To study the feasibility of creating a radiocephalic hemodialysis fistula in elderly and diabetic patients, we prospectively studied 176 patients undergoing the first permanent vascular access creation and followed the outcome of fistula until primary failure or success was assessed. Color duplex ultrasonography was used to measure the blood flow rate. Fistula blood flow rate was significantly smaller in elderly patients, however, it was >400 ml/min in over 78% of the elderly patients with successful fistulas. There was no difference in fistula blood flow rate between nondiabetics and diabetics. Dialysis adequacy (Kt/V) via fistula was the same between age groups and between diabetes mellitus status. Old age or diabetes per se did not significantly predispose a new fistula to primary failure, but concurrent old age and diabetes markedly increase the risk. In conclusion, a good primary outcome of newly created radiocephalic fistula and adequate dialysis via fistula were demonstrated for elderly and diabetic patients. However, the longevity of fistula in elderly and diabetic patients needs further study.

Hypertension and mineralocorticoid receptor activation cause cerebral parenchymal arteriole remodeling; this can limit cerebral perfusion and contribute to cognitive dysfunction. We utilized a mouse model of angiotensin II-induced hypertension to test the hypothesis that mineralocorticoid receptor activation impairs both TRPV4-mediated dilation of cerebral parenchymal arterioles and cognitive function. 16-18-week-old male C57bl/6 mice were treated with angiotensin II (800ng/kg/min) ± the mineralocorticoid receptor antagonist, eplerenone (100mg/kg/day) for 4 weeks; sham mice served as controls. Data are presented as mean ± SEM; n=5-14 per group. Eplerenone prevented the increased parenchymal arteriole myogenic tone and impaired carbachol-induced (10-10mol/L) dilation observed during hypertension. The carbachol-induced dilation was endothelium-derived hyperpolarization mediated because it could not be blocked by L-NAME (10mol/L) and indomethacin (10mol/L). We used GSK2193874 (10mol/L) to confirm that in all groups this dilation was dependent on TRPV4 activation. Dilation in response to the TRPV4 agonist GSK1016790A (10-10mol/L) was also reduced in the hypertensive mice and this defect was corrected by eplerenone. In the hypertensive and eplerenone treated animals, TRPV4 inhibition reduced myogenic tone, an effect that was not observed in arterioles from control animals. Eplerenone treatment also improved cognitive function and reduced microglia density in the hypertensive mice. These data suggest that the mineralocorticoid receptor is a potential therapeutic target to improve cerebrovascular function and cognition during hypertension.

No abstract

During continuous ambulatory peritoneal dialysis, the peritoneal mesothelial cell layer is under continuous sloughing and regeneration processes. Agents unfavorable for mesothelial cell growth may be harmful to the peritoneal membrane. We investigated whether frequent intraperitoneally instilled agents affect mesothelial cell growth. Peritoneal mesothelial cells were cultured from the human omentum. The proliferation was assessed by using a modified methyltetrazolium assay and confirmed by Coulter cell counting. The results showed that a high-glucose medium and heparin inhibited mesothelial cell growth. Cephalothin at the usual intraperitoneal loading and maintenance doses is toxic to mesothelial cells. Ceftazidime is toxic to mesothelial cells at its loading dose and inhibits growth at its maintenance dose. Aminoglycosides including netilmicin, gentamicin, and amikacin all had inhibitory effects at the loading and maintenance dose ranges. Vancomycin had no effect. The usual combinations of heparin and cephalothin with netilmicin or gentamicin as the initial treatment regimen for bacterial peritonitis are toxic to mesothelial cells. These results suggest that some intraperitoneal agents potentially may hamper mesothelial cell regeneration. The judicious use of heparin and the proper choice of antibiotic combinations may be warranted from the point of view of peritoneal protection.

SummaryWe report on a case of phaeochromocytoma whose initial presentation mimicked an acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation was used for the management of refractory cardiogenic shock and massive lung oedema. Suspicion and diagnosis of a phaeochromocytoma were made due to its unique clinical presentation during extracorporeal membrane oxygenation. Stabilisation of the crisis and recovery of cardiopulmonary function were achieved using the support of extracorporeal membrane oxygenation. This case highlights the difficulty in the differential diagnosis of cardiogenic shock secondary to phaeochromocytoma and the important role of extracorporeal membrane oxygenation can have in the successful resuscitation and management of these patients.

The effects of 150, 600 or 1,200 nmol/ml of nitrofurantoin on glutathione (GSH), glutathione disulfide (GSSG), protein thiols (PSH) and cell integrity were studied in the isolated perfused rat liver. Nitrofurantoin produced a dose-dependent, up to 3-fold, increase in bile flow and a marked, up to 150-fold, increase in biliary excretion of GSSG. By the conclusion of the experiment, tissue levels of GSH had fallen to 81 ± 14,41 ± 10 and 16 ± 5% of control values at the three dose levels. Tissue levels of GSSG rose from 18.3 ± 2.3 to 45.3 ± 8.0nmol/g and from 20.0 ± 6.0 to 187 ± 47 nmol/g within 15 min at the two higher doses, but fell to initial levels by the end of the experiment. Only at the 1,200-nmol/ml dose did the tissue levels of PSH decline, to 64 ± 14% of initial values, by the end of the experiment. Lactate dehydrogenase and transaminases were found in the perfusate only after the GSH and PSH levels had fallen. After a 60-min exposure to 1,200 nmol/ml of NFT followed by blank perfusate for 3 h, massive engorgement of the liver was noted. Microscopic examination revealed extensive interstitial edema, nuclear pyknosis, cytoplasmic shrinkage and vacuolization, and mitochondrial dense deposits. We conclude that toxic doses of nitrofurantoin can produce cellular depletion of GSH and PSH which, if not the direct cause, at least signal the loss of cell viability.

No abstract

Objective Hypertension‐associated PA dysfunction reduces cerebral perfusion and impairs cognition. This is associated with impaired TRPV4‐mediated PA dilation; therefore, we tested the hypothesis that TRPV4 channels are important regulators of cerebral perfusion, PA structure and dilation, and cognition. Methods Ten‐ to twelve‐month‐old male TRPV4 knockout (WKY‐Trpv4em4Mcwi) and age‐matched control WKY rats were studied. Cerebral perfusion was measured by MRI with arterial spin labeling. PA structure and function were assessed using pressure myography and cognitive function using the novel object recognition test. Results Cerebral perfusion was reduced in the WKY‐Trpv4em4Mcwi rats. This was not a result of PA remodeling because TRPV4 deletion did not change PA structure. TRPV4 deletion did not change PA myogenic tone development, but PAs from the WKY‐Trpv4em4Mcwi rats had severely blunted endothelium‐dependent dilation. The WKY‐Trpv4em4Mcwi rats had impaired cognitive function and exhibited depressive‐like behavior. The WKY‐Trpv4em4Mcwi rats also had increased microglia activation, and increased mRNA expression of GFAP and tumor necrosis factor alpha suggesting increased inflammation. Conclusion Our data indicate that TRPV4 channels play a critical role in cerebral perfusion, PA dilation, cognition, and inflammation. Impaired TRPV4 function in diseases such as hypertension may increase the risk of the development of vascular dementia.