Pancreas and islet transplantation in patients with diabetes mellitus

Pancreas and kidney transplants have specific indications, benefits and risks. The procedure has become more common and more often as long-term success has improved and risks have decreased. Compared with a patient being on dialysis, simultaneous pancreas-kidney transplant offers a distinct advantage when it comes to mortality, quality of life and diabetic complications. Since there can be a living-donor kidney transplant,, a possibly similar patient and graft survival by 10 years follow-up, this procedure should be considered. Pancreas after kidney transplants, when successful, can improve microvascular complications compared with kidney transplant alone, but immediate mortality may be higher. Solitary pancreas transplantation can improve the quality of life in selected patients, but it may also increase the immediate risk of mortality due to the complexity of the surgery and the risks of immunosupression. The results of Islet transplantation differ from the higher metabolic performance achieved by whole pancreas allotransplantation and its applicability is limited to selected adult diabetic patients.     

Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C

OBJECTIVES: Hepatic steatosis (HS) has been related to obesity and fibrosis in chronic hepatitis C (CHC). The aim of this study was to determine the role of leptin system in HS development. METHODS: Patients (n = 131) with biopsy-proven CHC, positive HCV RNA, and raised ALT were enrolled. Body mass index, percentage of body fat by skin fold measurement, and bioelectrical impedance analysis was calculated and serum leptin concentration measured. Intrahepatic HCV RNA, HS, necroinflammatory activity, and fibrosis were determined in liver biopsy tissue. RESULTS: HS was present in 63 patients (48.1%). Steatosis was evident in 32 of 91 patients (35.2%) infected with genotype 1 and in 22 of 27 patients (81.5%) with genotype 3a (p < 0.001). In patients infected by genotype 3a, HS correlated significantly with intrahepatic HCV RNA load (r = 0.78; p < 0.001). However, in genotype 1, HS was associated with host factors such as leptin, body mass index, percentage of body fat, and visceral obesity. Multivariate analysis showed genotype (OR = 11.54, 95% CI = 1.13-117.14, p = 0.038), leptin levels (OR = 1.09, 95% CI = 1.03-1.17, p = 0.008) and fibrosis (OR = 9.86, 95% CI = 2.11-5.86, p = 0.03) as independent variables of HS development. CONCLUSIONS: Hepatic steatosis was related to genotype, fibrosis degree, and serum leptin levels. Genotype 3 seems to have a viral specific steatogenic effect. Leptin seems to be a link between obesity and steatosis development in CHC genotype 1-infected patients.     

N-Acetyl-cysteine modulates inducible nitric oxide synthase gene expression in human hepatocytes

BACKGROUND/AIMS: A major role has been described for inducible nitric oxide (NO) synthase in several chronic inflammatory liver diseases. N-Acetyl-cysteine (NAC) is a sulfhydryl donor molecule with antioxidant and antiinflammatory effects. It attenuates NO generation following lipopolysaccharide injection in rats. Our goal was to study the effect of NAC on NO synthase induction in hepatocytes in response to proinflammatory cytokines. METHODS: The effect of NAC on NO synthase induction was studied in the human hepatocyte cell lines HepG2 and 2.2.15 treated with a mixture of proinflammatory cytokines. Interactions between NAC and cytokines on nuclear factor-kappaB (NF-kappaB) activation and NO synthase promoter transactivation were investigated. RESULTS: NAC dose-dependently modulated the induction of NO synthase mRNA expression, the release of nitrites and the formation of NF-kappaB binding complexes in cytokine-treated hepatocytes. NAC also reduced the transactivation of the NO synthase promoter. CONCLUSIONS: Our data show that exposure of hepatocytes to NAC modulated NO synthase expression and NF-kappaB activity, the key responses of the hepatocyte to inflammatory mediators. These data constitute preliminary evidence that NAC might have hepatoprotective actions of potential relevance in chronic inflammatory liver diseases, mediated partially through the modulation of NO production.     

Resection of metastatic pulmonary lesion of ossifying fibromyxoid tumor extending into the left atrium and ventricle via pulmonary vein.

The ossifying fibromyxoid tumor (OFMT) of soft parts is a rare soft tissue neoplasm of uncertain lineage. The most common metastases are found in the lung. Herein, we present the first case report of pulmonary metastasis of ossifying fibromyxoid tumor with intracardiac extension, which was resected carefully using cardiopulmonary bypass and cardiac arrest. Subsequently pulmonary left lower lobectomy was performed. The patient recovered uneventfully and was discharged in after a few days. Recently, OFMT has been considered as a tumor of intermediate malignancy. We recommend wide surgical excision of primary tumor and radiotherapy. Early follow-up is mandatory.     

Respiratory damage in children exposed to urban pollution

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.     

Additive effects of insulin-sensitizing and anti-androgen treatment in young,nonobese women with hyperinsulinism,hyperandrogenism, dyslipidemia,and anovulation

The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyperandrogenism and insulin resistance. We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16; monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At baseline, there were no endocrine-metabolic differences among treatment groups. Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly ovulation rates increased after 9 months to 75 and 92%, respectively, with metformin alone or with combined therapy, but were unimproved with flutamide alone. All treatments were well tolerated. In conclusion, combined anti-androgen and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia, and dyslipidemia. The data from this small study suggest that dyslipidemia is secondary to excess androgen action in concert with the hyperinsulinemia associated with insulin resistance. In contrast, anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia.     

Adolescent Substance Use and Sensation-Seeking on Sexual Behaviors Among Young Adults from Continuation High Schools

Background: Youth from continuation high schools report greater substance use and sensation-seeking than youth from regular high schools, yet their long-term consequences on age at sexual onset and the number of sexual partners are unknown. Objective: To examine substance use, sensation-seeking and sexual behaviors by gender and race/ethnicity and the effects of substance use and sensation-seeking in adolescence on age at sexual initiation and numbers of sexual partners by young adulthood. Methods: Baseline and 4-year follow-up data on youth from 14 continuation high schools in Southern California who participated in a drug abuse prevention intervention were analyzed. Structural equation modeling assessed whether or not substance use or sensation-seeking in adolescence predicted age at sexual onset and numbers of sexual partners by young adulthood. Results: Latinos had lower sensation-seeking and frequency of substance use and a later age at sexual onset than non-Latinos. Males were more likely than females to have multiple lifetime and recent sexual partners. The effects of adolescent substance use on the number of sexual partners by young adulthood were mediated fully by their age at sexual initiation. Sensation-seeking had no direct or indirect effects on sexual behaviors. Conclusions/Importance: Factors leading to and actual sexual risk behaviors among youth from continuation high schools vary by race/ethnicity and gender. Targeting these antecedent factors by race/ethnicity and gender may improve prevention efforts.     

La grasa epicárdica se relaciona con la visceral,el síndrome metabólico y la resistencia a la insulina en mujeres menopáusicas

Introduction and objectives

Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women.

Methods

A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis.

Results

A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm ²; P = .03).

Conclusions

Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women.Full English text available from:www.revespcardiol.org/en     

Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study

Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P?P?=?0.0007), higher hemoglobin levels (P?=?0.0004), higher frequency of the microgranular morphology (M3v) subtype (P?=?0.03), and the short PML/RARA (BCR3) isoform (P?FLT3-ITD^positive patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD^negative patients (82 %) (P?=?0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17–4.89; P?=?0.017). Nevertheless, complete remission (P?=?0.07), disease-free survival (P?=?0.24), and the cumulative incidence of relapse (P?=?0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.