The protective effect of cool dialysate is dependent on patients' predialysis temperature.

A significant proportion of hemodialysis patients have subnormal body temperature. Dialysis against cool dialysate has been frequently shown to reduce the incidence of symptomatic hypotension (SH), although only one of these reports included patient temperatures. Our hypothesis was that the response to cool or normal temperature dialysis could depend on a patient's baseline temperature. Of 128 patients in two hemodialysis units, 28 had a (mean of 5) baseline temperature less than 36 degrees C and 48 patients had a temperature higher than 36.5 degrees C. A crossover study was performed by dialyzing patients for 10 consecutive treatments with the same dialysate temperature, either 37 degrees C or 35 degrees C. All patients combined had a significant reduction in SH with 35 degrees C dialysate, 11.2% versus 5.5% with 37 degrees C dialysate (P = 0.001). The incidence of SH in euthermic patients was not affected by dialysate temperature. Hypothermic patients dialyzed against 37 degrees C dialysate had the highest incidence of SH, which decreased markedly with 35 degrees C dialysate (15.9% v 3.4%; P = 0.0001). There were no differences in age, duration of dialysis, gender, hemoglobin, urea, creatinine, or volume removed per dialysis between the two groups. In conclusion, subnormal temperature is common in dialysis patients but the etiology is unclear. The hemodynamic protective effect of cool dialysate only occurs in patients with subnormal temperatures. Only the subpopulation of patients with SH and low body temperature should be dialyzed against cool dialysate.

Familial nephropathic systemic amyloidosis caused by apolipoprotein AI variant Arg26.

A point mutation in the apolipoprotein AI (apoAI) gene causing autosomal dominant non-neuropathic systemic amyloidosis is described in a previously unreported Canadian family of British origin with five affected individuals in three generations. Amyloid deposits in the renal biopsy from the proband, a 31-year-old female presenting with hypertension and renal failure, stained immunospecifically with antiserum to apoAI. The plasma of all family members with amyloidosis contained both wild-type apoAI and a variant bearing one additional positive charge. Sequencing of the apoAI gene demonstrated that the proband was a heterozygote for a single base substitution in exon 3, changing codon 26 from GGC(Gly) to CGC(Arg). Concordance of the mutant allele with the presence of variant plasma apoAI and clinical features of amyloidosis was demonstrated. This is the third family in which this amyloidotic mutation has been described, but the distribution of amyloid deposits and their clinical effects are clearly determined by other genetic and/or environmental factors.

The cardiopulmonary and renal hemodynamic effects of norepinephrine in canine pulmonary embolism.

Autologous blood clot was injected into six dogs to produce a graduated decrease in cardiac output (CO). The effects of an infusion of norepinephrine, titrated to specific end points, were recorded before embolization and at two levels of pulmonary hypertension. Simultaneous measurements of systemic and renal hemodynamics were made. Sequential blood clot injection increased (p less than .01) pulmonary vascular resistance (PVR) from 1.3 to 13 to 33 mm Hg.L-1.min and reduced CO 45 percent and 75 percent (p less than .01). Norepinephrine increased both stroke volume and CO (p less than .01) in each condition and did not increase PVR. Since the biventricular filling pressures remained constant or fell slightly with norepinephrine, the increase in CO is best explained by an improvement in pump performance. There was no deterioration in renal blood flow or creatinine clearance with norepinephrine. The data suggested that in this model of right ventricular dysfunction, norepinephrine consistently improved myocardial performance without provoking further vasoconstriction in either the pulmonary or renal circulations.

Resting metabolic rate in lean and obese children: relationship to child and parent weight and percent-overweight change.

Two studies were conducted to assess differences in metabolic rate as a function of child weight (study I); and the interaction of child and parent weight (study II). In both studies obese children had higher resting metabolic rates (RMRs) than lean children (p less than 0.05). Child weight accounted for 72 and 78% of the variance in RMR in studies 1 and 2, respectively. Including parental weight did not improve the prediction of RMR. After 6 mo of treatment, obese children decreased percent overweight, whereas lean children showed no change (p less than 0.01). RMR in both groups remained unchanged after 6 mo. These results indicate that the RMR is higher in obese than in lean children, that changes in percent overweight that result from increases in height and no change in weight do not decrease RMR over 6 mo, and parent weight does not improve the prediction of child RMR.

Non-enzymatic glycation and altered renal structure and function in the diabetic rat.

Renal functional parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of non-enzymatic glycation of glomerular basement membrane were studied in rats rendered diabetic with streptozotocin. Diabetic animals had elevated, glycated hemoglobin levels (P less than 0.05), increased creatinine clearance, and urinary albumin excretion rates (P less than 0.05) as compared to insulin treated diabetic (euglycemic), age-matched, and streptozotocin non-diabetic animals. The level of non-enzymatic glycation of glomerular basement membrane was significantly elevated (P less than 0.05) in the diabetic animals as well, with the level of non-enzymatic glycation of all animals, correlating (P less than 0.05) to the average blood glucose level of each animal. Despite changes in functional parameters, and increased levels of non-enzymatic glycation between the diabetic and euglycemic animals, there was no difference in glomerular basement membrane thickness between the two groups. However, there was a difference between all diabetic euglycemics and the age-matched control animals. We hypothesize that increased glycation of glomerular basement membrane may alter renal function, possibly by affecting the net charge of the glomerular filtration barrier. However, glomerular basement membrane thickening per se does not affect the functional changes which have been observed, thus casting doubt upon its role in the development of diabetic nephropathy.

Effects of noradrenaline and isoproterenol on cardiopulmonary function in a canine model of acute pulmonary hypertension.

The authors investigated acute cardiopulmonary effects of noradrenaline and isoproterenol infusion in a canine model of increased pulmonary vascular resistance (PVR) and decreased cardiac output (CO). In six anesthetized, ventilated dogs, autologous blood clots were injected over approximately two hours to increase right ventricular (RV) afterload and decrease CO. After CO had decreased 40 percent dogs were treated with noradrenaline or isoproterenol in alternate sequence. Both drugs increased stroke volume but only isoproterenol affected CO. Flow increased from 1.3 to 3.0 L X min-1 (p less than .01) with isoproterenol infusion. Corresponding to the increase in CO, RV filling pressure and PVR decreased, from 9 to 5 mm Hg, and from 36 to 16 mm Hg X L-1 X min (p less than .01) respectively. When a moderate decrease in CO complicates an acute increase in PVR, isoproterenol may be an excellent drug to treat the decrease in flow.

Effect of diet and controlled exercise on weight loss in obese children.

The effects of adding exercise to diet for weight control in obese children were evaluated by randomizing obese girls to one of two groups: diet and diet plus exercise. During the first 6 weeks of the treatment, children exercised in a supervised three times a week exercise program, in which they walked or ran 3 miles. Significant decreases from baseline weight and in percent overweight were observed for both groups during the year of treatment. Significant decreases in percent overweight were observed at 0 to 2 months and then at 2 to 6 months for the children who were exercising, whereas percent overweight in children in the diet-alone group decreased only from 0 to 2 months. In addition, a significant improvement in fitness was observed only for children in the diet plus exercise group.

Pharmacokinetics of metronidazole in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of metronidazole, its biologically active alcohol metabolite, and its inactive acid metabolite were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis and five patients undergoing hemodialysis. The latter were studied on off-dialysis days as a control group. Peritoneal dialysis caused insignificant changes in the apparent volume of distribution, elimination half-life, and total body clearance of metronidazole. Peritoneal dialysis clearance (4.49 +/- 0.88 ml/kg per h [mean +/- standard deviation]) accounted for only 8.9% of total body clearance (50.17 +/- 18.64 ml/kg per h). Analysis of the 24-h area under the serum concentration versus time curves and peritoneal dialysis clearance data for the two metabolites suggested a similar insignificant effect of peritoneal dialysis on their elimination. Metronidazole dialysate concentrations in the first 6-h exchange ranged from 7.6 to 11.7 micrograms/ml. This would suggest that cumulative penetration of metronidazole from the systemic circulation into the peritoneal cavity with dosing every 8 h should lead to adequate concentrations for the treatment of anaerobic peritonitis. For the treatment of systemic anaerobic infections, it would appear at present that metronidazole dosage adjustments are not necessary in patients undergoing continuous ambulatory peritoneal dialysis. The potential for metabolite accumulation was noted in this study. If further studies confirm that excessive serum metabolite concentrations are toxic, dosage reduction in this group of patients may be warranted.