Facilitation by serum albumin of renal tubular secretion of organic anions.

The role of albumin in tubular secretion of the organic anions p-aminohippurate (PAH, 21% albumin-bound at 1 microM) and methotrexate (MTX, 55% bound at 1 microM), and of the organic cation N1-methylnicotinamide (NMN, not bound), was investigated in isolated rabbit S2 proximal tubules. PAH or MTX secretory rates were low in the absence of colloids or in the presence of 1 g/dl dextran 40, and were reversibly two- to sevenfold stimulated by either 1 g/dl bovine (BSA, either regular, defatted, and/or dialyzed) or rabbit serum albumin, or by dialyzed native rabbit plasma. NMN secretion was not stimulated by either dextran or albumin. Luminal BSA had no effect, but stimulation of PAH secretion was observed when albumin was present in both lumen and bath. This secretion was BSA concentration-dependent up to a 1 g/dl BSA. Saturation experiments suggested that 1 g/dl BSA may increase PAH apparent affinity for secretion, with no change in its maximum velocity. Albumin appears therefore to facilitate organic anion proximal secretion by an effect unrelated to oncotic pressure or to the extent of organic anion binding.

Development of the first disease activity index for eosinophilic esophagitis: update on the EEsAI in 2012

Background and Aims: The international E EsAI s tudy g roup is currently d eveloping the first activity index ( EEsAI) specific for E osinophilic Esophagitis (EoE). G oal: T o develop, e valuate and validate the EEsAI. Methods: T he development c omprises three p hases: 1. Selection of c andidate items ( completed); 2. Evaluation of t he activity index i n a first patient cohort (in progress, p atient recruitment completed); and 3. Validation in a s econd EoE patient cohort. F ocus group interviews with patients were used in p hase 1 to g enerate patient r eported outcomes (PRO) according to g uidelines o f regulatory authorities (FDA a nd EMA), whereas the section of biologic items was developed by Delphi rounds o f international E oE experts from E urope and North America. Results: T he EEsAI has a modular c omposition to a ssess the following components o f EoE activity: p atient r eported outcomes, e ndoscopic activity, histologic activity, laboratory activity, a nd quality of l ife (QoL). Definitions for a ll aspects o f endoscopic and histologic appearance were e stablished by consensus r ounds a mong E oE experts. S ymptom a ssessment tools were c reated that t ake into account d ifferent food consistencies as w ell as f ood avoidance and specific processing strategies. The EEsAI i s currently e valuated in a cohort of a dult EoE patients since M arch 2 011 (patient recruitment completed). Conclusions: The EEsAI standardizes outcome assessment in EoE t rials. T he collaboration with i nternational E oE e xperts a s well as f ollowing o f the guidelines f rom regulatory authorities will lead to its wide applicability.

Troubles du sommeil chez des patients présentant une insuffisance rénale chronique [Sleep disorders in patients with chronic renal insufficiency].

Sleep disorders, especially insomnia, daytime sleepiness, sleep apnea syndrome and restless legs syndrome are very frequently encountered in patients with chronic renal failure whether or not they undergo renal replacement therapy. The causes of sleep disorders are multifactorial and not only linked to the renal disease itself, but also to its treatment and its associated psychosocial factors. This article discusses the prevalence and physiopathology of the most frequently encountered sleep disorders in chronic renal failure patients, and highlights the actually available therapeutic options.

Reliability and validity of the cross-culturally adapted French version of the Core Outcome Measures Index (COMI) in patients with low back pain.

PURPOSE: To conduct a cross-cultural adaptation of the Core Outcome Measures Index (COMI) into French according to established guidelines. METHODS: Seventy outpatients with chronic low back pain were recruited from six spine centres in Switzerland and France. They completed the newly translated COMI, and the Roland Morris disability (RMQ), Dallas Pain (DPQ), adjectival pain rating scale, WHO Quality of Life, and EuroQoL-5D questionnaires. After ~14 days RMQ and COMI were completed again to assess reproducibility; a transition question (7-point Likert scale; "very much worse" through "no change" to "very much better") indicated any change in status since the first questionnaire. RESULTS: COMI whole scores displayed no floor effects and just 1.5% ceiling effects. The scores for the individual COMI items correlated with their corresponding full-length reference questionnaire with varying strengths of correlation (0.33-0.84, P < 0.05). COMI whole scores showed a very good correlation with the "multidimensional" DPQ global score (Rho = 0.71). 55 patients (79%) returned a second questionnaire with no/minimal change in their back status. The reproducibility of individual COMI 5-point items was good, with test-retest differences within one grade ranging from 89% for 'social/work disability' to 98% for 'symptom-specific well-being'. The intraclass correlation coefficient for the COMI whole score was 0.85 (95% CI 0.76-0.91). CONCLUSIONS: In conclusion, the French version of this short, multidimensional questionnaire showed good psychometric properties, comparable to those reported for German and Spanish versions. The French COMI represents a valuable tool for future multicentre clinical studies and surgical registries (e.g. SSE Spine Tango) in French-speaking countries.

Coping religioso/espiritual em pessoas com doença renal crônica em tratamento hemodialítico

O estudo tem como objetivo investigar o uso do coping religioso/espiritual em pacientes com doença renal crônica em hemodiálise. A investigação ocorreu em uma clínica de hemodiálise, por meio de entrevista utilizando um questionário sociodemográfico e a escala de coping religioso/espiritual. Para análise dos dados, foram empregados a estatística descritiva e o teste coeficiente de correlação de Sperman, a análise de variância e o modelo de regressão linear múltipla. Foram entrevistados 123 indivíduos, dos quais 79,6% apresentaram escore alto para o coping religioso/espiritual e nenhum deles apresentou os escores baixos e irrisórios. As variáveis que influenciaram no comportamento do coping religioso/espiritual foram: sexo, faixa etária, tempo de tratamento, renda familiar e prática religiosa. Conclui-se que os pacientes em estudo utilizam de modo positivo o coping religioso/espiritual como estratégia de enfrentamento da doença, destacando-se as mulheres, com renda familiar maior e que frequentam semanalmente a igreja.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

A sepse como causa de lesão renal aguda: modelo experimental

A sepse associada à falência de múltiplos órgãos como a lesão renal aguda (LRA) demonstra alta taxa de mortalidade no paciente crítico. Este estudo investigou a LRA induzida pela sepse em modelo experimental. Foram utilizados ratos da raça Wistar, adultos e machos divididos nos seguintes grupos: Controle - controle cirúrgico e Sepse - indução da sepse pela ligadura e punção do cécon (LPC). Foram avaliados os parâmetros fisiológicos (temperatura retal, pressão arterial média - PAM, glicemia sérica e fluxo urinário); a função renal (clearance de creatinina); o estresse oxidativo (peróxidos urinários e substâncias reativas com ácido tiobarbitúrico - TBARS) e realizada a análise histológica renal. O estudo conclui que a LRA induzida pela sepse caracteriza-se por lesão endotelial com disfunção hemodinâmica, liberação de mediadores inflamatórios e geração de espécies reativas de oxigênio (EROs) por células tubulares, caracterizando-se como uma associação de vasoconstrição renal de origem hemodinâmica e inflamatória.

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2±6.6 fmol/mL (mean±SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14±3) and submaxillary gland (521±315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89±9) was not different from right renal BK (75±23). Similarly, KA was comparable in the two kidneys (left 18.0±1.5, right 15.8±1.4μkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.

Panel index VAR models: Specification, Estimation, Testing and Leading Indicators

This paper proposes a method to conduct inference in panel VAR models with cross unit interdependencies and time variations in the coefficients. The approach can be used to obtain multi-unit forecasts and leading indicators and to conduct policy analysis in a multiunit setups. The framework of analysis is Bayesian and MCMC methods are used to estimate the posterior distribution of the features of interest. The model is reparametrized to resemble an observable index model and specification searches are discussed. As an example, we construct leading indicators for inflation and GDP growth in the Euro area using G-7 information.

Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study).

Marijuana use has been associated with increased appetite, high caloric diet, acute increase in blood pressure, and decreases in high-density lipoprotein cholesterol and triglycerides. Marijuana is the most commonly used illicit drug in the United States, but its long-term effects on body mass index (BMI) and cardiovascular risk factors are unknown. Using 15 years of longitudinal data from 3,617 black and white young adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors. Of the 3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was associated with male gender, tobacco smoking, and other illicit drug use. More extensive marijuana use was associated with a higher caloric intake (2,746 kcal/day in never users to 3,365 kcal/day in those who used marijuana for > or = 1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl or 0.95 to 1.13 mmol/L, all p values for trend < 0.001), but not with higher BMI and lipid and glucose levels. In multivariate analysis, the associations between marijuana use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in marijuana users. In conclusion, although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.

Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Development and validation of the Family Vulnerability Index to Disability and Dependence (FVI-DD)

This exploratory, descriptive, cross-sectional, and quantitative study aimed to develop and validate an index of family vulnerability to disability and dependence (FVI-DD). This study was adapted from the Family Development Index, with the addition of social and health indicators of disability and dependence. The instrument was applied to 248 families in the city of Sao Paulo, followed by exploratory factor analysis. Factor validation was performed using the concurrent and discriminant validity of the Lawton scale and Katz Index. The descriptive level adopted for the study was p < 0.05. The final vulnerability index comprised 50 questions classified into seven factors contemplating social and health dimensions, and this index exhibited good internal consistency (Cronbach’s alpha = 0.82). FVI-DD was validated using both the Lawton scale and Katz Index. We conclude that FVI-DD can accurately and reliably assess family vulnerability to disability and dependence.

Ankle-Brachial Index: Nurses Strategy To Cardiovascular Disease Risk Factors Identification

Elevated risk of fatal and non-fatal cardiovascular events is associated with high prevalence of peripheral arterial disease, with assessment through the ankle-brachial index (ABI). This study aimed to demonstrate that the ABI and the Edinburgh Claudication Questionnaire are tools to be used by nurses in prevention and/or treatment of CVD (cardiovascular disease). A cross-sectional study was carried out with patients from a cardiovascular clinic. The Edinburgh Claudication Questionnaire was applied and the ABI was measured with the formula (ABI= Blood Pressure Ankle/Blood Pressure Brachial). A total of 115 patients were included, most were females (57.4%), aged 60.6 ± 12.5 years. The most prevalent risk factors were hypertension (64.3%), physical inactivity (48.7%) and family history (58.3%). The study showed that abnormal ABI was frequently found and 42.6% of the patients with abnormal ABI showed intermittent claudication. The method to evaluate the ABI associated to the Edinburg Claudication Questionnaire, can be easily used by nurses in the clinical evaluation of asymptomatic and symptomatic CVD patients.

Gastric outlet obstruction by Brunner's gland hyperplasia in an 8-year-old child.

Several cases of Brunner's gland hyperplasia causing hemorrhage, obstruction, or intussusception have been published in the adult literature. Similar cases in the pediatric population are very rare and have only been described twice, always associated with chronic renal failure. We report the third and youngest case of gastric outlet obstruction because of Brunner's gland hyperplasia focusing on histopathologic condition and treatment based on a review of the literature.