Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis

BACKGROUND: Acute tubular necrosis (ATN) has high mortality, especially in patients who require renal replacement therapy (RRT). We prospectively studied the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins and enzymes as predictors of a need for RRT in ATN. METHODS: In 73 consecutive patients with initially nonoliguric ATN, we measured urinary excretion of alpha(1)- and beta(2)-microglobulin, cystatin C, retinol-binding protein, alpha-glutathione S-transferase, gamma-glutamyltransferase, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase early in the course of ATN. RESULTS: Twenty-six patients (36%) required RRT a median of 4 (interquartile range, 2-6) days after detection of proteinuria and enzymuria. Patients who required RRT had higher urinary cystatin C and alpha(1)-microglobulin [median (interquartile range), 1.7 (1.2-4.1) and 34.5 (26.6-45.1) g/mol of creatinine] than patients who did not require RRT [0.1 (0.02-0.5) and 8.0 (5.0-17.5) g/mol of creatinine]. Urinary excretion of cystatin C and alpha(1)-microglobulin had the highest diagnostic accuracies in identifying patients requiring RRT as indicated by the largest areas under the ROC curves: 0.92 (95% confidence interval, 0.86-0.96) and 0.86 (0.78-0.92), respectively. Sensitivity and specificity were 92% (95% confidence interval, 83-96%) and 83% (73-90%), respectively, for urinary cystatin C >1 g/mol of creatinine, and 88% (78-93%) and 81% (70-88%) for urinary alpha(1)-microglobulin >20 g/mol of creatinine. CONCLUSION: In nonoliguric ATN, increased urinary excretion of cystatin C and alpha(1)-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.     

Muscle ultrasound in children: normal values and application to neuromuscular disorders

In this study, 105 healthy children (45 to 156 months old, 57 girls) were examined using ultrasound (US) imaging to obtain reference values of muscle dimensional and aspect parameters. We measured biceps and quadriceps sizes and subcutaneous tissue thickness. To quantify muscle aspect, we calculated muscle density, inhomogeneity and white-area index by digital image analysis. Age-, weight- and gender-dependencies were discussed. We demonstrated earlier that the complete set of parameters allows for differentiation between myopathies and neuropathies in adults, with high sensitivity. In this study, we investigated if these parameters have additional value in the diagnostic evaluation of 36 children with proven neuromuscular disease (20 Duchenne muscular dystrophy, 16 neuropathies). We found that density analysis provides a sensitive method for distinguishing between healthy children and children with neuromuscular disorders. We have also found that more detailed aspect analysis is necessary to further distinguish between these types of neuromuscular disorders in children. In conclusion, this set of normal muscle parameters can be used to help diagnose neuromuscular disorders in children. It will also facilitate follow-up in disease progression and therapy.     

Severe vagal response after endotoxin administration in humans

Objective Endotoxin administration to humans is a common means to study systemic inflammation. Worldwide, thousands of volunteers have received endotoxin, and adverse events are rarely reported. The aim of this report was to increase awareness of specific risks of the intravenous administration of endotoxin to human volunteers.Design Report of four cases who developed severe bradycardia or protracted asystole after administration of endotoxin. Interviews with investigators at three large centers that conduct normal volunteer endotoxin studies.Setting Clinical research unit.Cases Four subjects developed severe bradycardia or protracted asystole, approximately 1 h after administration of endotoxin. Further analyses revealed that the subjects had a history of vasovagal syncope or a positive head-tilt test, indicating increased vagal sensitivity. Relative volume depletion associated with fasting overnight may have predisposed these subjects to this condition.Conclusions These responses are very rare and are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough screening regarding a history of vagal sensitivity and liberal oral or intravenous fluid administration prior to and during the endotoxin challenge may decrease the risk of these events.P. Pickkers is a recipient of a Clinical Fellowship grant of the Netherlands Organisation for Scientific Research (ZonMw)     

Dietary intakes of adults in the Netherlands by childhood and adulthood socioeconomic position

OBJECTIVE: To determine whether there are socioeconomic differences in the intakes of total fat, fatty acids and fruit among adults in the Netherlands using childhood (parental) and participant's own socioeconomic position (SEP). Furthermore, to quantify the independent effects of childhood and adulthood SEP on dietary behavior in adulthood. DESIGN: Cross-sectional study among participants in the GLOBE study. SUBJECTS: A total of 2512 men and women, aged 25-78 y, living in a region in the southeast Netherlands. METHODS: Dietary intakes were collected by an interviewer-administered quantitative food frequency questionnaire. Average daily intakes of total energy, total, saturated, monounsaturated, polyunsaturated fat and fruit were calculated. The highest educational level was used to classify the participant's adulthood SEP. Parental indicators (mother's education and father's occupation when participants were 12 y of age) were used to classify childhood SEP. RESULTS: Males with lower levels of education had moderately higher energy intakes than their more educated counterparts, but did not differ in their intakes of total fat, fatty acids and fruit. Among females, the least educated groups had marginally higher intakes of total and monounsaturated fat than the most educated group, and were less likely to consume fruit. For most of these significant differences, the participant's own education demonstrated independent effects that were consistent with chronic disease inequalities. A small residual effect of mother's education was also demonstrated for intakes of some nutrients for males and females, and for fruit consumption among females. However, the effect size of mother's education was rather small and not always consistent with disease inequalities. CONCLUSIONS: The results imply that socioeconomic disparities in intakes of some dietary factors may contribute to inequalities in chronic disease. Adulthood SEP potentially has a more direct influence on dietary intake inequalities than childhood SEP.     

The Dutch Heart Health community intervention 'Hartslag Limburg': results of an effect study at individual level

'Hartslag Limburg' (Dutch for Heartbeat Limburg), a regional cardiovascular diseases (CVD) prevention program, integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors. The present paper focuses on the effects of the community intervention on fat intake and physical activity. The project was based on community organization principles and health education theories and methods. In order to implement the intervention, nine local Health Committees were set up, each organizing activities that facilitate and encourage people to adopt a healthier lifestyle. A pre-test-post-test control group design with two post-tests was used to evaluate the intervention. At baseline, representative random cohort research samples were selected in the Maastricht region and in a control region. Data on fat intake and physical activity, and on the psychosocial determinants of these behaviors, were gathered by means of mail surveys. The present study indicates that the intervention had a significant effect on fat reduction, especially among respondents aged 相似文献   

Acceptability and feasibility of an interactive computer-tailored fat intake intervention in Belgium

In order to reduce the risk of chronic diseases health authorities recommend restricting fat intake to 30% of the total energy uptake. However, fat intake in Belgium is much higher warranting interventions aimed at reducing fat intake. Tailored interventions have shown to be promising; however, studies on effectiveness of interactive computer-tailored systems are needed. We investigated the acceptability and feasibility of a recently developed interactive computer-tailored fat reduction intervention. Differences in the reported acceptability and feasibility according to demographic and stages of change were explored. Participants (n = 220) completed a computerized questionnaire, and received a personal fat intake advice, which was almost immediately displayed on screen. They also completed an evaluation questionnaire, during and after they ran the tailored program, with questions on the quality, user-friendliness and applicability of the program. Participants rated the program positively on all aspects. No significant differences in acceptability and feasibility scores were found according to sex, education levels and computer literacy. Although several significant differences were found between age groups and stages of change (oldest group, contemplators and preparators were more positive about the program), the importance of these differences is probably not great, since acceptability and feasibility scores for the different age groups and stages of change were always very high. These results suggest that the computer-tailored intervention is an acceptable and feasible tool for reducing fat intake in a general population in Belgium.     

Changes in myocardial collagen content before and after left ventricular assist device application in dilated cardiomyopathy

Background The purposes of this study were to confirm the changes in myocardial collagen level after left ventricular assist device (LVAD) support in dilated cardiomyopathy (DCM), find the relation between these changes and prognosis, and test a practical method to assess the level of myocardial collagen.Methods Left ventricular samples were collected from DCM patients with different prognosis (transplanted group n=8, weaning group n=10) at the time when the LVADs were implanted and again during cardiac transplantation (n=8). The level of neutral salt soluble collagen (NSC) and acid soluble collagen (ASC) was measured by Sircol collagen assay, and that of total collagen and insoluble collagen (ISC) by quantification of hydroxyproline (Hyp). Serum samples were collected from a portion of these patients (transplanted group, n=6; weaning group n=7) at the time the LVADs were implanted, 1 month after implantation and on explantation. Circulating concentration of carboxy-terminal propeptide of type Ⅰ procollagen (PⅠCP), amino-terminal propeptide of type Ⅰ procollagen (PⅠNP), amino-terminal propeptide of type Ⅲ procollagen (PⅢNP) and type Ⅰ collagen telopeptide (ⅠCTP) were measured by the equilibrium type radioimmunoassay. Results Before LVAD implantation the level of NSC and ISC in the weaning group was higher but ASC in the transplanted group was lower than in the controls (P<0.05). After LVAD support, the level of total collagen was higher, but ASC was also lower in the transplanted group than in the controls (P<0.05). In comparison of the pre- and post-LVAD subgroups of the transplanted and weaning groups, all collagen fraction levels before LVAD implantation were lower in the transplanted group than in the weaning group (P<0.05); but this difference disappeared after LVAD support. Comparison of the pre- and post-LVAD subgroups of the transplanted group showed increased level of NSC and total collagen after LVAD support. The changes of serum peptide concentration showed that PⅢNP increased constantly in the transplanted group, but PⅠCP and PⅠNP increased in the weaning group after LVAD implantation. Conclusions The changes in myocardial collagen level as a sign of myocardial interstitial remodeling in DCM are not involved with total collagen but invalved with collagen fractions, and they are related to prognosis. The changes of myocardial collagen content and serum procollagen peptide after LVAD support can be regarded as an expression of the reverse of maladaptive myocardial interstitial remodeling.     

Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes

Context  Both bone mineral density (BMD) and fracture risk have a strong genetic component. Estrogen receptor (ESR1) is a candidate gene for osteoporosis, but previous studies of ESR1 polymorphisms in this field were hampered by small sample size, lack of standardization, and inconclusive results. Objective  To generate large-scale evidence on whether 3 common ESR1 polymorphisms (intron 1 polymorphisms XbaI [dbSNP: rs9340799] and PvuII [dbSNP: rs2234693] and promoter TA repeats microsatellite) and haplotypes thereof are associated with BMD and fractures. Design and Setting  Meta-analysis of individual-level data involving standardized genotyping of 18 917 individuals in 8 European centers. Main Outcome Measures  BMD of femoral neck and lumbar spine; all fractures and vertebral fractures by genotype. Results  No between-center heterogeneity was observed for any outcome in any genetic contrast. None of the 3 polymorphisms or haplotypes had any statistically significant effect on BMD in adjusted or unadjusted analyses, and estimated differences between genetic contrasts were 0.01 g/cm² or less. Conversely, we found significant reductions in fracture risk. In women homozygous for the absence of an XbaI recognition site, the adjusted odds of all fractures were reduced by 19% (odds ratio, 0.81 [95% CI, 0.71-0.93]; P = .002) and vertebral fractures by 35% (odds ratio, 0.65 [95% CI, 0.49-0.87]; P = .003). Effects on fractures were independent of BMD and unaltered in adjusted analyses. No significant effects on fracture risk were seen for PvuII and TA repeats. Conclusions  ESR1 is a susceptibility gene for fractures, and XbaI determines fracture risk by mechanisms independent of BMD. Our study demonstrates the value of adequately powered studies with standardized genotyping and clinical outcomes in defining effects of common genetic variants on complex diseases.      

Absence of mouse pleiotrophin does not affect bone formation in vivo

Pleiotrophin (Ptn) is an extracellular matrix protein that regulates hippocampal synaptic plasticity and learning behavior in vivo. Since the overexpression of Ptn in transgenic mice leads to increased bone formation, we analyzed whether a deficiency in Ptn expression would have a negative effect on bone remodeling. Bones from Ptn-deficient mice and wild-type littermates were analyzed using radiography, μCT imaging and undecalcified histology. Biomechanical stability was determined in a three-point-bending assay. Cellular activities were assessed using dynamic histomorphometry and the determination of urinary collagen degradation products. Skeletons of Ptn-deficient mice have no gross abnormalities, displayed a normal size, and showed no differences in growth plate organization compared to wild-type littermates. There were no obvious differences in bone mass as determined by radiographic and μCT imaging. The absence of a bone remodeling phenotype in Ptn-deficient mice was further confirmed using static histomorphometry and biomechanical testing. Finally, the number, morphology, and function of osteoclasts, osteoblasts, and osteocytes were not altered in Ptn-deficient mice compared to wild-type littermates. The complete skeletal analysis of Ptn-deficient mice presented here demonstrates that the lack of Ptn in mice does not affect bone formation in vivo. Therefore, Ptn does not play a significant role in normal bone physiology.