Identification of Compound Heterozygous EVC2 Gene Variants in Two Mexican Families with Ellis-van Creveld Syndrome.

BACKGROUND: Ellis-van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature, polydactyly, dystrophic nails, oral defects, and cardiac anomalies. It is caused by pathogenic variants in the EVC or EVC2 genes. To obtain further insight into the genetics of EvCS, we identified the genetic defect for the EVC2 gene in two Mexican patients. METHODS: Two Mexican families were enrolled in this study. Exome sequencing was applied in the probands to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in the parents. Finally, a prediction of the three-dimensional structure of the mutant proteins was made. RESULTS: One patient has a compound heterozygous EVC2 mutation: a novel heterozygous variant c.519_519 + 1delinsT inherited from her mother, and a heterozygous variant c.2161delC (p.L721fs) inherited from her father. The second patient has a previously reported compound heterozygous EVC2 mutation: nonsense mutation c.645G > A (p.W215*) in exon 5 inherited from her mother, and c.273dup (p.K92fs) in exon 2 inherited from her father. In both cases, the diagnostic was Ellis-van Creveld syndrome. Three-dimensional modeling of the EVC2 protein showed that truncated proteins are produced in both patients due to the generation of premature stop codons. CONCLUSION: The identified novel heterozygous EVC2 variants, c.2161delC and c.519_519 + 1delinsT, were responsible for the Ellis-van Creveld syndrome in one of the Mexican patients. In the second Mexican patient, we identified a compound heterozygous variant, c.645G > A and c.273dup, responsible for EvCS. The findings in this study extend the EVC2 mutation spectrum and may provide new insights into the EVC2 causation and diagnosis with implications for genetic counseling and clinical management.

[Study Plan 2016 of the licentiate of medical surgery of the faculty of higher studies iztacala]. / Plan de Estudios 2016 de la Licenciatura de Médico Cirujano de la Facultad de Estudios Superiores Iztacala.

The 2016 undergraduate medical degree curriculum at the Facultad de Estudios Superiores Iztacala of the Universidad Nacional Autónoma de México (UNAM) is presented. It is the result of a long institutional reflection and academic dialog process of approximately three years, which culminated in its approval by UNAM's Academic Council for the Biology, Chemistry, and Health Sciences areas on January 25, 2016. Its most relevant characteristics are: modular organization, four knowledge areas (biomedical, methodological, socio-psychological, and humanistic and medical practice), and new modules such as Seminar of socio-psycho-biological integration; Genetics and molecular biology; Biochemistry and cellular biology; Pharmacological basis of therapeutics; Infectious diseases, microbiology and parasitology; Medical ethics; Public health; and Evidence-based medicine - clinical epidemiology. To achieve a more flexible curriculum, optional modules were included. To make possible the curricular change, improving the teaching strategies, innovating the learning assessment methods, supporting the training and updating of the teaching staff, and establishing a curriculum development committee for following up and evaluating the program, are necessary. Curricular changes are difficult and complex processes; they suppose challenges and opportunities. It is mandatory to plan them carefully and sensitively to allow a successful transition and avoid conflicts for the students, the teachers and the institution.

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients.

BACKGROUND: A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. METHODS: Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 µmol/L), NE (1.0 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L), and from five nonobese and normotensive controls treated with DA (1 µmol/L), NE (1 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L). RESULTS: A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. CONCLUSION: These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

Comparative study of enalapril vs. losartan on residual renal function preservation in automated peritoneal dialysis. A randomized controlled study.

BACKGROUND: Residual renal function (RRF) is an important determinant of mortality and morbidity in patients receiving peritoneal dialysis (PD). Recent studies have shown a positive effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) on RRF in PD patients. OBJECTIVE: To compare enalapril and losartan for RRF preservation in automated peritoneal dialysis (APD) patients. MATERIAL AND METHODS: An open label randomized controlled trial (RCT) with a 12 month follow-up period was conducted to compare the effect of enalapril vs. losartan on RRF preservation in 60 APD patients. Measurements were done at the start of the study (baseline), 3, 6, 9, and 12 months. A historical control group (HCG) without treatment was included to assess the natural history of RRF loss. RESULTS: RRF in the enalapril group dropped from 3.65 +/- 1.6 (baseline) to 2.36 +/- 0.38 mL/min/1.73 m2 (12 months). In the losartan group RRF was reduced from 4.1+/- 2.01 (baseline) to 2.54 +/- 0.47 mL/min/ 1.73 m2 (12 months). There were not significant differences between the two groups regarding RRF at 12 months. In the HCG, RRF declined from 3.68 +/- 0.48 to 1.4 +/- 0.29 mL/min/ 1.73 m2 (12 months). RRF in the HCG was significantly lower than RRF in the two treated groups at 12 months (P < 0.05). CONCLUSIONS: There was not significant difference on RRF preservation between enalapril and losartan groups. Comparing these results to those of the HCG suggests that the treatment with any of the drugs is useful in preserving RRF.

[Medical students' pleasure for participating in peer assessment]. / Agrado de los estudiantes de medicina con la evaluación por pares.

OBJECTIVE: to explore the agreement of medical students (MS) with the statement "I liked participating in my peers' assessment" and the explanations why. METHODS: the peer assessment of 411 MS who participated consisted in assessing audiovisual lectures presented by their classmates using rubrics. Then, they classified their grade of agreement with the statement "I liked participating in my peers' assessment" and briefly explained why. An analysis of content was performed, response categories were classified, and a simple count of the number of responses in each category was done. RESULTS: most of the MS (68 %) liked participating in peer assessment completely or partially. The major negative explanations were the concern that affective considerations would influence the grades (18 %), and the perception of unfair assessments (12.2 %). The positive ones were the perception of a more fair assessment (11 %), and the idea that it provides feedback for improvement (9.5 %). CONCLUSIONS: knowing the explanations given by the MS to support their agreement with the pleasure for participating in peer assessment allows a more adequate approach to conflicts.

Assessing creatinine clearance from modification of diet in renal disease study equations in the ADEMEX cohort: limitations and potential applications.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine and dialysate collections provide accepted means to assess adequacy in peritoneal dialysis (PD). Recent publications suggest that creatinine clearance (CrCl) estimated from the Modification of Diet in Renal Disease (MDRD) equations (eCrCl) accurately approximates measured CrCl (mCrCl) derived from 24-hour collections of urine and dialysate and might serve as an alternative means to assess small-solute clearance and adequacy in PD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Post hoc analysis of data from patients enrolled in ADEMEX was used to assess agreement between mCrCl and eCrCl derived by four- and six-variable MDRD equations (4V-MDRDE and 6V-MDRDE, respectively). Additionally, associations among mCrCl, eCrCl, and survival were determined. RESULTS: Acceptable precision was observed between mCrCl and 4V-MDRDE-eCrCl and 6V-MDRDE-eCrCl for the entire cohort. Precision was markedly diminished when analysis was limited to functionally anuric patients with mCrCl < 12 ml/min per 1.73 m². Although there was no association between survival and mCrCl, for every 1-ml/min per 1.73 m² increase in 4V- and 6V-MDRDE-eCrCl, there was a 6% and 4% increase in risk of death, respectively. There was a negative association between MDRDE-eCrCl and creatinine appearance rates, suggesting MDRDE-eCrCl is significantly confounded by individual differences in muscle mass. CONCLUSIONS: MDRDE-eCrCl provides demographically comparable values to 24-hour urine and dialysate collections across the ADEMEX cohort. However, MDRDEs should not be used to assess small-solute removal or adequacy in individual PD patients or to predict outcome in any cohort of patients over narrow ranges of limited clearance.

[Academic performance and problem-based learning acceptance in medical students]. / Desempeño académico y aceptación del aprendizaje basado en problemas en estudiantes de medicina.

OBJECTIVE: To measure the acceptance of problem based learning (PBL), to find out if they consider that spending extra-time is worthy, how they perceive their own learning, and how it correlated with other learning parameters. METHODS: After exposure to PBL during one semester, a cross sectional survey based on Likert-type scale was conducted to measure the students' opinion about PBL acceptance and perception of their own learning. The sample was 268 (65%) females and 143 (35%) males from the 3rd semester of the medical school. The Spearman's correlation was used for analysis. RESULTS: PBL was considered to be useful or very useful for their learning to 89% of the students. The PBL used longer time working after the classroom activities. The extra-time spent in the course was considered worthy by 77%. Perception of their own learning correlated with the marks that they obtained (rho=0.202, p<0.0001), and with the acceptance of PBL (rho=0.291, p<0.0001). CONCLUSIONS: Students' acceptance of PBL was corroborated. Perception of a better learning correlated with higher marks and, with better acceptance of PBL and with the perception that the additional time spent was worth while.

NT-proBNP, fluid volume overload and dialysis modality are independent predictors of mortality in ESRD patients.

BACKGROUND: N-terminal fragment of B-type natriuretic peptide (NT-proBNP) is a marker of both fluid volume overload and myocardial damage, and it has been useful as a predictor of mortality in patients with end-stage renal disease (ESRD). It has been suggested that continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and haemodialysis (HD) may have different effects on fluid volume and blood pressure control; however, whether the independent predictive value of NT-proBNP for mortality is preserved when analysed in conjunction with fluid overload and dialysis modality is not clear. METHODS: A prospective multicentre cohort of 753 prevalent adult patients on CAPD, APD and HD was followed up for 16 months. Plasmatic levels of NT-proBNP, extracellular fluid volume/total body water ratio (ECFv/TBW) and traditional clinical and biochemical markers for cardiovascular damage risk were measured, and their role as predictors of all-cause and cardiovascular mortality was analysed. RESULTS: NT-proBNP level, ECFv/TBW and other cardiovascular damage risk factors were not evenly distributed among the different dialysis modalities. NT-proBNP levels and ECFv/TBW were correlated with several inflammation, malnutrition and myocardial damage markers. Multivariate analysis showed that NT-proBNP levels and ECFv/TBW were predictors of both all-cause and cardiovascular mortality, independently of dialysis modality and the presence of other known clinical and biochemical risk factors. CONCLUSIONS: NT-proBNP is a reliable predictor of death risk independently of the effect of dialysis modality on fluid volume control, and the presence of other clinical and biochemical markers recognized as risk factors for all-cause and cardiovascular mortality. NT-pro-BNP is a good predictor of mortality independently of fluid volume overload and dialysis modality.

[Feasibility of implementing a learning based problem solving and peer evaluation approach among medical students in Mexico]. / Aceptación del aprendizaje basado en problemas y de la evaluación entre pares por los estudiantes de medicina.

OBJECTIVE: Assess the degree to which medical students accept and consider useful the techniques of problem based learning (PBL) and evaluation among peers. Analyze the association between the number of PBL clinical cases reviewed and the students' perception about their own learning in a basic course. METHODS: A questionnaire was administered to 334 students enrolled in the third semester of medical school (Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México). Questions included acceptability of PBL, peer evaluation, and their perception about the usefulness of these techniques after having used them during the school year. We used a Likert scale to measure opinions on the degree of usefulness of the PBL, perception of their own learning, and the acceptance of the notion that evaluation activities evaluation among peers promote justice and favor the student's character formation. We measured the association of these variables with the number of clinical cases studied using Spearman's rank correlation coefficient. RESULTS: Most of the students considered that PBL method is useful (82%) and that evaluation activities among peers promote justice and character formation (70%). Students who reviewed more PBL cases considered the PBL activities more useful (rho = 0.489, p < 0.0001), and perceived that they achieved a better learning experience (rho = 0.200, p < 0.0001). CONCLUSIONS: Results show a fair acceptance by the students of the PBL method and activities of peer evaluation. The number of clinical cases reviewed during the course correlated with considering the PBL to be a useful method and perceiving a better learning experience. Our results support the inclusion of PBL and peer evaluation in the medical school curricula.

Icodextrin improves metabolic and fluid management in high and high-average transport diabetic patients.

BACKGROUND: Icodextrin-based solutions (ICO) have clinical and theoretical advantages over glucose-based solutions (GLU) in fluid and metabolic management of diabetic peritoneal dialysis (PD) patients; however, these advantages have not yet been tested in a randomized fashion. OBJECTIVE: To analyze the effects of ICO on metabolic and fluid control in high and high-average transport diabetic patients on continuous ambulatory PD (CAPD). PATIENTS AND METHODS: A 12-month, multicenter, open-label, randomized controlled trial was conducted to compare ICO (n = 30) versus GLU (n = 29) in diabetic CAPD patients with high-average and high peritoneal transport characteristics. The basic daily schedule was 3 x 2 L GLU (1.5%) and either 1 x 2 L ICO (7.5%) or 1 x 2 L GLU (2.5%) for the long-dwell exchange, with substitution of 2.5% or 4.25% for 1.5% GLU being allowed when clinically necessary. Variables related to metabolic and fluid control were measured each month. RESULTS: Groups were similar at baseline in all measured variables. More than 66% of the patients using GLU, but only 9% using ICO, needed prescriptions of higher glucose concentration solutions. Ultrafiltration (UF) was higher (198 +/- 101 mL/day, p < 0.05) in the ICO group than in the GLU group over time. Changes from baseline were more pronounced in the ICO group than in the GLU group for extracellular fluid volume (0.23 +/- 1.38 vs -1.0 +/- 1.48 L, p < 0.01) and blood pressure (systolic 1.5 +/- 24.0 vs -10.4 +/- 30.0 mmHg, p < 0.01; diastolic 1.5 +/- 13.5 vs -6.2 +/- 14.2 mmHg, p < 0.01). Compared to baseline, patients in the ICO group had better metabolic control than those in the GLU group: glucose absorption was more reduced (-17 +/- 44 vs -64 +/- 35 g/day) as were insulin needs (3.6 +/- 3.4 vs - 9.1 +/- 4.7 U/day, p < 0.01), fasting serum glucose (8.3 +/- 36.5 vs -37 +/- 25.8 mg/dL, p < 0.01), triglycerides (54.5 +/- 31.9 vs -54.7 +/- 39.9 mg/dL, p < 0.01), and glycated hemoglobin (0.79% +/- 0.79% vs -0.98% +/- 0.51%, p < 0.01). Patients in the ICO group had fewer adverse events related to fluid and glucose control than patients in the GLU group. CONCLUSION: Icodextrin represents a significant advantage in the management of high transport diabetic patients on PD, improving peritoneal UF and fluid control and reducing the burden of glucose overexposure, thereby facilitating metabolic control.

Aceptación del aprendizaje basado en problemas y de la evaluación entre pares por los estudiantes de medicina / Feasibility of implementing a learning based problem solving and peer evaluation approach among medical students in Mexico

Objetivo: Conocer el grado en el que los estudiantes aceptan y consideran útiles las técnicas de aprendizaje basado en problemas (ABP) y de evaluación entre pares. Analizar la asociación entre el número de casos clínicos de ABP revisados en el curso con la percepción de los estudiantes acerca de su aprendizaje, en un módulo de los ciclos básicos de la carrera de médico cirujano. Métodos: Se aplicó un cuestionario en forma anónima y voluntaria a 334 estudiantes de 12 grupos que cursaron un módulo predominantemente teórico del tercer ciclo de la carrera de médico cirujano en la Facultad de Estudios Superiores Iztacala, para evaluar su aceptación y percepción de la utilidad del ABP y de la evaluación entre pares, después de haber usado estas técnicas durante el curso semestral. La opinión sobre el grado de utilidad del ABP, la percepción del propio aprendizaje y el grado de aceptación de la noción de que las actividades de evaluación entre pares son justas y formativas se midieron mediante escalas ordinales tipo Likert; la asociación de estas variables con el número de casos clínicos revisados en el semestre se analizó mediante el coeficiente de correlación por rangos de Spearman. Resultados: La mayoría de los estudiantes consideró que el método de ABP es útil (82%) y que las actividades de evaluación entre pares son justas y formativas (70%). Los estudiantes que revisaron un número mayor de casos de ABP consideraron más útiles las actividades de ABP (rho = 0.489, p < 0.0001) y percibieron que habían tenido un mejor aprendizaje sobre inmunología (rho = 0.200, p < 0.0001). Conclusiones: Los resultados muestran una buena aceptación del método de ABP y de la evaluación entre pares por parte de los estudiantes. El número de casos de ABP revisados durante el semestre correlacionó con que se consideraran útiles las actividades de ABP y con la percepción de un mejor aprendizaje. Los resultados apoyan la aplicación de las técnicas de ABP y evaluación entre pares en cursos futuros.

OBJECTIVE: Assess the degree to which medical students accept and consider useful the techniques of problem based learning (PBL) and evaluation among peers. Analyze the association between the number of PBL clinical cases reviewed and the students' perception about their own learning in a basic course. METHODS: A questionnaire was administered to 334 students enrolled in the third semester of medical school (Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México). Questions included acceptability of PBL, peer evaluation, and their perception about the usefulness of these techniques after having used them during the school year. We used a Likert scale to measure opinions on the degree of usefulness of the PBL, perception of their own learning, and the acceptance of the notion that evaluation activities evaluation among peers promote justice and favor the student's character formation. We measured the association of these variables with the number of clinical cases studied using Spearman's rank correlation coefficient. RESULTS: Most of the students considered that PBL method is useful (82%) and that evaluation activities among peers promote justice and character formation (70%). Students who reviewed more PBL cases considered the PBL activities more useful (rho = 0.489, p < 0.0001), and perceived that they achieved a better learning experience (rho = 0.200, p < 0.0001). CONCLUSIONS: Results show a fair acceptance by the students of the PBL method and activities of peer evaluation. The number of clinical cases reviewed during the course correlated with considering the PBL to be a useful method and perceiving a better learning experience. Our results support the inclusion of PBL and peer evaluation in the medical school curricula.

[Staphylococcus aureus colonization and risk of developing a subsequent peritonitis episode caused by an identical strain, among pediatric patients admitted for continuous ambulatory peritoneal dialysis]. / Colonización por Staphylococcus aureus y riesgo de desarrollar episodio de peritonitis causado por cepa idéntica en pacientes pediátricos en diálisis peritoneal continua ambulatoria.

OBJECTIVE: To determine the risk of pediatric end stage renal disease patients undergoing continuous ambulatory peritoneal dialysis to develop a subsecuent peritonitis episode caused by an identical Staphylococcus aureus (SA) strain. METHODS: Longitudinal survey carried out in a CAPD center at the nephrology department of a tertiary care (reference) pediatric hospital. At recruitment, swabs were collected from the nares, exit site, and hands, respectively from 29 patients who were followed-up for a mean period of 369 +/- 80 days (range 224-516 days), and from the nares and hands of their mothers. Isolated SA strains were kept in BHI glycerol at -20 degrees C for subsequent analysis. Peritonitis episodes were monitored and registered. When a SA strain was isolated from the dialysate effluent it was compared with the preexisting strain by PFGE. RESULTS: We report 7 SA-mediated peritonitis episodes among 6 patients. Only one of these patients was a previous nasal carrier, and 2 were previous exit site carriers of the same SA strain. The relative risk of developing a peritonitis episode caused by a preexistent SA strain colonizing the exit site was 0.948. The relative risk of developing a peritonitis episode caused by a preexistent SA strain colonizing the nares was 0.525. CONCLUSIONS: SA carriers do not appear to be at higher risk of developing peritonitis by an SA related strain than non-carriers. Our results do not lend support to the recommendation of monitoring nasal or exit site carrier status in CAPD patients. The need of attempting to eradicate SA from nose or exit site is also questioned.

Colonización por Staphylococcus aureus y riesgo de desarrollar episodio de peritonitis causado por cepa idéntica en pacientes pediátricos en diálisis peritoneal continua ambulatoria / Staphylococcus aureus colonization and risk of developing a subsequent peritonitis episode caused by an identical strain, among pediatric patients admitted for continuous ambulatory peritoneal dialysis

Objetivo: Determinar el riesgo de los pacientes pediátricos con insuficiencia renal crónica terminal en programa de diálisis peritoneal continua ambulatoria (DPCA), portadores de Staphylococcus aureus (SA) en nariz, manos o sitio de salida del catéter, para desarrollar episodio de peritonitis causado por una cepa idéntica. Métodos: Estudio longitudinal en un centro de DPCA perteneciente a un hospital pediátrico de tercer nivel. Al ingresar al estudio se tomaron cultivos de las narinas, sitio de salida del catéter y manos, de 29 pacientes vigilados por un periodo promedio de 369 ± 80 días (de 224 a 516 días), y de las narinas y manos de sus madres. Las cepas de SA aisladas se conservaron en glicerol BHI a –20°C para análisis posterior. Los episodios de peritonitis se monitorearon y registraron. Cuando se aisló una cepa de SA del líquido de diálisis efluente se comparó con la previa identificada por electroforesis en gel de campos pulsados. Resultados: Se presentaron siete episodios de peritonitis causados por SA en seis pacientes, uno de los cuales era portador previo de la misma cepa en la nariz y dos en el sitio de salida del catéter. El riesgo relativo de desarrollar un episodio de peritonitis causado por una cepa preexistente localizada en el sitio de salida del catéter fue de 0.948, y de 0.525 por una cepa preexistente localizada en la nariz. Conclusiones: Los portadores de SA no parecen tener riesgo más alto de desarrollar peritonitis causada por una cepa de SA relacionada que los no portadores. No se sustenta la recomendación de monitorear el estado de portador nasal o en el sitio de salida del catéter en los pacientes tratados con DPCA. La conveniencia de erradicar el SA de la nariz o el sitio de salida del catéter también es cuestionable.

OBJECTIVE: To determine the risk of pediatric end stage renal disease patients undergoing continuous ambulatory peritoneal dialysis to develop a subsecuent peritonitis episode caused by an identical Staphylococcus aureus (SA) strain. METHODS: Longitudinal survey carried out in a CAPD center at the nephrology department of a tertiary care (reference) pediatric hospital. At recruitment, swabs were collected from the nares, exit site, and hands, respectively from 29 patients who were followed-up for a mean period of 369 +/- 80 days (range 224-516 days), and from the nares and hands of their mothers. Isolated SA strains were kept in BHI glycerol at -20 degrees C for subsequent analysis. Peritonitis episodes were monitored and registered. When a SA strain was isolated from the dialysate effluent it was compared with the preexisting strain by PFGE. RESULTS: We report 7 SA-mediated peritonitis episodes among 6 patients. Only one of these patients was a previous nasal carrier, and 2 were previous exit site carriers of the same SA strain. The relative risk of developing a peritonitis episode caused by a preexistent SA strain colonizing the exit site was 0.948. The relative risk of developing a peritonitis episode caused by a preexistent SA strain colonizing the nares was 0.525. CONCLUSIONS: SA carriers do not appear to be at higher risk of developing peritonitis by an SA related strain than non-carriers. Our results do not lend support to the recommendation of monitoring nasal or exit site carrier status in CAPD patients. The need of attempting to eradicate SA from nose or exit site is also questioned.

Predictive value of brain natriuretic peptides in patients on peritoneal dialysis: results from the ADEMEX trial.

BACKGROUND AND OBJECTIVES: Natriuretic peptides have been suggested to be of value in risk stratification in dialysis patients. Data in patients on peritoneal dialysis remain limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients of the ADEMEX trial (ADEquacy of peritoneal dialysis in MEXico) were randomized to a control group [standard 4 x 2L continuous ambulatory peritoneal dialysis (CAPD); n = 484] and an intervention group (CAPD with a target creatinine clearance > or =60 L/wk/1.73 m(2); n = 481). Natriuretic peptides were measured at baseline and correlated with other parameters as well as evaluated for effects on patient outcomes. RESULTS: Control group and intervention group were comparable at baseline with respect to all measured parameters. Baseline values of natriuretic peptides were elevated and correlated significantly with levels of residual renal function but not with body size or diabetes. Baseline values of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) but not proANP(1-30), proANP(31-67), or proANP(1-98) were independently highly predictive of overall survival and cardiovascular mortality. Volume removal was also significantly correlated with patient survival. CONCLUSIONS: NT-proBNP have a significant predictive value for survival of CAPD patients and may be of value in guiding risk stratification and potentially targeted therapeutic interventions.

Chronic kidney disease and dialysis in Mexico.

The increasing rates in incidence and prevalence of chronic kidney disease (CKD) are important challenges for health systems around the world, and are even more significant for undeveloped countries. In Mexico the prevalence of CKD seems to be similar to that in highly developed nations, with diabetes as the leading cause of CKD; however, human and economic resources seem to be insufficient for treatment needs. This is reflected in the unacceptably high mortality rates and in noncompliance with established standards and guidelines. Several measures need to be taken to improve this picture, such as more efficient programs for the prevention of obesity, diabetes, and hypertension. Organizing a national registry of patients with CKD is now a pressing need, as is a continuous search for additional funding and budgets to increase the number of qualified nephrologists and specialized nurses and to continue the much-needed research on CKD.

Drug treatment of hypertension: compliance and adverse reactions in a cohort of hypertensive patients in a primary care setting.

OBJECTIVES: The primary was to assess the frequency of therapeutic non-compliance due to ADRs in a cohort of patients with recently diagnosed systemic hypertension. The secondary objectives were to evaluate the blood pressure control during the follow-up in the whole cohort and in patients who received non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A cohort of 73 recently diagnosed ambulatory hypertensive patients was followed-up for 6 months. Validated questionnaires for identification of therapeutic scheme changes and ADRs were applied monthly, during each medical visit. RESULTS: Family physicians selected monotherapy in 79% of patients. The frequency of therapeutic non-compliance was 44%; non-compliance secondary to ADR was 7%. Systolic and diastolic blood pressure at the beginning of the study were 140 +/- 15/90 +/- 15 mm Hg for the whole cohort. At the end of the study the figures were 130 +/- 11/85 +/- 6 (p < 0.001). Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) had higher blood pressure levels than the groups of patients not receiving such kind of drugs (134 +/- 10 vs. 128 +/- 8 mm Hg, p = 0.025 and 88 +/- 7 vs. 83 +/- 5 mm Hg, p = 0.05). CONCLUSIONS: The drugs used in the present study as monotherapy are considered acceptable choices for hypertension treatment. The frequency of therapeutic non-compliance was within the limits reported in the literature and the frequency of therapeutic non-compliance secondary to ADRs in this cohort was lower than that reported in the literature. Higher blood pressure was found in the group of patients receiving NSAIDs.

Drug treatment of hypertension: compliance and adverse reactions in a cohort of hypertensive patients in a primary care setting / Tratamiento farmacológico antihipertensivo: Cumplimiento y reacciones adversas en una cohorte de pacientes hipertensos en atención primaria

Objectives. The primary was to assess the frequency of therapeutic non-compliance due to ADRs in a cohort of patients with recently diagnosed systemic hypertension. The secondary objectives were to evaluate the blood pressure control during the follow-up in the whole cohort and in patients who received non-steroidal anti-inflammatory drugs (NSAIDs). Methods. A cohort of 73 recently diagnosed ambulatory hypertensive patients was followed-up for 6 months. Validated questionnaires for identification of therapeutic scheme changes and ADRs were applied monthly, during each medical visit. Results. Family physicians selected monotherapy in 79% of patients. The frequency of therapeutic non-compliance was 44%; non-compliance secondary to ADR was 7%. Systolic and diastolic blood pressure at the beginning of the study were 140 ± 15/90 ± 15 mm Hg for the whole cohort. At the end of the study the figures were 130 ± 11/85 ± 6 (p < 0.001). Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) had higher blood pressure levels than the groups of patients not receiving such kind of drugs (134 ± 10 vs. 128 ± 8 mm Hg, p = 0.025 and 88 ± 7 vs. 83 ± 5 mm Hg, p = 0.05). Conclusions. The drugs used in the present study as monotherapy are considered acceptable choices for hypertension treatment. The frequency of therapeutic non-compliance was within the limits reported in the literature and the frequency of therapeutic non-compliance secondary to ADRs in this cohort was lower than that reported in the literature. Higher blood pressure was found in the group of patients receiving NSAIDs.

Objetivos. El objetivo primario fue evaluar la frecuencia de falta de cumplimiento terapéutico debido a la presencia de reacciones adversas a medicamentos (RAMs) con el uso de antihipertensivos; los objetivos secundarios fueron evaluar el control de la presión arterial durante el seguimiento y en aquellos pacientes que recibieron fármacos antiinflamatorios no esteroideos. Métodos. Se integró una cohorte de 73 pacientes hipertensos de reciente diagnóstico, a los que se les vigiló durante seis meses. En cada visita médica mensual se les aplicaron cuestionarios validados, para identificar cambios en el esquema terapéutico y RAMs. Resultados. Los médicos familiares emplearon monoterapia en 79% de los pacientes. La falta de cumplimiento terapéutico se presentó en 44%; el incumplimiento terapéutico secundario a RAMs se observó en 7% de los casos. En todos los pacientes la presión arterial sistólica y diastólica al inicio del estudio fue 140 ± 15/90 ± 15 mm Hg y al final del estudio las cifras fueron 130 ± 11 / 85 ± 6 (p < 0.001). Los pacientes que recibieron fármacos antiinflamatorios no esteroideos (AINEs) tuvieron cifras de presión arterial más elevadas que pacientes que no recibieron este tipo de fármacos (134 ± 10 vs. 128 ± 8, p = 0.025 y 88 ±7 vs. 83 ± 5 mm Hg, p - 0.05). Conclusiones. Los fármacos empleados en este estudio como monoterapia son fármacos aceptados para el tratamiento de la hipertensión. La frecuencia de falta de cumplimiento terapéutico se ubicó dentro de los límites descritos en la literatura y la falta de cumplimiento terapéutico secundario a RAMs fue menor que lo informado en la literatura. Se observaron cifras de presión arterial elevadas en pacientes que recibieron AINEs.

Conjugated estrogens and tibolone modify the gonadotrophin glycosylation pattern in postmenopausal women.

OBJECTIVE: The purpose of this study was to evaluate the changes in the percentage of glycosylation of FSH and LH when using conjugated estrogens and tibolone as hormonal therapy (HT) in postmenopausal compared with regular menstrual cycles. DESIGN: The study had three groups, with 10 participants in each group. The control group consisted of 10 women with normal menstrual cycles, a second group with 10 postmenopausal patients who received conjugated estrogens (Premarin 0.625 mg), and a third group had 10 patients who received tibolone (Livial 2.5 mg). All patients had hormonal determinations before and 6 months after the use of HT. Concavalin-A was used to separate the different glycosylated species of gonadotrophins, defined as unbound (UB: triantennary and bisecting oligosaccharides), weakly bound (WB: biantennary and truncated oligosaccharides), and firmly bound isoforms (FB: hybrid- and high-mannose-type oligosaccharides) in patients serum. Elusions containing the fractions with the isoforms were concentrated using Centriprep membranes (Amicon, Beverly, Mass., USA) and the different gonadotrophins isoforms were quantified by chemiluminescence using an automated system Immulite. RESULTS: The pattern of distribution of gonadotrophins glycosylation in patients treated with conjugated estrogens and tibolone was similar to that observed in the control group with normal menstrual cycles, although with different glycosylation percentage. When the glycosylation percentages were compared for FSH, in the fraction UB the glycosylation did not have significant differences, but the fraction WB that has isoforms with high amounts of oligosaccharides showed a different percentage of glycosylation, where the recovery percentage was bigger with tibolone use (p < 0.05). The FB fraction had similar hormonal glycosylation with estrogens and tibolone use. When compared, LH glycosylation showed significant differences (p < 0.05) in the fraction UB with a bigger glycosylation degree, and in the fraction FB with a smaller glycosylation percentage, both in the tibolone group compared with conjugated estrogens use. CONCLUSIONS: Our results show that there are different percentages of glycosylation of gonadotrophins depending on type of HT (conjugated estrogens vs tibolone), and this could be of utility in young women with ovarian problem since to know the isoform that more favors to cellular activity could help a better therapeutic.

Inflammation and oxidative stress markers by pentoxifylline treatment in rats with chronic renal failure and high sodium intake.

BACKGROUND: Inflammation is a risk factor for mortality in patients with chronic renal failure (CRF). Prevention of extracellular fluid volume expansion and the use of certain drugs such as pentoxifylline (PF) may reduce inflammation and oxidative stress. The aim of this study is to analyze the effect of dietary sodium and PF treatment on the levels of inflammation and oxidative stress markers in rats with CRF. METHODS: CRF was induced in rats by 5/6 nephrectomy. Different groups of rats with CRF received low sodium (LNa, 0.01% sodium chloride [NaCl] in the diet), normal sodium (NNa, 0.05% NaCl in the diet), or high sodium diet (HNa, as in NNa plus 0.015% NaCl in the drinking water). An additional group received HNa plus PF treatment (25 mg/kg in the drinking water) for 60 days. Circulating creatinine, tumor necrosis factor alpha (TNF-alpha), nitrites, thiols, malondialdehyde (MDA), and advanced oxidation protein products (AOPP) were measured. RESULTS: Higher sodium intake was associated with higher serum creatinine levels (median; interquartile range), LNa, 1.255; 0.715, NNa, 1.305; 0.495, HNa, 2.015; 1.115 mg/dL (p < 0.05), TNF-alpha levels, LNa, 2.7; 23.6, NNa, 36.7; 47.7, HNa, 263.7; 126.5 pg/mL, and AOPP, LNa, 31.72; 7.55, NNa, 45.89; 9.38, HNa, 60.41; 37.42 microg/mL. MDA was not modified by sodium intake. PF treatment decreased serum TNF-alpha (151.7 pg/mL, p < 0.5) and AOPP (49.83 micromol/L, p < 0.03), and increased nitrites and thiols levels when compared with HNa rats. CONCLUSIONS: High sodium intake increases the serum concentration of inflammation and oxidative stress markers; these changes are prevented by PF treatment.

Inflammation and extracellular volume expansion are related to sodium and water removal in patients on peritoneal dialysis.

BACKGROUND: Inflammation is an important risk for mortality in dialysis patients. Extracellular fluid volume (ECFv) expansion, a condition commonly seen in peritoneal dialysis (PD) patients, may be associated with inflammation. However, published support for this relationship is scarce. OBJECTIVES: To quantify the proportion of patients on PD with inflammation and to analyze the role of ECFv expansion and the factors related to these conditions. DESIGN: A prospective, multicenter cross-sectional study in six hospitals with a PD program. PATIENTS AND METHODS: Adult patients on PD were studied. Clinical data, body composition, and sodium and fluid intake were recorded. Biochemical analysis, C-reactive protein (CRP), and peritoneal and urinary fluid and sodium removal were also measured. RESULTS: CRP values positive (>or=3.0 mg/L) for inflammation were found in 147 (80.3%) and negative in 36 patients. Patients with positive CRP had higher ECFv/total body water (TBW) ratio (women 47.69 +/- 0.69 vs 47.36 +/- 0.65, men 43.15 +/- 1.14 vs 42.84 +/- 0.65; p < 0.05), higher serum glucose (125.09 +/- 81.90 vs 103.28 +/- 43.30 mg/dL, p < 0.03), and lower serum albumin (2.86 +/- 0.54 vs 3.17 +/- 0.38 g/dL, p < 0.001) levels. They also had lower ultrafiltration (1003 +/- 645 vs 1323 +/- 413 mL/day, p < 0.005) and total fluid removal (1260 +/- 648 vs 1648 +/- 496 mL/day, p < 0.001), and less peritoneal (15.59 +/- 162.14 vs 78.11 +/- 110.70 mEq/day, p < 0.01) and total sodium removal (42.06 +/- 142.49 vs 118.60 +/- 69.73 mEq/day, p < 0.001). In the multivariate analysis, only ECFv/TBW was significantly (p < 0.04) and independently associated with inflammation. ECFv/TBW was correlated with fluid removal (r = 0.16, p < 0.03) and renal sodium removal (r = 0.2, p < 0.01). CONCLUSION: The data suggest that ECFv expansion may have a significant role as an inflammatory stimulus. The results disclose a relationship between the two variables, ECFv expansion and inflammation, identified as independent risk factors for mortality in PD patients.