Biomedical subjects
Publications and source records attributed to C J Hull.
The effects of age on the pharmacokinetics of pancuronium were investigated. The distribution volume of pancuronium did not appear to be age-dependent, but elimination of the drug decreased with increasing age. The clinical implications of these findings are discussed.
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Antibodies to group A streptococcal carbohydrate, demonstrable by radioimmunoassay, were elicited in Pacific hagfish, Eptatretus stoutii, after prolonged immunization with whole cell vaccine. This hagfish antibody, isolated by ion-exchange chromatography of immune serum, exhibited a single precipitin line after immunoelectrophoresis against rabbit antiserum to hagfish serum. The isolated antibodies retained high binding activity for the streptococcal carbohydrate, but lacked the natural hemagglutinating activity found in both nonimmune and immune sera. Analysis by gel filtration in neutral and dissociating buffers and by sodium dodecyl sulfate/polyacrylamide gel electrophoresis under nonreducing conditions indicated an intact molecule of molecular weight approximately 160,000 that may be noncovalently associated in a polymer of higher molecular weight. Heavy chains of mobility identical to that of murine mu chains and light chains of mobility significantly slower than murine lambda chains were obtained after sodium dodecyl sulfate gel electrophoresis under reducing conditions. Instability of the tertiary structure of the antibody molecule was indicated by partial dissociation in buffers containing sodium dodecyl sulfate and by dissociation at low concentrations of reducing agent. In contrast to its well-developed system of cell-mediated immunity, only a minimal system of circulating antibody production is evident in this primitive fish. No evidence for divergence of cyclostome lymphocytes into separate T- and B-cell systems has yet been discerned.
It has been demonstrated that a simple two-compartment kinetic model may account for the changes in plasma concentration of pancuronium after i.v. administration. However, it can be shown that this simple model does not account satisfactory for the observed changes in muscle twitch response. By the addition of a receptor (biophase) compartment, twitch response can be reconciled with model behavior and the characteristics resemble those predicted by animal studies. The complete model is applied to the problem of total renal failure, and shows that patients with this condition are likely to be marginally resistant to small doses of pancuronium, with a normal rate of recovery. However, larger doses are likely to result in delayed recovery, the duration of effect increasing in a dose-dependent manner.
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Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.
After i.v. administration, the distribution and elimination of many drugs may be simulated by a compartmental mathematical model. The analogue can be used to construct such models in electrical terms. When programmed with an appropriate model, the analogue can be used in a wide range of predictive studies. The application of the analogue is illustrated by analysis of serial plasma concentrations of fentanyl and pancuronium.
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