The influence of autonomic neuropathy on hypotension during hemodialysis

Many patients with chronic renal failure experience profound hypotension during hemodialysis. This phenomenon may be caused by hypovolemia, autonomic or cardiac dysfunction, vascular resistance defects or vasoactive substances such as nitric oxide or adrenomedullin. The aim of the study was to evaluate the influence of autonomic neuropathy on the occurrence of hypotension during hemodialysis. Fifty-three patients with chronic renal failure on maintenance hemodialysis underwent a standard battery of cardiovascular tests for the diagnosis of autonomic neuropathy. The study population was then divided into two groups, with (AN+) and without (AN−) autonomic neuropathy. Blood pressure (BP) was recorded before, during and after hemodialysis for 10 consecutive dialysis sessions and the mean value was calculated. Results Of the patients, 38 % were AN+. During hemodialysis, systolic BP was lower in AN+ than in AN− patients at the third hour (110.0 ± 17.5 vs 128.0 ± 26.2; p = 0.049). Systolic BP reduction during hemodialysis was greater in AN+ than AN− patients (−21.2 ± 10.9 vs −13.5 ± 10.6 % change, p = 0.013). Conclusion The presence of autonomic neuropathy is associated with a more severe BP fall during hemodialysis. Routine evaluation of autonomic function may be helpful in defining patients at risk for dialysis-induced hypotension. Received: 14 September 2001, Accepted: 19 February 2002     

Efficient surface expression of platelet GPIIb-IIIa requires both subunits

Platelet membrane GPIIb-IIIa is a member of the integrin family of heterodimeric adhesion receptors. Processing and export of certain leukocyte and melanoma integrins is disrupted in cells lacking one subunit. We found that surface expression of GPIIb-IIIa, measured by fluorescent activated cell sorting or by surface labeling, required cotransfection of both subunits. In contrast, surface expression was not detected when the subunits were transfected individually. Immunoprecipitation of metabolically labeled transfected cells confirmed the presence of comparable levels of intracellular protein in all cases. When both subunits were transfected, post-translational cleavage of Pro-GPIIb to yield GPIIb heavy chain was also seen, while transfection with GPIIb alone resulted in coprecipitation of Pro-GPIIb with a second band that may be an endogenous beta subunit. Pro-GPIIb in these transfectants was not processed to yield GPIIb heavy chain. When transfected into COS cells alone, transiently expressed GPIIIa remained intracellular and did not appear to complex with any endogenous proteins. Thus, surface expression of processed GPIIb-IIIa depends on the presence of both subunits; the coordinate reduction of both subunits observed in some cases of Glanzmann's thrombasthenia may result from mutation affecting only one.     

A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.     

The impact of blood transfusion on the occurrence of pneumonitis in primary cytomegalovirus infection after liver transplantation

The influence of blood transfusion, and particularly the transfusion of blood from cytomegalovirus (CMV)-seropositive donors, on the incidence of primary CMV infection following liver transplantation was studied prospectively in 29 consecutive CMV-seronegative adult liver transplant recipients. Fourteen patients received a liver graft from a CMV- seropositive donor (Group A), whereas for 15 patients, the donor was CMV seronegative (Group B). Eleven patients (79%) in Group A but only two (13%) in Group B developed CMV infection (odds ratio, 23.8; 95% confidence interval, 3.5-169.4). In five Group A patients, primary CMV infection resulted in pneumonitis. There was no statistical difference in the total number of blood units and the number of units of CMV- seropositive blood given to patients who did or did not develop CMV infection in both Groups A and B (odds ratio for unit of CMV- seropositive blood transfused, 1.07; 95% confidence interval, 0.96- 1.19). However, Group A patients who developed CMV pneumonitis received a higher total number of blood units (median, 44) and of CMV- seropositive blood units (median, 18) than did patients who developed other CMV infections (asymptomatic CMV, CMV syndrome, or CMV hepatitis), who received a median of 9 total units of blood and 5 units of CMV-seropositive blood (p = 0.004). It is concluded that the total number of blood units and of CMV-seropositive blood units transfused does not have an effect on the incidence of primary CMV infection after liver transplantation, but it does have an impact on the severity of the infection in recipients of a CMV-seropositive allograft.