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r (2)=0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r (2)=0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r=0.39; P=0.0002), followed by systolic blood pressure (r=0.19; P=0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r=-0.27; P=0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects., Conclusion: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.

Background: Few data are available on the quality of the protocols promoted by the University Hospital Centers (CHU) in France, and there is no standardised method for evaluating protocol quality. The Clinical Research Centre (CIC) of Nancy developed a checklist-based tool aimed at evaluating the quality of institutional protocols., Objective: The objective of this study was to evaluate the performance of this tool for assessing the quality of the protocols promoted by the CHU., Methods: A prospective parallel-group study design, controlled with cluster randomisation, was used. The checklist was applied within the Directions of Clinical Research (DRC) for 4 months. Sixty four protocols were analysed., Results: Before intervention there was no significant difference in quality scores between the two groups. Compared with baseline, there was a significant improvement of the methodological and regulation median score (81.7 +/- 13.7 vs 90.4 +/- 9.2) only in the intervention group (p = 0.040). Changes in the two groups over time were not significantly different from each other using analysis of variance (p = 0.501)., Conclusion: In an observation limited to 12 CHU in France, the quality of the promoted protocols was judged as suboptimal and able to be improved. Initiation of quality assurance tools, such as the one used in this study, was associated with some spontaneous improvement, but did not improve the result significantly.

Context: Clinical research regulations currently undergo major revisions mainly initiated by the European harmonization. Regulations must indeed all be adapted to the contents of directive 2001/20/CE applicable in France on 1 May 2004. One of the four principal modifications of the Huriet-Sérusclat law dating from 4 March 2002 relates to the transmission of the main results of research protocols to participating patients. However, no precise directives or information are provided to investigators and sponsors on how to implement this., Objective: Our objective was to create a tool to assist investigators providing patients with the main results of clinical research studies., Materials and Methods: We first consulted the various participants in biomedical research: ethics committee (CCPPRB), Clinical Investigation Centres (CIC), institutional sponsors, participating patients, plus research protocols and lawyers specialized in forensic medicine., Conclusion: After analysis of their answers, we worked out the bases of our tool. This tool is tested in an implementation phase.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

Background: Patients with chronic pancreatitis (CP) are at high risk of antioxidant deficiencies. Furthermore, this disease can lead to diabetes mellitus (DM) that could exacerbate the severity of oxidative stress. Oxidative stress and the resulting LDL oxidation are a major cause of atherosclerosis., Objective: The objective of the study was to ascertain whether diabetes significantly modifies oxidative status in patients with CP., Design: CP patients with or without DM were compared with type 1 DM patients and healthy control subjects., Results: Two-way factorial analyses showed that a decrease in the plasma concentrations of vitamin A, vitamin E, and carotenoids accompanied both CP and DM, and CP was also associated with lower plasma concentrations of selenium and zinc, lower catalase activity, and higher plasma concentrations of copper. The lag phase of LDL oxidation was lower in CP patients with or without DM than in the control subjects, whereas there was no significant difference between type 1 DM patients and control subjects. Multivariate analysis showed that LDL vitamin E (R2 = 0.24, P < 0.0001) and fasting plasma glucose (R2 = 0.32, P < 0.0001) concentrations were the main determinants of the lag phase of LDL oxidation., Conclusions: Antioxidant status is altered in CP patients, particularly in those who also have DM. In these patients, a vitamin E deficiency and an elevated plasma glucose concentration were associated with significantly higher LDL oxidizability.

The thiazolidinediones (or glitazones) were recently added to the oral treatments for type 2 diabetes. Several recent studies, either in in vitro models or in animal models, lead to a better understanding of their mechanism of action. Recent, long term, controlled clinical studies, permit to define better their place and their condition of use (including adverse event prevention), as a monotherapy, or in association with metformin or a sulfonylurea when these drugs failed to achieve an optimal glycemic control. The beneficial metabolic effects of glitazones, generate great hopes for the prevention of the progressive beta-pancreatic cell function decline observed in type 2 diabetics, and possibly to prevent and/or to delay type 2 diabetes in high at-risk subjects. This review describe and discuss the most recent studies and their results.

We hypothesized that onset of sensory block is delayed in infected versus healthy tissues within the same nerve distribution after axillary brachial plexus block (ABPB) and that clonidine added to mepivacaine would enhance anesthesia and postoperative analgesia. Forty-one outpatients undergoing thumb/index paronychia surgery under ABPB were randomly assigned to receive in a double-blind fashion 400 mg mepivacaine plus either 100 microg clonidine (clonidine group, n = 21) or 2 mL saline (placebo group, n = 20). Onset of sensory block in the infected area was delayed compared with healthy areas of the same nerve distribution (24.7 +/- 5.5 min versus 21.3 +/- 7.2; P = 0.02 for median and 21.6 +/- 7.8 min; P = 0.04 for radial) within the placebo group. In the clonidine group, when compared to placebo i) onset of sensory block in both the median and radial nerve territories was accelerated (11.1 +/- 5.6 and 10.5 +/- 5.2 versus 21.3 +/- 7.2 and 21.6 +/- 7.8 min, respectively; P < 0.001), ii) onset of sensory block in the region of infection was accelerated (9.1 +/- 1.9 versus 24.7 +/- 5.5 min; P < 0.001), iii) duration of anesthesia (275 +/- 75 versus 163 +/- 57; P = 0.04) and time to first analgesic requirement (279 +/- 87 versus 197 +/- 84 min; P = 0.002) were prolonged with decreased visual analog scale scores at this time (30 +/- 18 versus 70 +/- 24; P < 0.001), and iv) verbal numeric rating scores were decreased at 24 h (1.7 +/- 2.2 versus 4.1 +/- 3.0; P = 0.002) and 48 h (0.1 +/- 0.5 versus 1.5 +/- 2.4; P = 0.01) postoperatively. Our findings suggest that in the setting of distal infected tissue surgery under ABPB infected tissues are resistant to anesthesia compared with healthy areas within the same nerve distribution and clonidine added to mepivacaine enhances both anesthesia and postoperative analgesia.

Aim: To evaluate the efficacy and safety of gliclazide modified release (MR), alone or combined with other oral antidiabetic drug(s) over 2 years in type 2 diabetic patients., Methods: Two consecutive periods: (i) a 10-month, double-blind comparative study, where 800 type 2 diabetic patients were randomized either to gliclazide MR (30-120 mg) once daily or to gliclazide (80-320 mg) twice daily. All the patients were then treated with gliclazide MR for a 2-month switch period; (ii) 549 patients were subsequently enrolled in a 12-month, open-label period on gliclazide MR alone or in combination according to glycaemic control, 507 of whom completed the study., Results: Glycated haemoglobin (HbA1c) significantly decreased from baseline over 2 years by -0.46 +/- 1.08% in the whole cohort of 2-year completed patients, -0.95% in the subgroup of diet-failed patients and by -0.34% in the subgroup of patients pretreated with one oral antidiabetic drug. HbA1c was reduced by -0.43 +/- 1.02% and by -0.51 +/- 1.16%, when gliclazide MR was used in monotherapy and in combination therapy, respectively. The overall incidence of symptoms suggestive of hypoglycaemia was 4.8 episodes/100 patient-year, with no severe episode. This incidence was similarly low in elderly patients and patients with impaired renal function., Conclusion: Gliclazide MR alone or in combination with another oral antidiabetic drug significantly improved glycaemic control in type 2 diabetic patients over 2 years with a very good safety profile, notably in the elderly and in patients with impaired renal function.

Toe joint transplantation is a valuable procedure for reconstruction of the PIP joint of the finger. The authors describe recent refinements in the surgical procedure that have permitted them to reduce the morbidity on the donor site and simplify the whole procedure. A single dorsal approach is used at a digital level, allowing exposure of the recipient vessels (palmar collateral artery and superficial dorsal vein) and resection of the joint remnants. The PIP transfer is harvested through a limited dorsal incision, and reconstruction of the donor toe is achieved using a bone graft and a cross-toe flap. An average range of motion of 43 degrees has been achieved in this series with a mean follow-up of 42 months.

Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 < or = DBP < or =110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5-10 mg or valsartan 40-80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: -17.8 +/- 10.9 vs. -14.6 +/- 11.2, P = 0.025, DBP: -12.7 +/- 7.2 vs. -10.9 +/- 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: -13.0 +/- 13.7/-10.8 +/- 9.1 vs. -7.2 +/- 19.4/-4.9 +/- 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4-9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.

Unlabelled: Adjuncts to local anesthetics for peripheral plexus blockade may enhance the quality and duration of anesthesia and postoperative analgesia. The analgesic, tramadol, has a unique mechanism of action that suggests efficacy as such an adjunct. It displays a central analgesic and peripheral local anesthetic effect. We designed a prospective, randomized, controlled and double-blind clinical trial to assess the effect of tramadol added to brachial plexus anesthesia. One-hundred patients scheduled for carpal tunnel release surgery under brachial plexus anesthesia were randomized into four groups. All patients received 1.5% mepivacaine 40 mL plus a study solution containing either isotonic sodium chloride (Group P, n = 17), tramadol 40 mg (Group T(40), n = 22), tramadol 100 mg (Group T(100), n = 20) or tramadol 200 mg (Group T(200), n = 20). We evaluated the time of onset of anesthesia, duration of sensory and motor blockade, duration and quality of postoperative analgesia, and occurrence of adverse effects. Onset and duration of sensory and motor blocks were not different among groups. The number of patients requesting analgesia in the postoperative period was significantly less in the 3 tramadol groups compared with the placebo group (P = 0.02); this was also noted with the placebo and T(40) groups compared with the T(200) group. No statistical significance was demonstrated between the placebo and the T(40) group or the T(100) group and the T(200) group. Furthermore, there was a significant trend effect among groups applying the Cochran-Armitage tendency test (P = 0.003), suggesting a dose-dependent decrease for additional postoperative analgesia requirements when tramadol was added. Side effects did not differ among groups, although they were more frequently recorded in the T groups. Our study suggests that tramadol added to 1.5% mepivacaine for brachial plexus block enhances in a dose-dependent manner the duration of analgesia with acceptable side effects. However, the safety of tramadol has to be investigated before allowing its use in clinical practice., Implications: Tramadol's unique mechanism of action suggests efficacy as a local anesthetic adjunct for peripheral plexus blockade. Our study demonstrates that tramadol, added to mepivacaine for brachial plexus anesthesia, extends the duration and improves the quality of postoperative analgesia in a dose dependent fashion with acceptable side effects.

Macrodactyly involving the great toe is difficult to treat when both the functional and cosmetic problems are addressed simultaneously. Partial resection of the distal phalanx is an easy way to reduce the length of the involved toe. However, there are cosmetic concerns with loss of the toenail. The authors report on a clinical case in which shortening and debulking of the toe was performed while preserving the hallux nail. The nail complex was transferred as an island flap to the dorsal aspect of the proximal phalanx. At the 1-year follow-up, the length of the reconstructed toe was significantly decreased, with a normal-looking nail.

Continuous glucose monitoring is a recent technique which appears to be highly useful in diabetic patients, particularly in children and adolescents. Its potential interest to study unstable diabetes, to detect asymptomatic and nocturnal hypoglycaemias, to adapt and/or to adjust insulin treatment, etc. has lead to several recent clinical studies, conducted in various conditions. The different techniques, the studies conducted in children and adult diabetic patients, as well as the main current indications for continuous glucose monitoring are described in this article.

Objective: Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic of current interest (imbalance between increased health-care costs and improvement in compliance with treatment and diet). An open label randomized prospective study was designed to compare changes in metabolic control over 6 months in patients managed with usual recommendations alone (conventional assessment group) or combined with SMBG., Research Design and Methods: Patients not treated with insulin or previously self monitored, 40 to 75 years of age, with a diagnosis of type 2 diabetes > 1 year and standardized HbA(1c) level > =7.5 and< =11% were randomized to either a control group or SMBG group. They were followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given the same device (Ascensia Esprit Discmeter, Bayer) and were required to perform at least 6 capillary assays a week (3 different days of the week, including weekend). Management of patients was standardized, including drugs, diet and physical activity. The primary efficacy criterion was change in HbA(1c) level in Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6 months using the calibrated DCA 2000(R) device (Bayer)., Results: Two hundred sixty five general practitioners randomized 988 patients (ITT Population), but 689 patients were evaluable for the primary criterion. At the endpoint, HbA(1c) was lower in the SMBG group (8.1 +/- 1.6%) than in the conventional treatment group (8.4 +/- 1.4%, P=0.012). The change in HbA(1c) levels between baseline and endpoint was classified into two classes: improvement if a change > 0.5% occurred, stability or worsening in case of a change< =0.5%; 57.1% of patients in the SMBG group vs 46.8% in the control group had an improvement in HbA(1c) level (P=0.007) after 3 months. A steady state was reached during the last 3 months. A multivariate logistic regression analysis was performed and identified factors predictive of improvement in HbA(1c) levels: HbA(1c) at baseline: odd ratio (OR)=1.749 (P<0.001), SMBG group (reference value: SMBG group): OR=0.665 (P=0.015), duration of diabetes: OR=0.953 (P=0.001) and BMI: OR=0.962 (P=0.039)., Conclusions: This study is the first multicenter, controlled, prospective trial conducted on a large number of patients demonstrating that SMBG was statistically associated with a better quality of metabolic control than usual traditional recommendations alone in type 2 diabetes.

An opinion poll was carried out during the ALFEDIAM Congress Bordeaux 2003. One hundred and thirty-seven participants (mean age 43.6 +/- 8.3 years/sex Ratio approximately 1) among whom 22.6% run private practices, 51.8% work in hospitals and 21.3% are both private and hospital practitioners, have been questioned about their conception of the prevention of type 2 diabetes. Prediabetes is an acknowledged entity for 61% of the people surveyed. Two thirds use as a diagnostical criterion, moderate fasting hyperglycemia and/or a impaired glucose tolerance. Oral glucose tolerance test (OGTT) is still commonly practised among 51.9% but that is done sparingly only to confirm the diagnosis of diabetes in presence either of several risk factors or of a moderate fasting hyperglycemia. According to 70% of the answers, the detection of diabetes must be repeated every year among at risk subjects aged over 45. The metabolic syndrome is defined according to diverse criteria. The right definition of ATP III is given only in 5% of the cases. As regards the treatment, the combined requirements of physical activity and dietary rules are approved by 97% of the answers. The majority of the persons questioned in the survey consider that a slight loss of weight (less than 5% of the initial weight) is sufficient in a high risk risk individual.On the other hand, opinions are divided as regards the use of drugs at the pre-diabetes stage. Metformin is the only one that is accepted by more than 50% with a rate of 58.4% of positive answers, acarbose and orlistat rating respectively 37.2% and 35%. However a great majority (83.6%) are in favour of the reimbursement of antidiabetic drugs in this indication, for high risk individuals, provided a study has clearly demonstrated the efficiency of the molecule concerned.

Data are reported for a series of 20 patients who were treated with the pins and rubbers traction system for fractures of the proximal interphalangeal joints of the long fingers. This technique allows fracture reduction with external dynamic traction and immediate active mobilization. Two patients in the series were lost to follow-up monitoring. For two others, the pins and rubbers traction system needed to be removed early (during the first week) because of intolerance or infection. Sixteen patients who were reexamined after minimal follow-up periods of 1 year demonstrated a mean active range of motion of 85.9 degrees for the injured joint; only one patient experienced intermittent pain.

Objective: To assess and compare the technical accuracy of portable glucose meters during the last decade., Research Design and Methods: One-thousand preprandial (pre) and postprandial (post) capillary whole-blood glucose values measured with meters owned mainly by diabetic patients were compared with a single laboratory method yearly from 1989 to 1999. A total of 21,950 capillary measurements and their corresponding laboratory reference values were analyzed at our clinic., Results: The lowest mean absolute difference was found in 1989 (pre: 2 +/- 22 mg/dl, post: 9 +/- 31 mg/dl) (mean +/- SD). The highest mean absolute difference was observed in 1993 (pre: 31 +/- 33 mg/dl) and 1996 (post: 50 +/- 35 mg/dl). The highest mean relative deviation was observed in 1990 (pre: 16.4%) and 1996 (post: 20.6%). The highest percentage of readings that were within a 5% deviation limit were observed in 1998 (pre: 44.5%) and in 1997 (post: 36.7%). Based on blood glucose levels within +/-5 and +/-10% of laboratory values, the technical accuracy of meters was similar for 1989 and 1999 (P = 0.27 and 0.52, respectively). The percentage of pre values in zone A of Clarke's error grid analysis was >90% in 1989, 1997, 1998, and 1999., Conclusions: The analytical performance of glucose meters decreased between 1990 and 1996 but was restored between 1997 and 1999. Nevertheless, our data suggest that the technical accuracy of glucose meters has not significantly improved during the last decade. Complementary studies taking into account the preanalytical improvements of the recent meters, as well as their calibration method, appear necessary.

Objective: This study was designed to test the accuracy of capillary ketonemia for diagnosis of ketosis after interruption of insulin infusion., Research Design and Methods: A total of 18 patients with type 1 diabetes treated by external pump were studied during pump stop for 5 h. Plasma and capillary ketonemia and ketonuria were determined every hour from 7:00 A.M. (time 0 min = T0) to 12:00 P.M. (time 300 min = T300). Plasma beta-hydroxybutyrate (beta-OHB) levels were measured by an enzymatic end point spectrophotometric method, and capillary beta-OHB levels were measured by an electrochemical method (MediSense Optium meter). Ketonuria was measured by a semiquantitative test (Ketodiastix). Positive ketosis was defined by a value of >/=0.5 mmol/l for ketonemia and >/=4 mmol/l (moderate) for ketonuria., Results: After stopping the pump, concentrations of beta-OHB in both plasma and capillary blood increased significantly at time 60 min (T60) compared with T0 (P < 0.001), reaching maximum levels at T300 (1.30 +/- 0.49 and 1.23 +/- 0.78 mmol/l, respectively). Plasma and capillary beta-OHB values were highly correlated (r = 0.94, P < 0.0001). For diagnosis of ketosis, capillary ketonemia has a higher sensitivity and negative predictive value (80.4 and 82.5%, respectively) than ketonuria (63 and 71.8%, respectively). For plasma glucose levels >/=250 mg/dl, plasma and capillary ketonemia were found to be more frequently positive (85 and 78%, respectively) than ketonuria (59%) (P = 0.017). The time delay to diagnosis of ketosis was significantly higher for ketonuria than for plasma ketonemia (212 +/- 67 vs. 140 +/- 54 min, P = 0.0023), whereas no difference was noted between plasma and capillary ketonemia., Conclusions: The frequency of screening for ketosis and the efficiency of detection of ketosis definitely may be improved by the use of capillary blood ketone determination in clinical practice.

The glycemic variations observed in nondiabetic subjects are primarily related to the post-prandial metabolic responses generated by the food intake. This physiological glycemic variability is reproducible between two successive days under conditions of similar meals and activities. In insulin-treated diabetic patients, glycemic instability is directly related to loss of glucose homeostasis due to the failure then the deficiency of endogenous insulin secretion, but its physiopathological implication in term of diabetic angiopathy risk remains to be determined. Other exogenous glycemic instability factors are known and have to be corrected (not adapted repartition of the meals and/or the insulin doses during the day, inappropriate choices in insulin regimens, errors in insulin adjustments, inadequate insulin injection). Classical glycemic measurements used to appreciate the quality of the glycemic control do not provide or give partial and erroneous information on quality of glycemic stability. It's particularly the case for glycated hemoglobin and glycemic average. In order to exactly quantify glycemic variability, specific tools of measurement or calculation can evaluate the intra-day glycemic variations or excursions (MAGE), the day-to-day glycemic variations or excursions (MODD), the meal-related glycemic excursions (MIME) or the risk of severe hypoglycemia (LBGI). Some of these tools are easy to use, other much complex or difficult to apply in clinical practice, even by using new methods such as the continuous glucose monitoring system (CGMS). Thus, asymptomatic glycemic variability is related to loss of glucose homeostasis, but also to irrelevant or incompatibility of the treatments used to obtain glucose control in insulin-treated diabetic patients. The evaluation of glucose instability can be provided using new methods of glucose monitoring and could be useful to optimize the therapeutic regimens in some of these diabetic patients.

Objective: Performance criteria have been established for in vitro blood glucose monitoring, particularly for the self-monitoring of blood glucose using glucose meters. Devices intended for use in the future, such as the continuous glucose monitoring system (CGMS), should satisfy similar criteria, particularly in diabetic patients under intensive therapy., Research Design and Methods: The analysis was conducted on 18 type 1 diabetic patients (not controlled, HbA(1c) >7.5%) treated by external pump using insulin analogs. Each patient received a glucose sensor for 3 days during his/her hospitalization and was instructed in its operation. Medtronic criteria were used to determine the accuracy of the CGMS. In addition, the data were analyzed according to American Diabetes Association (ADA) criteria, Clarke Error Grid analysis, and method of residuals, with the glucose oxidase method using a Beckman analyzer used as the reference method. Specificity and sensitivity were evaluated from the viewpoint of accuracy in the detection of hypoglycemia. For nine patients, two glucose sensors were simultaneously inserted into an abdominal site to determine the reproducibility of the system. RESULTS-Among the 33 glucose sensors inserted, 6 (18%) were nonfunctional. The mean duration of CGMS recording was 63 +/- 12 h. From all of the 692 sets of data that paired glucose readings and CGMS, the coefficients of correlation ranged from 0.87 to 0.92 and the mean absolute error ranged from 12.8 to 15.7%. The time experienced in hypoglycemia (<55 mg/dl) was reported at 86 +/- 62 min/day. Only 39% of the CGMS values satisfied the ADA precision criteria to within +/-10%, and 19% of these values satisfied the future ADA precision criteria of accuracy to within +/-5%. The means of difference method showed that the CGMS slightly underestimated the plasma glucose values (mean = -12 mg/dl). Error grid analysis showed only 77% of the glucose sensor values were in zone A, and 98.9% were in zones A and B. Two values fell in zone C and a single value fell in zone D. The sensitivity and specificity of the CGMS to detect hypoglycemia were 33 and 96%, respectively. A total of 6666 paired sensor values were recorded with a coefficient of correlation of 0.84 with a coefficient of variation of 8.25%., Conclusions: CGMS could be useful in routine clinical practice to provide much more information on the glucose profile than intermittent self-monitoring of blood glucose (SMBG). However, CGMS cannot be used as a replacement for glucose meters because it does not satisfy the conventional performance goals set down for in vitro glucose measurements and could therefore lead to clinically incorrect treatment decisions.

In an exclusively pediatric population, this retrospective study examined the functional and aesthetic results after distal replantation without nerve suture. The aim was to demonstrate, in the child, the presence of spontaneous nervous regeneration resulting in a fingertip pulp with discriminatory sensation. Eight amputations in eight children with a mean age of 9 years and 2 months on the day of the accident were reviewed. The cases were managed by a single surgeon over a period of 8 years and were collected from two different hand centers. The patients were then examined by a different surgeon, and the data were collected. Sensibility was evaluated using the Weber, Semmes-Weinstein, and wrinkle tests. The results were excellent, with mean values of 4.6 mm for the Weber test, 3.3 for the Semmes-Weinstein test, and a positive wrinkle test in all subjects. All patients thus recovered discriminatory sensation with minimal aesthetic sequelae. The usual factors adversely affecting the results of the replantation (ischemic time, level and mechanism of the amputation, and quality of the venous return) were examined, but no statistical analysis was performed because of the small sample size. This study demonstrates the presence of the clinical phenomenon of adjacent neurotization in the absence of nerve repair. It thus confirms that children are excellent candidates for replantation of the distal extremities, even when nerve suture is not performed.

Objective: This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients., Research Design and Methods: A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period., Results: Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of -4.3 +/- 9.9 units (-7.8 +/- 18%) compared with an increase with placebo treatment of 1.7 +/- 8.3 units (2.8 +/- 12.7%) (P = 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of -2.6 +/- 3.2 units (-7.9 +/- 23.8%) compared with an increase with placebo treatment of 1.9 +/- 5.7 units (8.8 +/- 27.1%) (P = 0.023). HbA(1c) remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (<60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P = 0.069)., Conclusions: Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.

Background: Obesity enhances hemodynamic alterations that predispose to a subsequent increase in left ventricular (LV) wall stress leading to LV hypertrophy. In obese subjects, weight reduction regresses LV mass (LVM), regardless of blood pressure. Sibutramine can increase blood pressure and heart rate, which may attenuate the reductions in LVM associated with weight loss., Methods: Outpatients (n = 184, age 18-65 y, body mass index > or =30 to <40 kg/m2) were randomly assigned to 6 months of once daily double-blind treatment with sibutramine 10 mg or 20 mg, or placebo. LV dimensions, status and function of the valves, weight loss, blood pressure, heart rate, and electrocardiogram were assessed., Results: For end point data sets, the mean +/- SD LVM index (LVM/height) changes were -3.0 +/- 11.9 g/m for placebo (n = 56), -4.4 +/- 10.7 g/m for sibutramine 10 mg (n = 61), and -4.3 +/- 10.9 g/m for sibutramine 20 mg (n = 56). The reductions observed in the sibutramine groups were statistically significant compared with baseline (P <.01), but pairwise comparison results with placebo were not statistically significant. There was no difference in overall status of the cardiac valves. A statistically significant greater weight loss was found in patients on both doses of sibutramine compared with placebo (P <.001). No statistically significant differences between the groups were observed in respect to blood pressure and electrocardiographic intervals, but a statistically significant increase in pulse rate (7 beats/min) was noted for patients with sibutramine treatment., Conclusion: A 6-month treatment with sibutramine does not affect ventricular dimensions, heart valves, and electrocardiogram variables.

Treatment of the first web injuries are based on the concept of one stage repair of the complex injuries of the hand with early motion. Radical debridement is specially important in case of muscular attrition. Fasciotomie of the first web is systematic in case of crush injuries for avoiding compartimental syndrome. For prevention of first web retraction, one or two Kirchner wires are placed in emergency between first and second metacarpal, and later a spilt in maximal anti-position of the first ray. In case of communited fractures, skeletal stabilisation use inlay internal devices, such the blocked intramedullary nail. First web reconstruction must take into consideration the cutaneous functionnal units of the hand, described by Michon. Thin and split-thickness grafts are rarely used for covering skin defects of the first web space, because their ability of retraction. Exposition of bone or tendons leads to the realisation of a flap. Soft tissue coverage must be achieved in emergency or after a second look within the first 48 hours. The kite flap is the most useful local flap for the first web space. The interosseous flap is the best choice among the regional pedicled flap. The use of the Chinese flap must be very careful, because the possibility of contusion of the radial pedicle in these types of injuries. It is only in case of contra-indication of the interosseous flap that free flaps can be realised, as the lateral arm flap or the parascapular flap. The groin flap keeps few indications for aesthetic reasons, or when regional flaps and microsurgery are contra-indicated.

We report the use of a free gracilis flap in six cases of medium size tissue loss over the ankle and foot. All the procedures were done under spinal or epidural block. A muscle flap was used twice and a musculocutaneous flap four times. The skin paddle was reliable in three cases for evaluation of the vascularity of the musculocutaneous flaps, but in one case there was necrosis of 70% of the surface. In three cases the fatty skin paddle was removed at two weeks and the entire muscle surface was mesh skin grafted. The advantages of the use of a gracilis flap are easy dissection and low donor site morbidity. This flat and thin muscle is well-suited for medium size defects from 8-15 cm. The length of the pedicle could be extended to 8 cm by dissecting it as far as the profunda femoris vessels.