Why is coronary heart disease of uraemic patients so frequent and so devastating?

On September 6, 2001, Professor Fernando Valderrabano (Hospital Gregorio Mara?on, Madrid) died at the age of 59 years. He was a leading figure in Spanish nephrology, a full professor of Medicine/Nephrology at the University Complutense of Madrid, and an outstanding scientist who published more than 300 articles in medical journals. He was a very intelligent and cultured person, and a man of great style who enjoyed a wide range of hobbies and interests in addition to his medical work. All his colleagues and friends mourn his passing.     

Ventricular arrhythmias before and late after aortic valve replacement

The influence of aortic valve replacement on the incidence of ventricular arrhythmias was studied by 24-hour Holter electrocardiographic monitoring in 45 patients immediately before and 14 ± 7 months after operation. Ventricular arrhythmias were graded according to the Lown criteria. Preoperative left ventricular (LV) ejection fraction (EF) was determined by angiography and postoperative LVEF by gated blood pool scintigraphy. Repetitive ventricular arrhythmias (Lown grade 4A/B) were associated with a reduced LVEF (< 55%) before and after operation. In 24 patients with preoperative normal LVEF (>- 55%) (group A), mean LVEF remained unchanged after operation (72% vs 71 %). Pre- and postoperative ventricular premature complex (VPC) frequency (45 ± 99 vs 39 ± 94 VPC/24 hours and grade (1.3 vs 1.4) were not significantly different. However, in 17 patients with preoperative impaired LVEF (< 55%) (group B, LVEF preoperatively 40 ± 8%) and marked postoperative improvement (> 10%) (LVEF postoperatively 64 ± 7%), mean VPC frequency decreased from 536 to 69 VPCs/24 hours and mean VPC grade was reduced from 3.8 to 1.5. Complex VPCs were found preoperatively in all 17 patients of group B, but in only 5 patients after operation. Four patients had a reduced LVEF preoperatively and it did not improve postoperatively (group C). Postoperative Holter monitoring detected ventricular tachycardia in all 4 patients.This study indicates that repetitive VPCs are infrequent in patients with normal LVEF before and late after aortic valve replacement. In patients with impaired LVEF and complex VPCs preoperatively, the postoperative improvement of LV function is usually accompanied by a reduction of frequent and complex VPCs.     

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

Background

Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS).

Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis

Journal of Neurology - Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress...     

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells

BACKGROUND: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms. METHODS: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured. ATP release also was induced by alpha1- and alpha2-adrenergic agonists. [3H]-thymidine uptake was tested in human visceral glomerular epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44) activation in vGEC and kidney cortex. The involved P2-receptors were characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve stimulation and alpha-adrenergic agonists induced release of ATP from human kidney cortex. Seventy-five percent of the ATP released originated from non-neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect. ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal sources. ATP has mitogenic effects in vGEC and therefore the potential to contribute to progression in chronic renal disease. The pattern of purinoceptor agonist effects on DNA synthesis together with the mRNA expression suggests a major contribution of a P2Y1-like receptor.     

Intraperitoneal protein injection in the axolotl: the amphibian kidney as a novel model to study tubulointerstitial activation

BACKGROUND: A substantial body of experimental evidence suggests that protein loading causes activation of proximal tubular epithelial cells with consecutive interstitial fibrosis. These studies have mostly been performed using mammalian in vivo models of glomerular damage or tissue cultures of mammalian tubulointerstitial cells. The kidney of the axolotl contains not only closed nephrons, but also nephrons with ciliated peritoneal funnels called nephrostomes that have access to the peritoneal fluid. Injection of protein into the peritoneal cavity fails to expose closed nephrons to a protein load, but causes selective uptake and transient storage of proteins in tubular epithelial cells of nephrons with nephrostomes. The purpose of the present study was to determine whether (a) the axolotl kidney can be used as a model to assess protein uptake by tubular cells in vivo in the absence of glomerular damage, and (b) this is accompanied by any evidence of tubular epithelial cell activation and interstitial fibrosis. METHODS: Male and female axolotl (80 to 120 g of weight) were given a daily intraperitoneal injection of 1.5 mL endotoxin-free calf serum or saline as control. Kidneys were harvested after 4 or 10 days using perfusion fixation for light microscopy (fibrous tissue stain) and saline perfusion for immunohistochemistry (fibronectin, TGF-beta and collagen I). RESULTS: The findings document selective storage of protein and lipids, progressive with time, in proximal tubular epithelial cells of nephrons draining the coelomic cavity. In addition, progressive focal accumulation of fibrous tissue was noted around protein-storing tubules. Immunohistochemical staining demonstrated the presence of fibronectin and TGF-beta in the tubular epithelial cells and interstitial cells. CONCLUSION: The axolotl kidney provides a novel in vivo model to study tubulointerstitial activation and induction of interstitial fibrosis by protein loading. The findings are independent of alterations of glomerular function that may have potential confounding effects on peritubular hemodynamics, pO2, cell traffic, etc.