Biomedical subjects
Publications and source records attributed to R A Ward.
The splenectomnized juvenile gibbon, Hylobates lar, is susceptible to infection with trophozoites of Plasmodium falciparum. All subjects in a group of six animals that were injected with freshly collected blood from four infected humans in Saraburi Province, Thailand, developed parasitemia 2 to 20 days later; infections were transmitted from one of these subjects to three clean gibbons.
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United States standards for the microbiologic quality of dialysate are not very stringent and have remained unchanged for more than 20 years, despite significant changes in the patient population and in the technology of hemodialysis. Numerous studies have demonstrated that bacterial products can cross dialysis membranes and stimulate an inflammatory response in the patient. Inflammation has been implicated in several complications associated with long-term hemodialysis therapy, and the use of ultrapure dialysate has been shown to reduce the incidence of one of these complications, beta2-microglobulin amyloidosis. Since technological innovations in water treatment and improvements in dialysis machine design allow the routine production of ultrapure dialysate, its use should now become standard.
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We created an experimental model to evaluate the effects of strain rate on the mechanism of combined cruciate ligament injuries in knee hyperextension. Using straight knee hyperextension to rupture the anterior and posterior cruciates, two strain rates (approximately 100% per second and 5400% per second) were applied to reproduce two clinical injury patterns of the knee: low energy (sporting) and high energy (pedestrian-motor vehicle accident). Ten pairs of fresh-frozen cadaveric knees were injured to 45 degrees of hyperextension. Strain rate sensitivity of the posterior cruciate ligament was shown in this model, with midsubstance tears occuring in specimens tested at a low rate and avulsion "stripping" injuries from the femoral side occuring at a high rate. A variable pattern of anterior cruciate ligament tears at both high and low rates suggests that the specific injury mechanism may also involve other factors including notch morphology. We present a simplified mathematic model used to estimate posterior cruciate ligament strain during knee hyperextension.
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Modern age stratification has contributed to greater differentiation of old age from the rest of the life cycle and lowered status for the aged. Discontinuity in the transition to old age makes the use of time a central issue, but psychological constriction displayed by many older people results from failure to facilitate creative personal expression through the life cycle and constraints on the options available and considered appropriate for the aged. Pressures for change in these options may come from cohort change in the characteristics of future older people and emerging postindustrial values.
The ability of DEAE-cellulose (Hemophan) membranes to bind heparin may reduce bioavailable heparin and predispose to dialyzer clotting, thus preventing use of Hemophan with low-dose heparin. To examine this possibility, residual blood volumes were determined following 95 treatments with dialyzers containing Hemophan membranes in 11 patients. No heparin was added to the saline used to prime the dialyzers. The anticoagulant effect of heparin was measured using recalcified activated clotting times (RACT). Two heparin doses, calculated by a pharmacokinetic model to increase baseline RACT by 12.5% and 25%, were used for each patient. The mean heparin loading doses were 10.2 +/- 2.8 and 15.3 +/- 2.2 IU/kg, respectively, and the mean infusion rates were 11.1 +/- 3.2 and 14.7 +/- 3.2 IU/kg/h, respectively. Residual blood volumes were determined by red cell lysis and hemoglobinometry. In 88 treatments, residual blood volume averaged 1.6 +/- 1.5 ml. In the other seven treatments, residual blood volume greater than 10 ml was seen. In five of these cases, clotting appeared to propagate from the arterial drip chamber. Residual blood volume did not correlate with the level of heparin. The data show that low-dose heparin can be used with Hemophan membranes, and suggest that blood tubing design may be an important factor in blood circuit clotting during hemodialysis.
Membranes prepared from hydrophobic synthetic polymers adsorb proteins. Alloying these polymers with hydrophilic polymers increases water wetability and reduces hydrophobic interactions. The authors tested the hypothesis that alloying could affect the biocompatibility of the resultant membrane. Polymer films were cast from solutions containing 12% polysulfone and 4, 8, or 12% polyvinylpyrrolidone in dimethylacetamide. The effect of the films on the complement system and neutrophil function was assessed by incubating them in normal plasma and whole blood at 37 degrees C. Complement activation was followed by measuring plasma concentrations of C3a des Arg and C5a des Arg. Flow cytometric measurements of phagocytic capacity, H2O2 production, and expression of the C3bi receptor were used to assess neutrophil function. The degree of complement activation was found to depend on the composition of the polymer film. C3a des Arg and C5a des Arg generation decreased 75% and 86%, respectively, as the polyvinylpyrolidone content of the casting solution was increased from 25 to 50%. This was accompanied by a decrease in stimulation of neutrophil H2O2 production and C3bi receptor expression. From these data, the authors conclude that alloying with polyvinylpyrrolidone can affect the biocompatibility of polysulfone.
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Tumor necrosis factor-alpha (TNF alpha) interacts with cells through specific membrane receptors. Exposure to agonists, such as C5a, causes cells to shed these receptors, forming soluble TNF alpha binding proteins (sTNFR). Because cellulose membranes activate complement, we tested the hypothesis that dialysis with these membranes contributes to the increased levels of sTNFR observed in hemodialysis patients. sTNFR levels were measured pre- and post-dialysis in patients treated with dialyzers containing new cellulose membranes. Plasma sTNFR concentrations were markedly increased pre-dialysis, compared with normal (38.3 +/- 13.5 ng/ml versus 2.1 +/- 0.7 ng/ml), and increased further during dialysis, even after post-dialysis concentrations were corrected for hemoconcentration. We examined the impact of the increased sTNFR levels on the ability of TNF alpha to prime neutrophil superoxide production in cross-incubation experiments. When normal neutrophils were incubated with TNF alpha in the presence of hemodialysis patient plasma, the resulting increase in fMLP stimulated superoxide production was significantly less than when normal plasma was used. Incubation of hemodialysis patient neutrophils in normal plasma only partly restored their ability to be primed by TNF alpha, suggesting an intrinsic functional defect in these cells, in addition to the effects of sTNFR. Our results suggest that dialysis with cellulose membranes contributes to the increased levels of sTNFR observed in dialysis patients, and that these concentrations are sufficient to impair the normal actions of TNF alpha.