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Biomedical subjects

G S Moss

Publications and source records attributed to G S Moss.

156 records · Page 9Linked to original sources
PubMedDate not supplied

Clinical development of human polymerized hemoglobin as a blood substitute.

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelium-derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are under way to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers and are now under way to assess the safety and efficacy of Poly SFH-P as a clinically useful red blood cell substitute for treatment of acute blood loss in the setting of trauma and surgery.

Animals↗
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Preparation and in vitro characteristics of polymerized pyridoxylated hemoglobin.

Stroma-free hemoglobin solutions have been the subject of extensive studies as potential acellular oxygen carriers. Oncotic pressure considerations limit the hemoglobin concentration of the solutions (6-8 g/dl) to one-half the normal whole blood values. Furthermore, the free hemoglobin has a short plasma half-life (2-4 hours). In principle, polymerization offers a means of normalizing the oxygen-carrying capacity as well as extending the plasma half-life. Pyridoxylation of hemoglobin prior to polymerization provides an acceptable P50. Pyridoxylated hemoglobin (14-16 g/dl) was polymerized with a 12.5 percent glutaraldehyde solution. Since the goal was to obtain a 15 g per dl solution iso-oncotic with plasma, the polymerization reaction was monitored by the drop in colloid osmotic pressure. The reaction was quenched with 1.3 M lysine when the colloid osmotic pressure reached normal values (20-25 torr). The polymerization yield was 80 percent, with molecular weights ranging from 120,000 to 600,000 Dalton. The polymerized hemoglobin had a binding coefficient of 1.32, a P50 of 16 torr, a Bohr coefficient of -0.12, and a Hill coefficient of 1.7. The viscosity of the solution was 4.5 centipoise. The methemoglobin levels were comparable to that of unpolymerized stroma-free hemoglobin. Polymerized hemoglobin solutions provide a normal oxygen-carrying capacity with a P50 comparable to that of unpolymerized stroma-free hemoglobin solutions.

Blood Substitutes↗
PubMedDate not supplied

Effect of commercially available chemically defined liquid diets on the intestinal microflora and bacterial translocation from the gut.

The effect of chemically defined liquid diets on the intestinal microflora and bacterial translocation from the gut was studied in the rat. Seventy-five female Fischer rats were randomized to five groups of 15 animals each. Group I was fed rat chow and water, group II was fed Vivonex TEN, group III was fed Ensure, group IV was fed Enrich, and group V was fed Ensure plus ground corn cobs, a crude fiber source. Animals were fed their respective diets ad libitum for 1 week and then killed. Quantitative culture of the mesenteric lymph nodes (MLN) and cecum was performed to determine bacterial translocation from the gut. A 66% translocation rate (10/15) of bacteria to MLN was observed in the animals fed Ensure and Enrich compared to 21% in the Vivonex TEN group (3/14) and 20% in the animals fed Ensure plus ground corn cobs (3/15). None of the animals in the control group eating their normal diets of rat chow and water developed positive MLN. Statistical significance (p less than 0.001) was achieved between the Ensure and Enrich groups when compared to controls but not between the Vivonex TEN and Ensure plus corn cobs. Cecal culture revealed a statistically significant rise in cecal bacteria in all groups when compared to the control group (group I). These results indicate that chemically defined liquid diets result in altered intestinal microflora and bacterial translocation from the gut.

Animals↗