Validation of US CDC National Death Index mortality data, focusing on differences in race and ethnicity.

OBJECTIVES: The US Center for Disease Control and Prevention's National Death Index (NDI) is a gold standard for mortality data, yet matching patients to the database depends on accurate and available key identifiers. Our objective was to evaluate NDI data for future healthcare research studies with mortality outcomes. METHODS: We used a Kaiser Permanente Mid-Atlantic States' Virtual Data Warehouse (KPMAS-VDW) sourced from the Social Security Administration and electronic health records on members enrolled between 1 January 2005 to 31 December 2017. We submitted data to NDI on 1 036 449 members. We compared results from the NDI best match algorithm to the KPMAS-VDW for vital status and death date. We compared probabilistic scores by sex and race and ethnicity. RESULTS: NDI returned 372 865 (36%) unique possible matches, 663 061 (64%) records not matched to the NDI database and 522 (<1%) rejected records. The NDI algorithm resulted in 38 862 records, presumed dead, with a lower percentage of women, and Asian/Pacific Islander and Hispanic people than presumed alive. There were 27 306 presumed dead members whose death dates matched exactly between the NDI results and VDW, but 1539 did not have an exact match. There were 10 017 additional deaths from NDI results that were not present in the VDW death data. CONCLUSIONS: NDI data can substantially improve the overall capture of deaths. However, further quality control measures were needed to ensure the accuracy of the NDI best match algorithm.

State of ex situ conservation of landrace groups of 25 major crops.

Crop landraces have unique local agroecological and societal functions and offer important genetic resources for plant breeding. Recognition of the value of landrace diversity and concern about its erosion on farms have led to sustained efforts to establish ex situ collections worldwide. The degree to which these efforts have succeeded in conserving landraces has not been comprehensively assessed. Here we modelled the potential distributions of eco-geographically distinguishable groups of landraces of 25 cereal, pulse and starchy root/tuber/fruit crops within their geographic regions of diversity. We then analysed the extent to which these landrace groups are represented in genebank collections, using geographic and ecological coverage metrics as a proxy for genetic diversity. We find that ex situ conservation of landrace groups is currently moderately comprehensive on average, with substantial variation among crops; a mean of 63% ± 12.6% of distributions is currently represented in genebanks. Breadfruit, bananas and plantains, lentils, common beans, chickpeas, barley and bread wheat landrace groups are among the most fully represented, whereas the largest conservation gaps persist for pearl millet, yams, finger millet, groundnut, potatoes and peas. Geographic regions prioritized for further collection of landrace groups for ex situ conservation include South Asia, the Mediterranean and West Asia, Mesoamerica, sub-Saharan Africa, the Andean mountains of South America and Central to East Asia. With further progress to fill these gaps, a high degree of representation of landrace group diversity in genebanks is feasible globally, thus fulfilling international targets for their ex situ conservation.

A Mixed Methods Study Describing the Quality of Healthcare Received by Transgender and Gender Nonconforming Patients at a Large Integrated Health System.

Transgender and gender nonconforming (TGNC) patients have been seeking medical care in higher numbers and have faced unique social, personal, and health issues that affect the quality of care they receive. The purpose of this study was to conduct a mixed-methods study to describe TGNC care at Kaiser Permanente Mid-Atlantic States, a large integrated health system. We used a transgender registry to describe a TGNC patient population and compared healthcare utilization between TGNC patients and non-TGNC patients. Four focus groups were also conducted among 28 patients. Atlas.ti software was used to code and analyze themes for the qualitative analysis. Among the 282 adults TGNC patients, the mean age was 32.6 years. Of the study sample, 59% were White, and 27% were Black. TGNC patients demonstrated an increased use of email/telephone visits and the online patient portal and more cancellations and no-shows compared to non-TGNC controls. Of the 28 TGNC patients who participated in the focus groups, 39% identified as female, 21% as a transman, and 18% as non-binary/genderqueer. Participants were predominantly White (68%), highly educated (74%), and reported use of hormones (89%). Themes that emerged from our qualitative analysis included: limited availability of TGNC information; positive and negative sentiments regarding patient-provider interactions; issues with case management; limited access to care; lack of coordination of care; negative staff experiences. We identified specific areas in a health system to improve the quality of care of TGNC patients, including specific TGNC training for providers and staff, a source of TGNC information/resources, and hiring and training TGNC-specific case managers.

Factors contributing to racial disparities in influenza vaccinations.

BACKGROUND: Racial/ethnic disparities in rates of influenza vaccinations in the US remain an issue even among those with access, no out-of-pocket costs, and after adjusting for confounders. We used an approach called the Oaxaca-Blinder (OB) decomposition method to ascertain the contribution of covariates individually and in aggregate to the racial disparity in influenza vaccination. METHODS: We included members > = 18 years of age as of 05/01/2014 with continuous enrollment through 04/30/2015. Influenza vaccination was defined by diagnosis, procedure, or medication codes, or documentation in the immunization table. Characteristics were reported by race. Logistic regression models estimated the odds of vaccination associated with: (1) race; and (2) covariates stratified by race. The Oaxaca-Blinder (OB) method calculated the contribution of covariates to the difference or disparity in vaccination between Blacks and Whites. RESULTS: We found that among adults, 44% were vaccinated; 55% were Black; and 45% were White. Black members have 42% lower odds of vaccination than White members. The contribution of the differences in the average value of the study covariates between Black and White members (the OB covariate effect) accounted for 29% of the racial disparity. The contributions to the total White-Black disparity in vaccination included: age (16%), neighborhood median income (11%), and registration on the online patient portal (13%). The contribution of the differences in how the covariates impact vaccination (OB coefficient effect) accounted for 71% of the disparity in vaccination between Blacks and Whites. CONCLUSION: In conclusion, equalizing average covariate values in Blacks and Whites could reduce the racial disparity in influenza vaccination by 29%. For health system vaccine campaigns, improving registration on the patient portal may be a target component of an effective system-level strategy to reduce racial disparities in vaccination. Additional information on patient-centered factors could further improve the value of the OB approach.

Fetal myocardial performance index in assessment and management of small-for-gestational-age fetus: a cohort and nested case-control study.

OBJECTIVE: To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small-for-gestational-age (SGA) fetus/growth-restricted fetus (FGR). METHODS: This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24-38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age-matched controls, and assessed the correlation with perinatal outcome and other Doppler measures. RESULTS: Fifty-two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age-matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta-MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3rd vs 3rd -10th centile; early- vs late-onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3rd vs 3rd -10th centile comparison. CONCLUSIONS: MPI did not demonstrate clinical utility in either triage or longitudinal follow-up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single-center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Beat-to-beat variability of fetal myocardial performance index.

OBJECTIVES: To determine whether there is beat-to-beat (BTB) variability in the fetal left myocardial performance index (MPI), as evaluated by an automated system, and whether there is a correlation between MPI and fetal heart rate (FHR). METHODS: This was a prospective cross-sectional study of uncomplicated, morphologically normal, singleton pregnancies at 20-38 weeks' gestation. Multiple cineloops for left MPI measurement were acquired during a single examination of each fetus. Raw cineloop data were analyzed by our automated MPI system (intraclass correlation coefficient of 1.0 for any given waveform) to produce a set of MPIs. The corresponding instantaneous FHR was measured for each individual cardiac cycle for which MPI was calculated. RESULTS: Data from 29 fetuses were analyzed; mean MPI was 0.52, mean FHR was 150 beats per min and the median number of cardiac cycles examined per fetus was 70 (interquartile range, 31-115). Marked BTB variability was noted; median coefficient of variation was 10% (range, 5.5-13.9%). FHR was weakly correlated with absolute MPI (r = 0.22; P < 0.05). BTB variation in MPI as a percentage of the mean MPI was not significantly correlated with FHR (r = 0.031; P = 0.146). When standard error of the mean of all MPI values was divided by the mean for each case, it showed that at least four cardiac cycles should be averaged to reduce MPI variability to approximately ± 5%. CONCLUSION: There is significant BTB variability in fetal left MPI, which has an overall weak correlation with FHR. This could be a factor affecting the consistency of MPI values reported by different research groups. Variability would be reduced by averaging 4-5 cardiac cycles per fetus. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Laparoscopic management of a fallopian tubal torsion complicated by a large hydrosalpinx.

Clinical presentation of an adnexal mass is often non-specific and may mimic a range of gynecological pathology, as well as renal or gastrointestinal causes of lower abdominal pain. While a common entity, its association with a fallopian tube pathology is very uncommon. Imaging such as ultrasound has been diagnostic in the evaluation of a pelvic mass, and has been reported as assisting the diagnosis of fallopian tubal torsion. A pelvic mass of cystic nature can be removed by cystectomy, while treatment options for a torted fallopian tube include surgical detorsion if detected early, or a salpingectomy should there be evidence of necrosis. We report a rare case of fallopian tube torsion complicated by a large hydrosalpinx which was managed by laparoscopic surgery.

Renal clearance of B-type natriuretic peptide and amino terminal pro-B-type natriuretic peptide a mechanistic study in hypertensive subjects.

OBJECTIVES: This study sought to compare the renal clearance mechanisms of B-type natriuretic peptide (BNP) and amino terminal pro-B-type natriuretic peptide (NT-proBNP). BACKGROUND: The small molecular weight proteins (SMWPs) BNP and NT-proBNP both inversely correlate with glomerular filtration rate (GFR). Whether this association is causal or confounding is unknown and has been the basis of widespread speculation. METHODS: We combined measurements of BNP and NT-proBNP concentrations in the renal arteries and veins of 165 subjects undergoing renal arteriography with invasive renal plasma flow (RPF) measurements and echocardiography. Fractional extraction (FE) of BNP and NT-proBNP was computed. RESULTS: The BNP and NT-proBNP concentrations correlated similarly to GFR (r = -0.35 and r = -0.30, respectively; p < 0.001 for both) but the NT-proBNP/BNP serum ratio was negatively associated with GFR (r = -0.21, p = 0.008). Median FE(BNP) was 0.21 (interquartile range [IQR] 0.16 to 0.22) for left and 0.22 (IQR 0.17 to 0.29) for right kidneys. Median FE(NT-proBNP) was 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FE(BNP) correlated with GFR (left: r = 0.26, p = 0.008; right: r = 0.21, p = 0.03) as did FE(NT-proBNP) (left: r = 0.25, p = 0.005; right: r = 0.20, p = 0.02). Although FE(BNP) and FE(NT-proBNP) correlated strongly with each other (left: r = 0.66; right: r = 0.60; p < 0.001 for both), left and right FE(NT-proBNP/BNP) ratios were not influenced by GFR (r = 0.10, p = 0.30 and r = 0.08, p = 0.43, respectively). Multivariate analyses confirmed that FE was not independently associated with BNP or NT-proBNP concentrations. CONCLUSIONS: Contrary to widespread belief (but in line with the renal physiology of SMWP), BNP and NT-proBNP are equally dependent on renal function for their clearance.

Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) dimerizes with retinoid X receptor (RXR) and regulates the transcription of genes encoding xenobiotic-metabolizing enzymes such as CYP3A4. Rifampin, the classical activator of CYP3A4, binds to SXR directly. It is unclear whether various natural and synthetic retinoids can regulate the expression of CYP3A4. To evaluate the effects of retinoids on the RXR/SXR-mediated pathway, transient transfection assays were performed on both CV-1 and human hepatoma Huh7 cells using a reporter construct containing multiple RXR/SXR consensus binding elements (an everted repeat with a 6-nucleotide spacer, ER-6). The results revealed that eight out of 13 retinoids screened significantly induced the RXR/SXR-mediated pathway in Huh7 cells. At an equal molar concentration, the acid forms (9-cis-RA, 13-cis-RA, and all-trans-RA) or aldehyde, the direct precursor of acid (9-cis-retinal and 13-cis-retinal), exhibited a greater or similar potency than rifampin. Depending on the ligands, RXR may serve as a silent or an active partner of SXR. Additionally, retinoids can increase CYP3A4 enzyme activity in Huh7 cells. To further evaluate the potential drug-drug interactions, which may be caused by retinoids, Huh7 cells were pretreated with 9-cis-RA and followed by acetaminophen. We showed that 9-cis-RA enhanced the covalent binding of N-acetyl-p-quinoneimine, a toxic intermediate of acetaminophen produced by phase I enzymes oxidation. This result suggested that drug-drug interaction might occur between 9-cis-RA and acetaminophen in human liver cells. Taken together, retinoids activate the RXR/SXR-mediated pathway and regulate the expression of CYP3A4. Thus, retinoids potentially can cause drug-drug interactions when they are administered with other CYP3A4 substrates.

Retinoid X receptor alpha Regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver.

Nuclear receptors, including constitutive androstane receptor, pregnane X receptor, and retinoid X receptor (RXR), modulate acetaminophen (APAP)-induced hepatotoxicity by regulating the expression of phase I cytochrome P450 (P450) genes. It has not been fully resolved, however, whether they regulate APAP detoxification at the phase II level. The aim of the current study was to evaluate the role of RXRalpha in phase II enzyme-mediated detoxification of APAP. Wild-type and hepatocyte-specific RXRalpha knockout mice were treated with a toxic dose of APAP (500 mg/kg i.p.). Mutant mice were protected from APAP-induced hepatotoxicity, even though basal liver glutathione (GSH) levels were significantly lower in mutant mice compared with those of wild-type mice. High-performance liquid chromatography analysis of APAP metabolites revealed significantly greater levels of APAP-GSH conjugates in livers and bile of mutant mice compared with those of wild-type mice. Furthermore, hepatocyte RXRalpha deficiency altered the gene expression profile of the glutathione S-transferase (Gst) family. Basal expression of 13 of 15 Gst genes studied was altered in hepatocyte-specific RXRalpha-deficient mice. This probably led to enhanced APAP-GSH conjugation and reduced accumulation of N-acetyl-p-benzoquinone imine, a toxic electrophile that is produced by biotransformation of APAP by phase I P450 enzymes. In conclusion, the data presented in this study define an RXRalpha-Gst regulatory network that controls APAP-GSH conjugation. This report reveals a potential novel strategy to enhance the detoxification of APAP or other xenobiotics by manipulating Gst activity through RXRalpha-mediated pathways.

Ten years of breast screening in the Nova Scotia Breast Screening Program, 1991-2001. experience: use of an adaptable stereotactic device in the diagnosis of screening-detected abnormalities.

OBJECTIVE: To evaluate and present 10-year outcomes of the Nova Scotia Breast Screening Program (NSBSP), a population-based screening program in the province of Nova Scotia, Canada, total population 900 000. SETTING: Organized Breast Screening Program in Nova Scotia, Canada. METHODS: Rates of participation, abnormal referrals, cancer detection rates, and benign:malignant (B:M) rates for core biopsy and surgical biopsy were calculated for asymptomatic women receiving a mammogram through the NSBSP 1991-2001. RESULTS: Of 192 454 mammograms performed on 71 317 women, 33% were aged 40 to 49 years, 39% aged 50 to 59 years, 23% aged 60 to 69 years, and 5% aged 70 years and over. Cancer detection rate increased in each age group respectively: 3.7, 5.8, 9.7, and 13.5 per 1000 population on first-time screens. The positive predictive value of an abnormal screen increased with increasing age groups. Benign breast surgery decreased with increased use of needle core breast biopsy (NCBB). Open surgery decreased from 25 to 6 surgeries per 1000 screens. Of 1519 open surgical procedures (1328 women), 878 cancers were removed, with 37% 10 mm or less, and 61% 15 mm or less. In 613 women in whom the node status was assessed, 79% were negative. CONCLUSION: A quality screening program incorporating NCBB in the diagnostic work-up is effective in the early detection of breast cancer and results in less open surgery, particularly in younger women.

[Role of dietary fibers in the nutritional management of chronic renal failure]. / Place des fibres alimentaires dans la prise en charge nutritionnelle de l'insuffisance rénale chronique.

During the past few decades, considerable attention has been given to the impact of nutrition on kidney disease. Although most dietary attempts to treat chronic renal failure (CRF) and to decrease uremia recommend a protein restriction, another dietetic approach, based on dietary fibers (DF), can lead to the same urea-lowering effect by increasing urea-nitrogen (N) excretion in stool with a concomitant decrease of the total N quantity excreted in urine. In fact, feeding DF results in a greater rate of urea N transfer from blood to large bowel, where it will be hydrolyzed by bacterial ureases before subsequent microflora metabolism and proliferation. Because elevated concentration of serum urea N have been associated with adverse clinical symptoms of CRF, these results suggested a possible usefulness of combining DF with a low protein diet to increase N excretion via the fecal route. These results have been shown in animal models of experimental renal failure and in CRF patients. Further investigations in this population of patients are currently in progress to study whether DF may be beneficial on CRF progression and on CRF terminal stage tolerance. A part of this work is financed by the French Society of Nephrology.

[Use of stress echocardiography in detecting silent myocardial ischemia in hemodialysis patients]. / Dépistage de l'ischémie myocardique silencieuse par échographie cardiaque de stress chez l'hémodialysé.

UNLABELLED: The chronic renal failure treated by hemodialysis is associated with a high incidence of prematured cardiovascular diseases, which represents the major causes of morbidity and mortality in hemodialysis patients. OBJECTIVE OF THE STUDY: To evaluate the interest of stress echocardiography for the detection of silent myocardial ischaemia in the chronic renal failure treated by hemodialysis. METHODS: 24 dobutamine stress echocardiography have been achieved in to patients having an average old of 61 +/- 11 years, 15 men and 3 women, with an average dialysis duration of 55 +/- 27 months. Only asymptomatic patients and those presenting an anomaly during the systematic annual echocardiography supervision have been included in this retrospective work. All echocardiography enregistrements have been achieved in the same center and by the same and experimented cardiologist. RESULTS: 75% of patients had an arterial hypertension antecedents, 65% were smokers, 50% had a dyslipidemia, 38% presented an arteriopathy of the inferior members, 30% had diabetes and 22% were obese; 8 (33.5%) stress echocardiographies were negatives. 6 patients have had 2 stress echocardiographies. A coronarography was realized in 16 patients and one of those was strictly normal (6.25% were false positive). 8 patients have had an angioplasty with stent making (1 simple stent, 7 double stent); 2 coronaries by-pass have been done in 2 patients. One patients refused surgery. Insignificant atheroumatous coronary lesions have been detected in 4 patients. In this study, the stress echocardiography enabled to detect a silent myocardial ischaemia in 15/16 patients (93.7%) and to treat 10/15 patients (66.5% including 20% by surgery). CONCLUSION: The sensibility of this test must be compared to the thallium scintigraphy coupled with dipyridamole as part of a larger prospective study.

[Proposal of a clinical prediction score for atheromatous renal artery stenosis]. / Proposition d'un score clinique de prédiction d'une sténose rénale athéromateuse.

UNLABELLED: Renal vascular pathologies are important causes of the chronic renal failure progression. This work aims to define retrospectively a score based on simple clinical and paraclinical helping to select atheromatous renal stenosis affected patients; 67 patients more than 50 years old have been explored by arteriography because of degradation of the renal function or hypertension: 45 of them had one, or many, significant stenosis of the renal arteries. Were analyzed: clinical data: age, weight, sex, blood pressure, previous ateromatous lesions (cardiac, peripheral, aortic), smoking, associated diabetes; biological data: serum cholesterol and creatinine, creatinine variation under angiotensin-coverting enzyme inhibitor or sodium depletion, kaliemia; radiologic data: kidney size through scanning, renal arterial and aortic calcifications on abdominal plain films and profile. The group with and without stenosis differed considerably for age (68.9 vs 64 years old, p < 0.05), smoking (26.3 vs 11.5 packet-year, p < 0.001), variation of creatinine after sensibilisation (140 mumol/l vs 17 mumol/l, p < 0.001), presence of arterial calcification (p < 0.001). A score taking in to account these four criteria was established with performances in terms of specificity and sensibility amounted to 83%. CONCLUSION: The reliable aspect of this score enabling to define a group seriously risking a renal stenosis must be checked through a prospective study.

Blockade of dorsal hippocampal kappa-opioid receptors increases blood pressure in normotensive and isolation-induced hypertensive rats.

Previous research in our laboratory has established a restraining role of the hippocampal kappa-opioid receptor system in the neural control of blood pressure. Chronic or acute hippocampal administration of kappa-agonists has been shown to reduce blood pressure. Isolation of male Sprague-Dawley rats provokes an increase in blood pressure, which has been proposed as a valid model of mild emotionally induced hypertension. It was the purpose of this study to investigate the blood pressure effects of dorsal hippocampal administration of nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist; in conscious male Sprague-Dawley rats subjected to isolation-induced hypertension. Chronic bi-hippocampal microinjection of nor-BNI (10 nmol per side, twice a day for 13 days) caused increases in systolic blood pressure in grouped rats from a mean of 125 to 148 mmHg, and in isolated rats from a mean of 125 to 151 mmHg. This hypertension was similar in magnitude to the increase observed after rats were isolated for 7 days and treated with vehicle in a similar fashion (mean systolic blood pressure 144 mmHg). The increases in blood pressure were accompanied by bradycardia. No significant responses were seen in the blood pressure of grouped rats treated with vehicle. The hypotensive response to a single hippocampal microinjection of the kappa-agonist U62, 066E (10 or 20 nmol) was prevented in anesthetized rats treated previously with nor-BNI, indicating that in the nor-BNI treated rats there was effective blockade of dorsal hippocampal receptors. These data suggest that the rat hippocampal kappa-opioid receptor system and the endogenous neuropeptide dynorphin may be involved in the central neural regulation of blood pressure.

[Smoking and atheromatous stenosis of the renal arteries]. / Tabac et sténoses athéromateuses des artères rénales.

UNLABELLED: Renal vascular pathologies are important causes of the chronic renal failure progression. In these pathologies, the role of smoking in so far as factor of risk was discussed. This work aims to evaluate the effect of smoking exposure on renal arteries of patients with both renal failure and hypertension. 67 patients more than 50 years old, having both renal failure and hypertension, have been explored by arteriography. The active smoking was required among all patients. Patients were classified in 2 groups: group (I) of 45 patients with one or more atheromatous stenoses of renal arteries considered to be significant and group (II) of 22 patients without significant atheromatous stenoses of renal arteries. [table: see text] 80.5% of patients of group (I) have smoked against only 44.4% in group (II). The fact that the presence of atheromatous stenoses of renal arteries was connected to the number of cigarettes and the exposure time, and not to the current comportment of patients towards smoking, this suggested a cumulative effect of smoking. CONCLUSION: This work shown a relation between the consumption of smoking and the existence of atheromatous stenoses of renal arteries, a reason moreover to fight against smoking. The prevention of smoking intoxication appears important to decrease the incidence of the renal vascular pathologies.

Fermentable carbohydrate and digestive nitrogen excretion.

BACKGROUND: Interventions that restrict protein intake lower plasma urea concentration and may slow the progression of renal failure. The question arises whether the effect of a dietary protein restriction could be reinforced by enrichment of the diet with fermentable carbohydrate because these carbohydrates may stimulate the extra-renal route of nitrogen (N) excretion through the digestive route. METHODS: The influence of fermentable carbohydrate and moderate protein restriction on N metabolism was investigated in a rat model of renal failure with ablation of 70% of renal mass compared with control rats with intact kidneys. Animals were adapted to diets varying with respect to nondigestible fermentable carbohydrate (0% or 10% fructooligosaccharide [FOS]) and with respect to protein content (10% or 18% casein). RESULTS: Feeding FOS led to a considerable enlargement of the cecum (increase in contents, wall thickness, and blood flow). These changes resulted in a concomitant enhancement of urea N uptake into the cecum and a decrease in plasma urea concentration (-30%). The extent of urea uptake by the cecum was influenced by plasma urea level that was determined by the dietary protein level and by the renal function. Thus, compared with control rats, the rate of urea uptake by the cecum and the total N excreted by the uremic rats was greater under all nutritional conditions. It is noteworthy that, when expressed as a percentage of total N excretion, fecal N excretion nearly doubled in rats adapted to the low-protein diets containing FOS. These effects occurred in both control rats and in uremic rats, in which a 22% decrease in urinary N was recorded as a result of FOS in addition to the low-protein diet. Globally, decreasing the amount of protein in the diet and adding a fermentable carbohydrate led to a decrease in urinary N excretion of more than 65% in uremic rats. CONCLUSION: These results suggest a possible usefulness for combining fermentable carbohydrate, such as FOS, with a low-protein diet to increase N excretion through the digestive route in detriment of the renal route. This may represent an efficient preventive measure to relieve the renal function in case of renal failure.

Deregulated platelet-activating factor levels and acetylhydrolase activity in patients with idiopathic IgA nephropathy.

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid mediator with potent inflammatory activities. PAF stimulates IgA synthesis by B cells while IgA aggregates enhance PAF production by neutrophils and mesangial cells. These results led us to investigate blood PAF levels and plasma acetylhydrolase (AHA, the PAF catabolic enzyme) activity in patients with idiopathic IgA nephropathy (IgAN). METHODS: PAF and AHA levels were investigated using the platelet aggregation assay and degradation of (3)H-labelled PAF, respectively. The genotype of AHA with regard to the G994-->T mutation in exon 9 was assessed by an allele-specific polymerase chain reaction. RESULTS: Blood PAF levels were significantly (P:=0.003, Mann-Whitney U:-test) elevated in IgAN patients (50.6+/-6.8 pg/ml, n=33) compared with healthy controls (18+/-5 pg/ml, n=18). In contrast, plasma AHA levels were significantly (P:=0.0001, Mann-Whitney U:-test) reduced in patients with IgAN (61+/-2 nmol/ml/min, n=51) compared with healthy controls (78+/-4 nmol/ml/min, n=53). G994-->T transversion in exon 9 of AHA was not found in any of the IgAN patients. CONCLUSION: Elevated circulating levels of PAF in IgAN patients might result from an insufficient AHA probably related to environmental factors rather than genetic ones. The mechanism and the precise role of the PAF/AHA deregulation in IgAN patients remain to be clarified.

Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: experimental bases.

During the past few years, considerable attention has been given to the impact of nutrition on kidney disease. The question arises of whether the effect of a moderate dietary protein restriction could be reinforced by enrichment of the diet with fermentable carbohydrates. Feeding fermentable carbohydrates may stimulate the extrarenal route of nitrogen (N) excretion through the fecal route. Such an effect has been reported in several species, including healthy humans and patients with chronic renal failure (CRF). Furthermore, studies of these subjects show that the greater fecal N excretion during the fermentable carbohydrate supplementation period was accompanied by a significant decrease in plasma urea concentration. In animal models of experimental renal failure, the consumption of diets containing fermentable carbohydrates results in a greater rate of urea N transfer from blood to the cecal lumen, where it is hydrolyzed by bacterial urease before subsequent microflora metabolism and proliferation. Therefore, this results in a greater fecal N excretion, coupled with a reduction in urinary N excretion and plasma urea concentration. Because elevated concentrations of serum urea N have been associated with adverse clinical symptoms of CRF, these results suggest a possible usefulness of combining fermentable carbohydrates with a low-protein diet to increase N excretion through the fecal route. Further investigations in this population of patients of whether fermentable carbohydrates in the diet may be beneficial in delaying or treating the symptoms and chronic complications of CRF will certainly emerge in the future. This should be realized without adversely affecting nutritional status and, as far as possible, by optimizing protein intake for the patients without being detrimental to renal function.