Thirty-Day Morbidity and Mortality of the Laparoscopic Ileal Interposition Associated with Sleeve Gastrectomy for the Treatment of Type 2 Diabetic Patients with BMI < 35: An Analysis of 454 Consecutive Patients

Background The objective of this study was to evaluate the early results of the laparoscopic interposition of a segment of ileum associated with a sleeve gastrectomy (LII-SG) in order to treat patients with type 2 diabetes mellitus (T2DM) and BMI <35. Data regarding morbidly obese diabetic patients subjected to surgery has consistently been validated. To date, there is scarce information about morbidity and mortality related to the surgical treatment of a ""true"" typical diabetic population with BMI <35. Methods The procedures were performed in 454 patients (322 male, 132 female). Mean age was 53.6 +/- 8 years (range = 27-75). Mean BMI was 29.7 +/- 3.6 kg/m(2) (range = 19-34.8). All patients had the diagnosis of T2DM for at least 3 years. Insulin therapy was used by 45.6% of patients. Mean duration of T2DM was 10.8 +/- 5.9 years (range = 3-35). Mean hemoglobin A(1c) was 8.8 +/- 1.9%. Dyslipidemia was observed in 78.4%, hypertension in 64.8%, nephropathy in 28.6%, retinopathy in 32.6%, neuropathy in 34.6%, and coronary heart disease in 13%. Results There was no conversion to open surgery. All patients were evaluated postoperatively. Mortality was 0.4%. There were 29 major complications (6.4%) in 22 patients (4.8%) and 51 minor complications (11.2%). Reoperations were performed on 8 patients (1.7%). Twenty patients (4.4%) were readmitted to the hospital. Mean postoperative BMI was 25.8 +/- 3.5 kg/m(2). Mean fasting plasma glucose decreased from 198 +/- 69 to 128 +/- 67 mg/dl and mean postprandial plasma glucose decreased from 262 +/- 101 to 136 +/- 43 mg/dl. Conclusions The laparoscopic ileal interposition associated with a sleeve gastrectomy was considered a safe operation with low rates of morbidity and mortality in a diabetic population with BMI < 35. An early control of postprandial glycemia was observed.

Impact on Dyslipidemia of the Laparoscopic Ileal Interposition Associated to Sleeve Gastrectomy in Type 2 Diabetic Patients

Dyslipidemia is known to increase significantly the odds of major cardiovascular events in the general population. Its control becomes even more important in the type 2 diabetic (T2DM) population. Bariatric surgeries, especially gastric bypass, are effective in achieving long-term control of dyslipidemia in morbidly obese patients. The objective of the study was to evaluate the control of dyslipidemia in patients with T2DM and BMI below 30 that were submitted to the laparoscopic ileal interposition associated to sleeve gastrectomy. An observational transversal study was performed in a tertiary care hospital, between June 2005 and August 2007. Mean follow-up was 24.5 months (range 12-38). The procedure was performed in 72 patients: 51 were men and 21 were women. Mean age was 53.1 years (38-66). Mean BMI was 27 kg/m(2) (22.1-29.4). Mean duration of T2DM was 10.5 years (3-22). Mean HbA1c was 8.5%. Hypercholesterolemia was diagnosed in 68% of the patients and hypertriglyceridemia in 63.9%. Mean postoperative BMI was 21.2.kg/m(2) (17-26.7). Mean postoperative HbA1c was 6.1%, ranging 4.4% to 8.3%. Overall, 86.1% of the patients achieved an adequate glycemic control (HbA1c < 7) without anti-diabetic medication. HbA1c below 6 was achieved by 50%, 36.1% had HbA1c between 6 and 7, and 13.9% had HbA1c above 7. Total hypercholesterolemia was normalized in 91.8% and hypertriglyceridemia in 89.1% of patients. Low-density lipoprotein below 100 mg/dl was seen in 85.7%. The laparoscopic ileal interposition associated to sleeve gastrectomy was an effective operation for the regression of dyslipidemia and T2DM in a non-obese population.

Electrical burns: A retrospective analysis across a 5-year period

This study aims to review the experience, at an institution, with patients who suffered electrical burns and study the peculiar characteristics of this type of burn as well as its complications and epidemiological aspects. The study includes medical records of patients with electrical burns who were admitted to the Burn Unit of Hospital das Clinicas in Sao Paulo, Brazil, from November 2001 to October 2006. They were classified into four categories: high voltage (>= 1000 V), low voltage (<1000 V), `flash burn` (in which there is no electrical current flow through the body of the patient) and burns caused by lightning. The complications were more severe and common in the high-voltage group, while longer hospital stays and more complex surgical procedures due to the greater depth of burns were also observed in this group. High-voltage burns are mainly labour-/occupation-related. The majority of the patients were young men at the beginning of their professional lives. This factor generates an important socio-economic impact due to the high incidence of sequelae, resulting in amputations, rendering them unable to maintain their occupations. (C) 2009 Elsevier Ltd and ISBI. All rights reserved.

A low-temperature insulating phase at v=1.5 for 2D holes in high-mobility SiSi1-xGex heterostructures with Landau level degeneracy

Magneto-transport measurements of the 2D hole system (2DHS) in p-type Si-Si1-xGex heterostructures identify the integer quantum Hall effect (IQHE) at dominantly odd-integer filling factors v and two low-temperature insulating phases (IPs) at v = 1.5 and v less than or similar to 0.5, with re-entrance to the quantum Hall effect at v = 1. The temperature dependence, current-voltage characteristics, and tilted field and illumination responses of the IP at v = 1.5 indicate that the important physics is associated with an energy degeneracy of adjacent Landau levels of opposite spin, which provides a basis for consideration of an intrinsic, many-body origin.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

Creatine in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

GUALANO, B., V. DE. SALLES PAINNELI, H. ROSCHEL, G. G. ARTIOLI, M. NEVES JR, A. L. DE SA PINTO, M. E. DA SILVA, M. R. CUNHA, M. C. G. OTADUY, C. DA COSTA LEITE, J. C. FERREIRA, R. M. PEREIRA, P. C. BRUM, E. BONFA, and A. H. LANCHA JR. Creatine in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 770-778, 2011. Creatine supplementation improves glucose tolerance in healthy subjects. Purposes: The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training. Methods: A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g.d(-1)) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (Hb(A1c)). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed. Results: Twenty-five subjects were analyzed (CR: n = 13; PL: n = 12). Hb(A1c) was significantly reduced in the creatine group when compared with the placebo group (CR: PRE = 7.4 +/- 0.7, POST = 6.4 +/- 0.4; PL: PRE = 7.5 +/- 0.6, POST = 7.6 +/- 0.7; P = 0.004; difference = -1.1%, 95% confidence interval = -1.9% to -0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR = -7790 +/- 4600, PL = 2008 +/- 7614; P = 0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups. Conclusions: Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.

CD4+T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes

P>Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4-23, 45-64 and 73-95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Derivation and external validation of a simple prediction model for the diagnosis of type 2 Diabetes Mellitus in the Brazilian urban population

A risk score model was developed based in a population of 1,224 individuals from the general population without known diabetes aging 35 years or more from an urban Brazilian population sample in order to select individuals who should be screened in subsequent testing and improve the efficacy of public health assurance. External validation was performed in a second, independent, population from a different city ascertained through a similar epidemiological protocol. The risk score was developed by multiple logistic regression and model performance and cutoff values were derived from a receiver operating characteristic curve. Model`s capacity of predicting fasting blood glucose levels was tested analyzing data from a 5-year follow-up protocol conducted in the general population. Items independently and significantly associated with diabetes were age, BMI and known hypertension. Sensitivity, specificity and proportion of further testing necessary for the best cutoff value were 75.9, 66.9 and 37.2%, respectively. External validation confirmed the model`s adequacy (AUC equal to 0.72). Finally, model score was also capable of predicting fasting blood glucose progression in non-diabetic individuals in a 5-year follow-up period. In conclusion, this simple diabetes risk score was able to identify individuals with an increased likelihood of having diabetes and it can be used to stratify subpopulations in which performing of subsequent tests is necessary and probably cost-effective.

Lipopolysaccharide biosynthesis genes in koala type I Chlamydia: Cloning and characterization

We showed in 1988 that there are two strains of Chlamydia psittaci which infect the koala (Phascolarctos cinereus). In order to further investigate the role of these chlamydial strains in pathogenesis, we have attempted to identify genes of koala type I strain chlamydial which are involved in the immunogenic response, Transformation of Escherichia coli with a plasmid containing a 6.3-kb fragment (pKOC-10) of C. psittaci DNA caused the appearance of a specific chlamydial lipopolysaccharide (LPS) epitope on the host strain. The smallest DNA fragment capable of inducing the expression of chlamydial LPS was an Xbal fragment, 2.4 kb in size (pKOC-5). DNA sequence analysis of the complete fragment revealed regions of high identity, at the amino acid level, to the gseA genes of C. pneomoniae, C. psittaci 6BC and C. trachomatis, and the kdtA gene of E. coli which code for transferases catalysing the addition of 3-deoxy-D-manno-octulosonic acid (Kdo) residues to lipid A. Two open reading frames (ORFs) of 1,314 and 501 nucleotides in size, within the 2.4-kb fragment, were evident, and mRNA species corresponding to these ORFs were detected by Northern analysis. Both ORF1 and ORF2 are required for the appearance of chlamydia-specific LPS on the surface of recombinant E. coli.

Glycosaminoglycan chains from alpha(5)beta(1) integrin are involved in fibronectin-dependent cell migration

alpha(5)beta(1) integrin from both wild-type CHO cells (CHO-K1) and deficient in proteoglycan biosynthesis (CHO-745) is post-translationally modified by glycosaminoglycan chains. We demonstrated this using [(35)S]sulfate metabolic labeling of the cells, enzymatic degradation, immunoprecipitation reaction with monoclonal antibody, fluorescence microscopy, and flow cytometry. The alpha(5)beta(1) integrin heterodimer is a hybrid proteoglycan containing both chondroitin and heparan sulfate chains. Xyloside inhibition of sulfate incorporation into alpha(5)beta(1) integrin also supports that integrin is a proteoglycan. Also. cells grown with xyloside adhered on fibronectin with no alteration in alpha(5)beta(1) integrin expression. However, haptotactic motility on fibronectin declined in cells grown with xyloside or chlorate as compared with controls. Thus, alpha(5)beta(1) integrin is a proteoglycan and the glycosaminoglycan chains of the integrin influence cell motility on fibronectin. Similar glycosylation of alpha(5)beta(1) integrin was observed in other normal and malignant cells, suggesting that this modification is conserved and important in the function of this integrin. Therefore, these glycosaminoglycan chains of alpha(5)beta(1) integrin are involved in cellular migration on fibronectin.

Expression of activated mutants of the human interleukin-3/interleukin-5 granulocyte-macrophage colony-stimulating factor receptor common beta subunit in primary hematopoietic cells induces factor-independent proliferation and differentiation

To date, several activating mutations have been discovered in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Two of these, Fl Delta and 1374N, result in a 37 amino acid duplication and a single amino acid substitution in the extracellular domain of h beta c, respectively. A third, V449E, results in a single amino acid substitution in the transmembrane domain, Previous studies comparing the activity of these mutants in different hematopoietic cell lines imply that the transmembrane and extracellular mutations act by different mechanisms and suggest the requirement for cell type-specific molecules in signalling. To characterize the ability of these mutant hpc subunits to mediate growth and differentiation of primary cells and hence investigate their oncogenic potential, we have expressed all three mutants in primary murine hematopoietic cells using retroviral transduction. It is shown that, whereas expression of either extracellular hpc mutant confers factor-independent proliferation and differentiation on cells of the neutrophil and monocyte lineages only, expression of the transmembrane mutant does so on these lineages as well as the eosinophil, basophil, megakaryocyte, and erythroid lineages, Factor-independent myeloid precursors expressing the transmembrane mutant display extended proliferation in liquid culture and in some cases yielded immortalized cell lines. (C) 1997 by The American Society of Hematology.

In familial hyperaldosteronism type I, hybrid gene-induced aldosterone production dominates that induced by wild-type genes

We compared the aldosterone-producing potency of the angiotensin II-sensitive wild-type aldosterone synthase genes and the ACTH-sensitive hybrid 11 beta-hydroxylase/aldosterone synthase gene by examining aldosterone, PRA, and cortisol day-curves (2-hourly levels over 24 h) in patients with familial hyperaldosteronism type I, before and during long-term (0.8-13.5 yr) glucocorticoid treatment. In 8 untreated patients, PRA levels were usually suppressed, and aldosterone correlated strongly with cortisol (r = 0.69-0.99). Fourteen studies were performed on 10 patients receiving glucocorticoid treatment that corrected hypertension, hypokalemia, and PRA suppression in all. ACTH was markedly and continuously suppressed in 6 studies, 3 of which demonstrated strong correlations between aldosterone and PRA (r = 0.77-0.92), ACTH was only partially suppressed in the remaining 8 studies; aldosterone correlated strongly: 1) with cortisol alone in 5 (r = 0.71-0.98); 2) with cortisol (r = 0.90) and PRA (r = 0.74) in one; 3) with PRA only in one (r = 0.80); and 4) with neither PRA nor cortisol in one. Unless ACTH is markedly and continuously suppressed, aldosterone is more responsive to ACTH than to renin/angiotensin II, despite the latter being unsuppressed. This is consistent with the hybrid gene being more powerfully expressed than the wild-type aldosterone synthase genes in familial hyperaldosteronism type I.

Tube feeding with a diabetes-specific feed for 12 weeks improves glycaemic control in type 2 diabetes patients

Background and aims: Assess longer-term (12 weeks) effects of a diabetes-specific feed on postprandial glucose response, glycaemic control (HbA1c), lipid profile, (pre)-albumin, clinical course and tolerance in diabetic patients. Methods: In this randomized, controlled, double-blind, parallel group study 25 type 2 diabetic patients on tube feeding were included. Patients received a soy-protein based, multi-fibre diabetes-specific feed or isocaloric, fibre-containing standard feed for 12 weeks, while continuing on their anti-diabetic medication. At the beginning, after 6 and 12 weeks, several (glycaemic) parameters were assessed. Results: The postprandial glucose response (iAUC) to the diabetes-specific feed was lower at the 1st assessment compared with the standard feed (p = 0.008) and this difference did not change over time. HbA1c decreased over time in the diabetes-specific and not in the standard feed group (treatment*time:p = 0.034): 6.9 +/- 0.3% (mean +/- SEM) at baseline vs. 6.2 +/- 0.4% at 12 weeks in the diabetes-specific group compared to 7.9 +/- 0.3% to 8.7 +/- 0.4% in the standard feed group. No significant treatment*time effect was found for fasting glucose, insulin, (pre-) albumin or lipid profile, except for increase of HDL in the diabetes-specific group. Conclusions: The diabetes-specific feed studied significantly improved longer-term glycaemic control in diabetic patients. This was achieved in addition to on-going anti-diabetic medication and may affect clinical outcome. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Mucinous colorectal adenocarcinoma: influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis

Background Mucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed. Materials and Methods Immunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed. Results Of the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression. Conclusions Mucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.