The aluminum content of bone increases with age, but is not higher in hip fracture cases with and without dementia compared to controls

Aluminum is considered a potentially toxic metal, and aluminum poisoning may lead to three types of disorders: aluminum-induced bone disease, microcytic anemia and encephalopathy. This is well known in patients with chronic renal failure, but since healthy subjects with normal renal function retain 4% of the aluminum consumed, they are also at risk of long-term low-grade aluminum intoxication. Included in this study were a total of 172 patients (age range 16–98 years) with the aim of examining whether aluminum accumulates in bone with increasing age. Additionally, we aimed to investigate whether the aluminum content of bone differs between controls and hip fracture cases with and without dementia, in particular in those with Alzheimers disease. During operations for all cases, bone biopsies were taken with an aluminum-free instrument from the trabecular bone. The samples were measured for their content of aluminum using an inductively coupled mass spectrometer. We found an exponential increase in aluminum content of bone with age. The average aluminum values, adjusted for age, were similar in men and women (P=0.46). No significant differences in sex- and age-adjusted mean aluminum values between the controls and the hip fracture cases with (P=0.72) and without (P=0.33) dementia could be detected. The average aluminum concentration among cases with Alzheimers disease was also similar to the values of hip fracture patients with other types of dementia (P=0.47). Odds ratios of hip fracture for each quartile of aluminum content in bone were also estimated to detect non-linear effects, but we did not find any statistically significant association remaining after age and sex adjustment. Thus, our results indicate that we accumulate aluminum in bone over our life span, but this does not seem to be of major pathogenetic significance for the occurrence of hip fracture or dementia.     

Normalization of endothelial dysfunction following renal transplantation is accompanied by a reduction of circulating visfatin/NAMPT. A novel marker of endothelial damage?

Abstract:  Endothelial dysfunction is strongly linked to cardiovascular disease and outcome of patients with chronic kidney disease. We hypothesized that decreased inflammatory activity and increased adiponectin following transplantation could be one mechanism for a better endothelial health. Fifty-eight living donor kidney transplant non-diabetic recipients, 31 (23 male, 29 ± 5 yr) on cyclosporine A and 27 (10 male, 26 ± 5 yr) on tacrolimus immunsupression, were studied longitudinally. Visfatin, adiponectin, high sensitive C-reactive protein (hsCRP) levels, brachial artery flow mediated dilatation (FMD) and nitroglycerine mediated dilatation were measured before transplantation and on the 30th and 90th day after transplantation. Pre-transplantation visfatin, adiponectin and FMD values of patients were significantly higher than those of the controls (p < 0.001 for all). All values decreased significantly 30 and 90 d post-transplantation. Plasma visfatin and adiponectin, correlated negatively with FMD levels 90 d both before and after kidney transplantation (p < 0.001 for both). Endothelial function improved during the first month after transplantation, and the degree of improvement correlated to reductions in circulating visfatin, adiponectin and hsCRP levels. Of interest, the intracellular enzyme visfatin was the strongest predictor of FMD both before and after kidney transplantation and may thus reflect endothelial cell damage directly.     

Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre.

BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.     

终末期肾衰竭患者血清胎球蛋白A水平改变与临床预后的关系

目的探讨终末期肾衰竭(ESRD)患者在透析前以及透析年后血清胎球蛋白1A浓度的改变以及其与临床表现及预后之间的关系。方法,247例透析前ESRD患者接受血清胎球蛋白A及有关生化检查,其中131例在透析1年后再次检测。此外,用B超检测颈动脉斑块。患者随访期中位数为29.6(范12.1￣42.0)个围月。70例健康人入选对照组。结果ESRD患者血胎球蛋白A水平较正常对照组明显降低(P<0.05)。透析前血胎球蛋白A水平与血白蛋白(P<0.01)、IL鄄6(P<0.05)、血钙磷乘积(P<0.05),尤其是与血磷水平(P<0.05)相关。炎症、营养不良患者血胎球蛋白水平较低(AP<0.05)。颈动脉有斑块的患者血胎球蛋白浓度较无斑块者明显降低(AP<0.01)。透析1年后胎球蛋白A血浓度较治疗前相比明显降低(131例,P<0.01)。62%患者经过1年的肾脏替代治疗后胎球蛋白A水平较治疗前相比明显下降。无论是在治疗前还是在治疗1年后,随访中存活的患者胎球蛋白水平显著地高于死亡者(AP<0.05)。结论ESRD患者低胎球蛋白A水平与营养不良、炎症、动脉粥样硬化以及病死率相关,经肾脏替代治疗后胎球蛋白A水平仍持续下降。胎球蛋白A水平是ESRD患者预后的一个重要独立因素。     

Regeneration of human auditory nerve. In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion

Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage.     

Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.     

Physical Functioning,Mental Health,and Quality of Life in Different Congenital Heart Defects: Comparative Analysis in 3538 Patients From 15 Countries

BackgroundWe compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects.MethodsIn the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect.ResultsPatients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%).ConclusionsSome types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes.     

Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

Granzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.