Genomewide association study of C-peptide surfaces key regulatory genes in IndiansC

Insulin is a commonly used measure of pancreatic β-cell function but exhibits a short half-life in the human body. During biosynthesis, insulin release is accompanied by C-peptide at an equimolar concentration which has a much higher plasma half-life and is therefore projected as a precise measure of β-cell activity than insulin. Despite this, genetic studies of metabolic traits haveneglected the regulatory potential of C-peptide for therapeutic intervention of type-2 diabetes. The present study is aimed to search genomewide variants governing C-peptide levels in genetically diverse and high risk population for metabolic diseases—Indians. We performed whole genome genotyping in 877 healthy Indians of Indo-European origin followed by replication of variants with P ≤ 1 × 10−3 in an independent sample-set of 1829 Indians. Lead-associated signals were also tested in-silico in 773 Hispanics. To secure biological rationale for observed association, we further carried out DNA methylation quantitative trait loci analysis in 233 Indians and publicly available regulatory data was mined. We discovered novel lncRNA gene AC073333.8 with the strongest association with C-peptide levels in Indians that however missed genomewide significance. Also, noncoding genes, RP1-209A6.1 and RPS3AP5; protein gene regulators, ZNF831 and ETS2; and solute carrier protein gene SLC15A5 retained robust association with C-peptide after meta-analysis. Integration of methylation data revealed ETS2 and ZNF831 single-nucleotide polymorphisms as significant meth-QTLs in Indians. All genes showed reasonable expression in the human lung, signifying alternate important organs for C-peptide biology. Our findings mirror polygenic nature of C-peptide where multiple small-effect size variants in the regulatory genome principally govern the trait biology.

Risk Factors for Interstitial Cystitis in the General Population and in Individuals With Depression / 대한배뇨장애요실금학회지

PURPOSE: To identify risk factors for interstitial cystitis (IC), a chronic bladder disorder that may have a significant detrimental impact on quality of life, in the general population and in individuals with depression. METHODS: This was a comparative study using a US claims database. Adults who had records of a visit to the health system in 2010 or later were included. The outcome was the development of IC within 2 years after the index date. The index date for the general population was the first outpatient visit, and for individuals with depression, it was the date of the diagnosis of depression. IC was defined using the concepts of ulcerative and IC. We included all medical conditions present any time prior to the index visit as potential risk factors. RESULTS: The incidence of IC was higher in individuals with depression than in the general population. Of the 3,973,000 subjects from the general population, 2,293 (0.06%) developed IC within 2 years. Of the 249,200 individuals with depression, 320 (0.13%) developed IC. The characteristics of the individuals who developed IC were similar in both populations. Those who developed IC were slightly older, more likely to be women, and had more chronic pain conditions, malaise, and inflammatory disorders than patients without IC. In the general population, subjects who developed IC were more likely to have mood disorders, anxiety, and hypothyroidism. CONCLUSIONS: The incidence of IC was higher in individuals with depression. Subjects who developed IC had more chronic pain conditions, depression, malaise, and inflammatory disorders.

Screening for chronic kidney disease and its risk factors in Oghara, Nigeria: a World Kidney Day 2014 report

Background: The risk factors associated with CKD such as hypertension, diabetes and obesity remain prevalent globally, resulting in a high prevalence of CKD especially in developing countries. Screening for CKD and its' risk factors is recommended for high-risk population. This study aimed to determine the prevalence and risk factors of CKD in a semiurban community in Nigeria.Methods: A cross-sectional survey was conducted in the teaching hospital premises at Oghara, after a world kidney day (WKD) health awareness campaign was undertaken in the community. A total of 135 subjects were interviewed and the following measurements were performed: blood pressure, body mass index, blood glucose, dipstick urinalysis, serum creatinine and estimation of glomerular filtration rate (GFR) using CKDEPI.Results: Mean age was 40 ± 13 years and 69.6% of participants were young. Male to female ratio was 1:4. The prevalence of proteinuria was 4.4% while 10.7% of all subjects had CKD (GFR <60ml/min). Although 11.1% of participants were known hypertensives only 6.7% had high blood pressure on screening. Other risk factors identified were Diabetes mellitus (10.3%), family of history of hypertension (14.1%), family of history of diabetes (9.6%), family of history CKD (1.5%) and obesity (11.9%). Proteinuria, diabetes and family history of hypertension were significantly associated with CKD.Conclusions: CKD and its risk factors are common in the population.Dipstick proteinuria remains a useful and significant indicator of CKD.Community screening for the risk factors of CKD in developing countries is realistic and should be encouraged as a public health priority

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Next generation of procedural skills curriculum development: proficiency?based progression

Background: Until recently training, assessment and certification of technical procedural skills [surgical and other interventional procedures] has been a matter of subjective evaluation by a faculty or senior peer. A few new technical skills courses have begun quantifying surgical performance, however none have required benchmark scores that must be met to guarantee proficiency. Based on nearly 100 years of technical skills simulation in other high-risk sectors [aviation, military, nuclear industry, etc.], a new, comprehensive procedural skills curriculum development process, entitled 'full life-cycle curriculum development' and which uses the principles of proficiency-based progression, has been developed and implemented for the Fundamentals of Robotic Surgery [FRS] curriculum - a simulation course for technical skills with quantitative metrics

Methodology: Four consensus conferences by Delphi method, with official representatives of 14 surgical specialties that use robotic surgery was conducted to develop Outcomes Measures/metrics, Didiactic Curriculum, Simulation Content for a novel simulator, and Validation Trial. Proficiency-based progression, based upon expert performance benchmarks, was used to establish the scores which the novices must complete in order to pass

Results: An initial pilot study for validation of this new curriculum process has been completed to determine rough-ordermagnitude of parameters and usability and practicality, as well as a preliminary evaluation of suitability as an educational course. A final full validation study is in progress to confirm the initial results of both the validity and educational value of this course. A validated course for gynecologic robotic surgery has been completed and validated using the same templates as the FRS

Conclusion: The FRS use a new process [full life-cycle curriculum development with proficiency-based progression] which can be used in order to develop any quantitative procedural curriculum, through generic templates that have been developed. Such an approach will dramatically decrease the cost, time and effort to develop a new specific curriculum, while producing uniformity in approach, inter-operability among different curricula and consistency in objective assessment. This process is currently online, open source and freely available, to encourage the adoption of a scholarly and rigorous approach to curriculum development which is flexible enough to be adopted and adapted to most technical skills curriculum needs

Predicting mortality after congenital heart surgeries: Evaluation of the Aristotle and Risk Adjustement in Congenital Heart surgery-1 risk prediction scoring systems: A retrospective single center analysis of 1150 patients.

Aims and Objectives: To validate Aristotle basic complexity and Aristotle comprehensive complexity (ABC and ACC) and risk adjustment in congenital heart surgery‑1 (RACHS‑1) prediction models for in hospital mortality after surgery for congenital heart disease in a single surgical unit. Materials and Methods: Patients younger than 18 years, who had undergone surgery for congenital heart diseases from July 2007 to July 2013 were enrolled. Scoring for ABC and ACC scoring and assigning to RACHS‑1 categories were done retrospectively from retrieved case files. Discriminative power of scoring systems was assessed with area under curve (AUC) of receiver operating curves (ROC). Calibration (test for goodness of fit of the model) was measured with Hosmer‑Lemeshow modification of χ2 test. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were applied to assess reclassification. Results: A total of 1150 cases were assessed with an all‑cause in‑hospital mortality rate of 7.91%. When modeled for multivariate regression analysis, the ABC (χ2 = 8.24, P = 0.08), ACC (χ2 = 4.17, P = 0.57) and RACHS‑1 (χ2 = 2.13, P = 0.14) scores showed good overall performance. The AUC was 0.677 with 95% confidence interval (CI) of 0.61-0.73 for ABC score, 0.704 (95% CI: 0.64-0.76) for ACC score and for RACHS‑1 it was 0.607 (95%CI: 0.55-0.66). ACC had an improved predictability in comparison to RACHS‑1 and ABC on analysis with NRI and IDI. Conclusions: ACC predicted mortality better than ABC and RCAHS‑1 models. A national database will help in developing predictive models unique to our populations, till then, ACC scoring model can be used to analyze individual performances and compare with other institutes.

Prevalence of HIV and Disease Outcomes on the Medical and Surgical Wards at Kamuzu Central Hospital, Lilongwe, Malawi

Introduction: The World Health Organization (WHO) recommends HIV Counseling and Testing (HCT) in a range of clinical settings. We describe the characteristics of patients diagnosed with HIV on the medical and surgical wards at a tertiary care hospital in Malawi. Methods: Under the universal opt-out HCT protocol we characterized the number of new HIV/AIDS infections and associated clinical features among hospitalized surgical and medical patients diagnosed during the course of admission. Results: All 2985 and 3959 medical and surgical patients, respectively, admitted between April 2012 and January 2013 were screened for HCT. 62% and 89% of medical and surgical patients, respectively, had an unknown status on admission and qualified for testing. Of the patients with an unknown status, a new HIV diagnosis was made in 20% and 7% of medical and surgical patients, respectively. Of the newly diagnosed patients with a CD4 count recorded, 91% and 67% of medical and surgical patients, respectively, had a count less than 350, qualifying for ART by Malawi ART guidelines. Newly HIV-diagnosed medical and surgical patients had an inpatient mortality of 20% and 2%, respectively. Discussion: While newly diagnosed HIV-positive medical patients had high inpatient mortality and higher rates of WHO stage 3 or 4 conditions, surgical patients presented with less advanced HIV, though still meeting ART initiation guidelines. The medical inpatient wards are an obvious choice for implementing voluntary counseling and testing (VCT), but surgical patients present with less advanced disease and starting treatment in this group could result in more years of life gained.

Sensitivity of hospital-based surveillance for severe disease: a geographic information system analysis of access to care in Kilifi district, Kenya

Objective To explore the relationship between homestead distance to hospital and access to care and to estimate the sensitivity of hospital-based surveillance in Kilifi district; Kenya. Methods In 2002-2006; clinical information was obtained from all children admitted to Kilifi District Hospital and linked to demographic surveillance data. Travel times to the hospital were calculated using geographic information systems and regression models were constructed to examine the relationships between travel time; cause-specific hospitalization rates and probability of death in hospital. Access to care ratios relating hospitalization rates to community mortality rates were computed and used to estimate surveillance sensitivity. Findings The analysis included 7200 admissions (64 per 1000 child-years). Median pedestrian and vehicular travel times to hospital were 237 and 61 minutes; respectively. Hospitalization rates decreased by 21per hour of travel by foot and 28per half hour of travel by vehicle. Distance decay was steeper for meningitis than for pneumonia; for females than for males; and for areas where mothers had less education on average. Distance was positively associated with the probability of dying in hospital. Overall access to care ratios; which represent the probability that a child in need of hospitalization will have access to care at the hospital; were 51-58for pneumonia and 66-70for meningitis. Conclusion In this setting; hospital utilization rates decreased and the severity of cases admitted to hospital increased as distance between homestead and hospital increased. Access to hospital care for children living in remote areas was low; particularly for those with less severe conditions. Distance decay was attenuated by increased levels of maternal education. Hospital-based surveillance underestimated pneumonia and meningitis incidence by more than 45and 30; respectively

Transcriptoma en mexicanos: metodología para analizar el perfil de expresión genética de gran escala en muestras simultáneas de tejido muscular, adiposo y linfocitos obtenidas en un mismo individuo / Transciptome among Mexicans: a large scale methodology to analyze the genetics expression profile of simultaneous samples in muscle, adipose tissue and lymphocytes obtained from the same individual

Objetivo: Describir la metodología de análisis de múltiples transcritos con técnicas de microarreglo en biopsias simultáneas de tejido muscular, adiposo y sangre en un mismo individuo, como parte de la estandarización del estudio GEMM (Genética de las Enfermedades Metabólicas en México). Material y métodos: Se incluyó a cuatro sujetos con índice de masa corporal (IMC) entre 20 y 41. Se registró estatura, talla y composición corporal. Se realizó biopsia muscular (vasto lateral), de tejido adiposo subcutáneo y muestra de sangre completa. El ARN total fue extraído de los tejidos y amplificado para análisis de microarreglos. Resultados: De 48 687 potenciales transcritos, 39.4% fue detectable en al menos uno de los tejidos. La expresión de leptina no fue detectable en linfocitos, débilmente expresada en músculo, alta expresión en el tejido adiposo y correlacionó con el IMC. El GLUT4 también ilustra la especificidad para el músculo sin verse afectado por el IMC. La concordancia en la expresión de transcritos fue 0.70 (p<0.001) para los tres tejidos. Conclusiones: Fue factible cuantificar simultáneamente la expresión genética de miles de transcritos, hubo concordancia en la expresión entre diferentes tejidos obtenidos en un mismo individuo, y confiabilidad del método al reproducir las relaciones biológicas esperadas. El estudio GEMM podrá analizar las correlaciones de los transcritos expresados dentro de un órgano y luego entre diferentes tejidos, y proveerá endofenotipos cuantitativos novedosos que proporcionarán un amplio panorama de información sobre las enfermedades metabólicas, incluyendo obesidad y diabetes tipo 2.

OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

Reproducibilidad y sensibilidad del cuestionario Impacto del peso en la calidad de vida en mexicanos obesos / Reproducibility and sensitivity of the impact of weight on quality of life questionnaire among obese Mexicans

Objetivo: Determinar si el cuestionario “Impacto del peso en la calidad de vida” (IWQOL) es reproducible y sensible para identificar diferencias entre las clases de obesidad establecidas por la Organización Mundial de la Salud. Métodos: El IWQOL fue traducido al castellano de acuerdo a la usanza del lenguaje en México pero manteniendo un vocabulario amplio para América Latina. Investigamos la reproducibilidad del cuestionario por el método de prueba-reprueba (n=82, IMC=37.8±8.4), la sensibilidad para identificar diferencias entre los grados de la obesidad (n=105, IMC=35.1±9.5) y la sensibilidad para detectar diferencias después de recibir algún tratamiento para la pérdida del peso (n=40, IMC=39.2±7). Resultados: El IWQOL mostró buena reproducibilidad y sensibilidad para identificar diferencias entre grupos de obesos y cambios luego de tratamiento. Todos los dominios fueron reproducibles (criterio a priori: la diferencia entre prueba re-prueba no debía ser mayor de 5 puntos porcentuales) y tuvieron alta validez interna (coeficiente alfa de Cronbach>0.92 para todos los dominios). El IWQOL detectó diferencias entre los grupos divididos por la severidad de la obesidad, siendo los más afectados aquellos con IMC>45. Los sujetos sometidos a tratamiento perdieron 6.4 kg (IC95%=4.6-8.2) durante un periodo de 2.70±1 meses e incrementaron la calificación en todos los dominios, excepto el correspondiente a “trabajo”. Conclusiones: El cuestionario IWQOL es una herramienta confiable y sensible que se puede utilizar para la investigación de la calidad de vida en mexicanos y probablemente en la mayoría de las poblaciones latinoamericanas. Nuestro estudio es el primero envalidar el IWQOL en México.

OBJECTIVE: Determine if the Spanish version of the IWQOL (Impact of Weight on Quality of Life) questionnaire is reproducible and sensitive to detect differences among WHO's classification of obesity. METHODS: The IWQOL was translated into Spanish and adapted to the Mexican context while maintaining a wide comprehensive vocabulary applicable to Latin American countries. We measured reproducibility using a test-retest method (n=82, BMI 37.8+/-8.4), sensitivity to detect differences between types of obesity (n=105, BMI 35.1+/-9.5), and sensitivity to detect differences after treatment for weight loss within groups (n=40, BMI 39.2+/-7). RESULTS: The IWQOL questionnaire was reliable and sensitive enough to detect differences among and within groups. All domains were highly reproducible (scores differed by less than 2 points) and had high internal validity (Cronbach alpha coefficient >0.92 for all scales). The IWQOL detected differences between groups stratfied by severity of obesity, the lowest score was for BMI >45. Subjects who underwent weight loss treatment and lost 6.4 kg (95% CI 4.6, 8.2) during a period of 2.70+/-1 month had an improvement in all scales except for the [quot ]Work[quot ] domain. CONCLUSIONS: The IWQOL questionnaire is a reliable and sensitive tool that can be used for research purposes in Mexico and the Latin America region. Our study validates the use of IWQOL among Mexican subjects.

Objetivos moleculares para diseñar nuevos fármacos para el tratamiento de la diabetes tipo 2 y la obesidad: [revisión] / Molecular targets for new drug discovery to treat type 2 diabetes and obesity: [review]

Current strategies to treat type 2 diabetes (DMT2) include reducing insulin resistance using glitazones, supplementing with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors. In all of these areas, new generations of molecules with improved efficacy and safety profiles, are being investigated. Promising biological targets are rapidly emerging such as the role of lipotoxicity as a cause of glucometabolic insulin resistance, leading to a host of new molecular drug targets such as AMP-activated protein kinase (AMPK) activators, recombinant adiponectin derivatives, and fatty acid synthase (FAS) inhibitors. Insulin action can be enhanced in muscle, liver and fat, with small-molecule activators of the insulin receptor or inhibitors of protein tyrosine phosphatase (FTP)-IB. Defective glucose-stimulated insulin secretion by pancreatic B-cells could be alleviated with recombinant glucagon-like peptide (GLP-1) or agonists to the GLP-1 receptor. This review presents a new approach for obesity and DMT2 drug discovery through pharmacogenomics. Several compounds have already been validated through genetic engineering in animal models or the preliminary use of therapeutic compounds in humans.

Macrófagos, inflamación, tejido adiposo, obesidad y resistencia a la insulina / Macrophages, inflammation, adipose tissue, obesity and insulin resistance

La obesidad se asocia con un estado inflamatorio implicado en el desarrollo de aterosclerosis y resistencia a la insulina. Los macrófagos son claves en la génesis de estos procesos. La obesidad induce la acumulación de macrófagos en el tejido adiposo. Los macrófagos producen muchas de las moléculas inflamatorias secretadas por el tejido adiposo. Las proteínas quimioatrayentes de monocitos (MCP) y sus receptores son fundamentales en la respuesta inflamatoria y en el reclutamiento de células inmunes en sitios de inflamación. La expresión en el tejido adiposo de una MCP, la quimiocina del ligando 2 del motif C-C (CCL2 o MCP1), está incrementada en proporción a la adiposidad. El receptor 2 de quimiocina del motif C-C (CCR2) regula el reclutamiento y quimiotaxis de monocitos y macrófagos, es necesario para las respuestas inflamatorias dependientes de macrófagos y para el desarrollo de aterosclerosis. Ya que el receptor CCR2 regula las respuestas inflamatorias locales, se ha postulado que las MCP, actuando a través de su receptor CCR2, podrían regular la inflamación inducida por la obesidad en el tejido adiposo. Este documento se enfoca en dilucidar los mecanismos moleculares y genéticos que permiten reclutar y retener macrófagos en el tejido adiposo.

Obesity is associated with a complex systemic inflammatory reaction that has been associated with the development of atherosclerosis and insulin resistance. Obesity also induces macrophage accumulation in adipose tissue. Macrophages produce many of the pro inflammatory molecules released by adipose tissue and have been implicated in the development of obesity-induced adipose tissue inflammation. Monocyte chemoattractant proteins (MCPs) and their receptors play key roles in the development of inflammatory responses and are crucial for the recruitment of immune cells towards inflammation sites. Adipose tissue expression of at least 1 MCP, C-C motif chemokine ligand-2 (CCL2 or MCP1), increases in proportion to adiposity. The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Because CCR2 regulates monocyte and macrophage chemotaxis and local inflammatory responses, it has been hypothesized that monocyte chemoattractant molecules acting through CCR2 might regulate obesity-induced inflammation in adipose tissue. Our study focuses on the molecular and genetic mechanisms that recruit and retain macrophages in adipose tissue.

El grado de obesidad modifica la respuesta de disminución de circunferencia de cintura en pacientes que reciben 15 mg diarios de sibutramina: estudio abierto sobre tolerancia y efectividad de la sibutramina / Patients with type III obesity given sibutramine 15 mg/day lose weight in amounts proportional to those in types I and II, but waist circumferences does not decrease proportionally

Objetivo. Los pacientes con sobrepeso y las clases de obesidad I, II, III presentan diferente etiología, comorbilidad, efectos metabólicos y diferente respuesta terapéutica. En este análisis evaluamos el efecto del grado de obesidad sobre la disminución del índice de masa corporal (IMC) y la circunferencia de cintura (CC) eficacia y tolerancia de sibutramina 15mg al día. Material y métodos. Se analizó una base de datos de una muestra de 701 sujetos colectados de 47 clínicas. Los sujetos recibieron tratamiento con 15 mg de sibutramina al día. Se registró el peso, estatura y la CC en las visitas basal, 4 y 8 semanas. Resultados. Los pacientes con diferentes grados de obesidad disminuyeron proporcionalmente el IMC (p = 0.86), pero los sujetos con obesidad clase III mostraron menor disminución de la CC (p = 0.003) que los otros grupos. Los eventos adversos fueron pocos, y de menor frecuencia con grados mayores de obesidad. Discusión. La disociación de disminución de IMC y la CC puede estar relacionada al control ejercido por el sistema simpático de acuerdo con el grado de obesidad, además de la biodistribución de sibutramina. Los sujetos con IMC mayor de 40 necesitan mayor dosis para alcanzar proporcionalmente la pérdida de grasa abdominal de los otros grupos de obesos.

OBJECTIVE: The etiology, comorbidity, metabolism, and treatment response vary among overweight and obesity types I, II and III individuals. We assessed the association between obesity type with body mass index, waist circumference and tolerance to a daily dose of 15 mg of sibutramine. MATERIALS AND METHODS: A sample of 701 individuals recruited from 47 health centers was analyzed. All subjects received 15 mg of sibutramine daily for 8 weeks. Weight, height, and waist circumference were measured at day 0 and weeks 4 and 8. RESULTS: Patients in all obesity types lost proportional amounts of weight (p=0.86), but those in type IIl obesity had a smaller reduction in waist circumference than those in types I and 1 (p=0.003). Side effects of sibutramine were rarely observed. Subjects with type III obesity exhibited even fewer side effects. CONCLUSIONS: The lack of association between weight reduction and decreased waist circumference across obesity types could be related to differences in the sympathetic nervous system or to sibutramine biodistribution. Subjects with body mass index greater than 40 Kg/ m(2) required a higher dose of sibutramine in order to loose the same proportion of abdominal fat as those in other types of obesity.

Epidemiología clínica del estado prediabético / Clinical epidemiology of the prediabetic state

La diabetes tipo 2 (DMT2) es un padecimiento muy común del metabolismo de los carbohidratos y los lípidos. La obesidad es un factor de riesgo significativo para el desarrollo de la diabetes tipo 2. La DMT2 es un factor de riesgo ampliamente reconocido para el desarrollo de la enfermedad arterial coronaria (EAC). Los pacientes con DMT2 tienen un incremento 2 a 4 veces mayor de cursar con EAC y un incremento 4 veces superior en el índice de mortalidad secundario a EAC. El estudio UKPDS y otros más han demostrado una mejoría significativa en el inicio y curso de las complicaciones microvasculares de la diabetes con un control glucémico apropiado. Sin embargo, esta aseveración no parece ser cierta con respecto a las complicaciones macrovasculares, ya que para ellas no existe una evidencia certera de una mejoría con un control apropiado en los niveles de glucosa en ayunas. Por lo anterior, es un hecho que un control intensivo del paciente diabético conlleva a un efecto mucho más modesto en reducir las complicaciones macrovasculares que las microvasculares. Esta aparente falta de benéficos en el paciente diabético al que se le ha mejorado su control glucémico ha dado lugar a intentar diferentes enfoques. Entre ellos se encuentra el que pretende prestar mayor atención al paciente obeso, prediabético caracterizado por la presencia de resistencia a la insulina. Esta última se asocia a un número significativo de anormalidades protrombóticas y proinflamatorias, que incluyen un exceso de grasa corporal, que podrían jugar un papel causal en el desarrollo de la enfermedad cardiovascular. Por lo dicho, el tratamiento de la obesidad y la prevención del desarrollo de la diabetes tipo 2 parecen ser estrategias prioritarias para prevenir o retardar la aparición de las enfermedades cardiovasculares.

Entendiendo las causas de la obesidad a traves de la biologia celular del adiposito

La obesidad es un área multidisciplinaria, cuya biología abarca: 1) los mecanismos fundamentales sobre la regulación del balance energético; 2) las bases genómicas para el desarrollo de la obesidad, 3) las vías celulares de las funciones del tejido adiposo; 4) la descripción molecular del estado obeso; 5) las consecuencias patológicas de la obesidad; 6) las bases fisiológicas para las estrategias de tratamiento. El tejido adiposo es reconocido hoy en día como un órgano endocrino clave, cuya comunicación amplia es efectuada tanto con el cerebro como con tejidos periféricos a través de estas adipocinas. La obesidad es caracterizada por una inflamación moderada y el adipocito parece ser el sitio principal de este estado inflamatorio, que lo estimula a producir citocinas, quimiocinas, proteínas de fase aguda, y factores angiogénicos. En este artículo, discutiremos las vías de señalizaciones celulares y moleculares que se encuentran en las intersecciones de los caminos inflamatorios y metabólicos que contribuyen al desarrollo de la diabetes y la disfunción endotelial a través de un exceso de grasa corporal. También nos atrevemos a sugerir varios modelos que pretenden explicar la integración de las vías inflamatorias y metabólicas dentro del contexto de las enfermedades del metabolismo y la obesidad.

Obesity is a multidisciplinary topic, the biology of which includes: 1) the f fundamental mechanisms of energy balance and its regulation; 2) the genomic basis for the development of obesity; 3) the cellular pathways of adipose tissue function; 4) the molecular description of the obese state; 5) the pathological consequences of obesity; 6) the physiological basis for treatment strategies. Adipose tissue is now recognized as a key endocrine organ, communicating both with the brain and peripheral tissues through the adipokines. Obesity is characterized by mild inflammation, and the adipocyte may be the main locus of the inflammatory state, producing cytokines, chemokines, acute-phase proteins and angiogenic factors. In this article, we discuss the molecular and cellular signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes and endothelial dysfunction through an excess of body fat. We dare to suggest several models for the integration of inflammatory and metabolic pathways in metabolic disease and obesity.

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 umol/l and Group II comprised patients with serum creatinine concentration of 600 umol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years); (p < 0.01) patients, and the mean total creatinine clearance of Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer are in progress.

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom Hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89 percent being less than 60 years of age compared to 40 percent at NCH (p<0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI than at NCH but the numbers were small (p<0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p<0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76 percent v 19 percent on haemodialysis). At UHWI, CAPD was not available and 45 percent of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

Cytomegalovirus infection in renal transplantation

Three case reports of cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropossitive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortalitiy. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection