Acute effect of CyA A (Neoral) on large artery hemodynamics in renal transplant patients

BACKGROUND: CyA A (CyA) may induce intrarenal vasoconstriction, endothelial dysfunction, and hypertension. There are only two contradictory reports describing the acute effect of CyA on renal resistances measured by color Doppler flowmetry. Therefore, we studied the acute influence of oral CyA on arterial haemodynamics by assessing simultaneous changes in blood pressure, applanation tonometry-derived pulse wave analysis and duplex ultrasound-derived intrarenal resistance indices. METHODS: Augmentation index (AIx) (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse pressure = AIx) was determined from contour analysis of arterial waveforms recorded by applanation tonometry using the AtCor device in 18 live-related renal transplants (11 females/7 males, age = 32.0 +/- 8.1 years, transplantation duration = 17.5 +/- 16.1 months, and mean serum creatinine = 133 +/- 70 micromol/L). All studies were performed just before (C0), and 2 hours after (C2) the oral administration of CyA. At the same C0 and C2 moments the resistive index (RI) = (peak systolic frequency shift - minimum diastolic frequency shift)/peak systolic frequency shift, and pulsatility index (PI) = (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift were calculated from Doppler recorded waveforms. RESULTS: Blood pressure and heart rate did not differ significantly at C0 and at C2 serum levels: 134.3/82.9 vs. 128.1/80.0 mm Hg and 72.0 vs. 71.0 beats/min, respectively, despite a marked increase in whole blood concentration (CyA(C0)= 90.8 +/- 45.9 vs. CyA(C2)= 547.4 +/- 251.3 ng/mL) (P= 0.05). Mean AIx fell significantly from 17.2 +/- 13.8 to 12.9 +/- 14.2 (P < 0.0001). There was no correlation between the extent (expressed as absolute or relative change) of the measured alteration in AIx and total administered CyA dose, or increment in blood level between C0 and C2. In support, the intake of CyA did not induce a significant increase in Doppler resistance (RI(C0)= 0.68 +/- 0.08 vs. RI(C2)= 0.70 +/- 0.09) and pulsatility indices (PI(C0)= 1.32 +/- 0.31 vs. PI(C2)= 1.33 +/- 0.28). Finally, three patients were studied twice (>1 week): one under two levels of creatinine, one with no antihypertensives, and a third receiving verapamil initially. All these maintained a significant decrease in AIx at C2 from C0 supporting the reproducibility of the phenomenon. CONCLUSION: We demonstrate that Neoral CyA acutely improves large arterial compliance function and does not induce an acute rise in intrarenal resistance in stable renal transplant subjects with normal renal function. We speculate that there may be an effect of vitamin E, the diluent vehicle in which CyA is carried (1000 IU/100 mg CyA), shown to improve endothelial function.     

Oxalate is toxic to renal tubular cells only at supraphysiologic concentrations

BACKGROUND: Oxalate-induced tissue damage may play an initiating role in the pathophysiology of calcium oxalate nephrolithiasis. The concentration of oxalate is higher in the renal collecting ducts ( approximately 0.1 to 0.5 mmol/L) than in the proximal tubule ( approximately 0.002 to 0.1 mmol/L). In the present investigation, we studied the damaging effect of oxalate to renal proximal and collecting tubule cells in culture. METHODS: Studies were performed with the renal proximal tubular cell lines, LLC-PK1 and Madin Darby canine kidney II (MDCK-II), and the renal collecting duct cell lines, rat renal cortical collecting duct (RCCD1) and MDCK-I. Confluent monolayers cultured on permeable growth substrates in a two-compartment culture system were apically exposed for 24 hours to relatively low (0.2, 0.5, and 1.0 mmol/L) and high (5 and 10 mmol/L) oxalate concentrations, after which several cellular responses were studied, including monolayer morphology (confocal microscopy), transepithelial electrical resistances (TER), prostaglandin E(2) (PGE(2)) secretion, lactate dehydrogenase (LDH) release, DNA synthesis ([(3)H]-thymidine incorporation), total cell numbers, reactive oxygen species (H(2)O(2)) generation, apoptotic (annexin V and DNA fragmentation), and necrotic (propidium iodide influx) cell death. RESULTS: Visible morphologic alterations were observed only at high oxalate concentrations. TER was concentration-dependently decreased by high, but not by low, oxalate. Elevated levels of PGE(2), LDH, and H(2)O(2) were measured in both cell types after exposure to high, but not to low oxalate. Exposure to high oxalate resulted in elevated levels of DNA synthesis with decreasing total cell numbers. High, but not low, oxalate induced necrotic cell death without signs of programmed cell death. CONCLUSION: This study shows that oxalate is toxic to renal tubular cells, but only at supraphysiologic concentrations.     

The Effects of Neuromuscular Electrical Stimulation Training on Abdominal Strength,Endurance, and Selected Anthropometric Measures

We studied the effects of self-administered neuromuscular electrical stimulation (NMES) on changes in strength, endurance, selected anthropometric measures, and subject’s perceived shape and satisfaction of the abdominal wall. Twenty-four adults (experimental group) stimulated their abdominals 5 days per week (20-40 minutes per session) for 8 weeks and refrained from engaging in any additional exercise during the study. A control group (N=16) refrained from exercising the abdominals or engaging in any other exercise training during the study. Subjects were tested at the beginning, mid-point, and end of the study. Isometric strength of the abdominal muscles was tested using a isokinetic dynamometer, endurance was measured using the ACSM curl-up test, abdominal circumference was measured using a steel tape measure, and body shape and satisfaction were assessed via questionnaire. The stimulation group had a 58% increase in abdominal strength, whereas the control group did not change. The stimulation group also had a 100% increase in abdominal endurance versus a 28% increase in the control group. Waist circumference decreased by of 3.5 cm in the stimulation group compared to no significant change in the control group. All 24 subjects in the stimulation group felt that their midsections were more “toned” and “firmed” and 13/24 (54%) felt that their posture had improved as a result of the stimulation. None of the control group subjects reported changes in these parameters. There were no significant differences in body weight, BMI, or skinfold thickness over the course of the study in either group. NMES, as used in the current study, resulted in significant improvements in the muscular strength and endurance of the abdominal region, as well as subject’s perceived shape and satisfaction of the mid-section.

Key Points

• Electrical muscle stimulation (EMS) was effective in increasing muscle strength and endurance
• All subjects perceived their abdominal muscles to be firmer and more toned as a result of EMS
• Abdominal and waist girth was also significantly reduced, despite no changes in body weight or subcutaneous fat

Key Words: Fitness, training, isometric     

Percutaneous nephrolithotomy for treating renal calculi in children

OBJECTIVE: To report our experience with the percutaneous management of renal stone disease in children. PATIENTS AND METHODS: The medical and radiological records of children up to 18 years old who were treated for renal calculi by percutaneous nephrolithotomy (PCNL) at our institution between March 1995 and April 2003 were reviewed. For stone removal a special paediatric 18 F access sheath was used. RESULTS: In all, 26 PCNLs were used in 23 patients (10 boys and 13 girls, aged 1.7-16.8 years). The presenting symptoms were urinary tract infection, abdominal pain and/or haematuria. Of the 23 patients, 17 (75%) had associated metabolic disease or underlying urological anatomical abnormalities. Urinary tract infections were found in 15 patients (65%). The mean (range) stone burden was 6.0 (0.5-18.2) cm2, and the operative duration 127 (50-260) min. The primary stone-free rate was 58%, which increased to 81% after treating residual fragments. One blood transfusion was required and one patient developed urosepsis after PCNL, which was treated with antibiotics. CONCLUSION: PCNL is an effective alternative for treating renal stones in children, and is the treatment of choice for stones refractory to extracorporeal shock wave lithotripsy.     

Socioeconomic factors and risk of hospitalization with infectious diseases in 0- to 2-year-old Danish children

Although the association between low socioeconomic status and illness in childhood is well known, the impact of socioeconomic factors on risk and frequency of hospitalizations for infectious diseases, the most frequent disease category, during the first 2 years of life has scarcely been studied. Through linkage of records drawn from public administrative and health registries, we conducted a population-based cohort study of 5024 Danish children born in 1997 to examine the frequency of hospitalization for infectious diseases in very young children. The main exposure variables, adjusted for potential confounding factors, were mother’s education level, household income, and cohabitation status. The outcome was number of hospital admissions (0, 1–2, or 3+) for infectious diseases. A total of 737 children (14.7%) were admitted to hospital 1–2 times, and 83 (1.6%) were admitted 3–10 times. The risk of hospitalization was increased in children of mothers with a low level of education compared with vocational education (1–2 admissions: adjusted odds ratio (OR) 1.3 (95% confidence interval [CI]: 1.1–1.6). Children from low-income families had an increased risk of 3 or more admissions (low cf middle income: adjusted OR 2.0 [95% CI: 0.6–6.0]). Children of single mothers had an increased risk of hospitalization (1–2 admissions: adjusted OR 1.7 [95% CI: 1.1–2.6]. We found the highest risk of hospitalization for infectious diseases in children of mothers with only basic schooling, and particularly among those coming from single parent homes with a low income.     

An introduction to critical paths

A critical path defines the optimal sequencing and timing of interventions by physicians, nurses, and other staff for a particular diagnosis or procedure. Critical paths are developed through collaborative efforts of physicians, nurses, pharmacists, and others to improve the quality and value of patient care. They are designed to minimize delays and resource utilization and to maximize quality of care. Critical paths have been shown to reduce variation in the care provided, facilitate expected outcomes, reduce delays, reduce length of stay, and improve cost-effectiveness. The approach and goals of critical paths are consistent with those of total quality management (TQM) and can be an important part of an organization's TQM process.     

Association of proopiomelanocortin gene polymorphisms with obesity in the IRAS family study

Proopiomelanocortin (POMC) has been found to be associated with rare Mendelian forms of obesity in children, and, in linkage studies, genomic regions containing the POMC locus have been linked to leptin levels, a predictor of obesity, in white, Mexican-American, and African-American families. POMC polymorphisms have not been investigated in detail for association with obesity in the general population. Five single nucleotide polymorphisms (SNPs) (G-3460C, C17T, G3473A, C3755T, and A7069G) were genotyped on 811 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study and tested for association with multiple obesity quantitative traits. General and family-based association analyses for each individual SNP and for haplotypes were performed using the generalized estimating equation and quantitative pedigree disequilibrium test (QPDT), respectively. Modest but consistent associations were observed for SNP C3755T, with p values ranging from 0.011 to 0.045 for association with BMI, waist, visceral adipose tissue, and subcutaneous adipose tissue. G-3460C, G3473A, and A7069G were also found to be associated with additional obesity measurements (p value 0.025 to 0.04), with comparable levels of evidence observed for linkage disequilibrium between these traits and these SNPs. Results of the haplotype analyses were also consistent with the single SNP analysis, with haplotypes containing C3755T showing the greatest evidence of association (p values ranging 0.004 to 0.048). Monte Carlo simulations (gene dropping) that account for the number of comparisons and the correlation structure indicate that the multivariate significance for these obesity traits with these polymorphisms was p = 0.0091. Collectively, the POMC polymorphisms showed consistent evidence for association with obesity traits in Hispanic Americans across several analytical approaches using SNP and haplotype analysis. These results support the hypothesis that POMC contributes genetically to the development of obesity.     

Heritability of body composition measured by DXA in the diabetes heart study

OBJECTIVE: The purpose of this study was to investigate the heritability of body composition measured by DXA in the Diabetes Heart Study (DHS). RESEARCH METHODS AND PROCEDURES: Participants were 292 women and 262 men (age, 38 to 86 years; BMI, 17 to 57 kg/m(2)) from 244 families. There were 492 white and 49 African-American sibling pairs. DXA measurements of percentage fat mass (FM), whole body FM, and lean mass (LM), as well as regional measurements of trunk fat mass (TFM) and appendicular lean mass (ALM), were obtained. Heritability of FM, LM, and BMI were estimated using Sequential Oligogenic Linkage Analysis Routines. RESULTS: After adjusting for age, gender, ethnicity, and height, the heritability estimates of various compositional attributes were %FM = 0.64, whole body FM = 0.71, TFM = 0.63, whole body LM = 0.60, ALM = 0.66, and BMI = 0.64 (all p < 0.0001). Additional adjustment for diabetes status, smoking, dietary intake, and physical activity resulted in only minor changes in the heritability estimates (h(2) = 0.63 to 0.72, all p < 0.0001). Furthermore, heritability of TFM after additional adjustment for whole body FM was significant (h(2) = 0.55, p < 0.0001), and heritability of ALM after additional adjustment for whole body LM was also significant (h(2) = 0.51, p < 0.0001). DISCUSSION: These data suggest that FM and LM measured by DXA are highly heritable and can be effectively used in designing linkage studies to locate genes governing body composition. In addition, regional distribution of FM and LM may be genetically determined.     

Estimate of illnesses from Salmonella enteritidis in eggs, United States, 2000

Results from our model suggest that eating Salmonella enterica serovar Enteritidis-contaminated shell eggs caused 182,060 illnesses in the United States during 2000. Uncertainty about the estimate ranged from 81,535 (5th percentile) to 276,500 illnesses (95th percentile). Our model provides but 1 approach for estimating foodborne illness and quantifying estimate uncertainty.