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Biomedical subjects

G Carter

Publications and source records attributed to G Carter.

107 records · Page 6Linked to original sources
PubMed1981

Phenobarbital and phenytoin in neonatal seizures: metabolism and tissue distribution.

Loading doses of 15 to 20 mg per kilogram of both phenobarbital and phenytoin, administered intravenously, are necessary in the newborn to achieve rapid therapeutic plasma anticonvulsant levels. Maintenance doses of 3 to 4 mg per kilogram of both agents will maintain therapeutic levels. Phenytoin is, however, not predictably absorbed by the oral route. Brain:plasma ratios were 0.71 +/- 0.21 for phenobarbital and 1.28 +/- 0.32 for phenytoin, which are in general agreement with reported adult values. The brain:plasma ratio of phenobarbital increased with gestational age. Phenytoin was found in higher concentration in gray matter, whereas phenobarbital was equally distributed between gray and white matter.

Brain↗
PubMed1978

Detection of ovulation by a method of change in finger-finger electropotential readings.

The purpose of this study was to determine whether ovulation can be detected by using a device (OvultronR) that measures electropotential differences in finger-to-finger contact. Daily basal body temperatures and five consecutive readings on the OvultronR were obtained each morning in 34 women for a three-month period. During one cycle an endometrial biopsy was taken and dated to document the time of ovulation. Our results showed that in only five out of 104 cycles did the device show an isolated change at the time of ovulation. This device is not a reliable method either for prediction of or the detection of ovulation. Therefore, one cannot effectively use this device alone as a basis for a rhythm method of contraception.

Adult↗
PubMed1976

Computer simulation of leukemia therapy: combined pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside.

An integrated mathematic computer-based model of the pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside (ara-C) is described. The compartment model of Bischoff and Dedrick is extended to the intracellular level by inclusion of equations describing the phosphorylation, dephosphorylation, and deamination of ara-C with enzymatic feedback control. The activities of kinase, deaminase, and phosphatase are explicitly included in the models and are estimated from relevant data. Cell proliferation is described by a continuous-flow mathematic model in which cellular maturation and cell-to-cell variability in maturation rates are key variables. Cell proliferation is related to intracellular biochemistry through mathematic expressions which relate cell lethality and progression delay to the time course of intracellular ara-CTP. In vitro and in vivo experiments performed in a number of laboratories are compared by simulation. The most sensitive parameters in dose-response and cell-survival simulations are deoxycytidine kinase activity, ara-CTP half-life, renal clearance of ara-C, and cell-kinetic parameters for proliferation and cell killing. Progression delay is vital to the realistic simulation of divided-dose schedules. By comparative simulation we have identified areas of uncertainty which can be classified by a few additional measurements. The applications of simulations combining pharmacokinetic, biochemical, and cell-kinetic data in vitro and in vivo are discussed, exploring consistency among different measurements, and relating experimental protocols to clinical treatment.

Animals↗
PubMedDate not supplied

Morphological changes in endocardium subjected to global ischaemia.

To provide insight into the effects of severe ischaemia on endocardium, the sequence of morphological changes which develop in the endocardium of the isolated rat heart subjected to 0-12 hours of global ischaemia at 37 degrees C was examined. A progression of changes occurred. Following one or more hours of ischaemia crater-like depressions and blebs appeared on the luminal surfaces of ventricular endothelial cells, with margination and clumping of nuclear chromatin, loss of glycogen granules, swelling of mitochondria, and the development of subendothelial membrane-bound dilatations of myocytes. Following two or more hours of ischaemia there was progressive separation of endothelial cells along their intercellular boundaries and desquamation of an increasing proportion of these cells. In regions of desquamation the surface was initially smooth due to persistence of the lamina densa of the basal lamina, but after longer periods of ischaemia the surface became rough with exposure first of the subendothelial connective tissue fibres (4 hours) and eventually of cardiac muscle cells (12 hours).

Animals↗
PubMedDate not supplied

The evolution of air transport systems: a pictorial review.

The air transport of patients began over seventy years ago in primitive biplanes. The ability to fly over the obstacles of the battlefield created enthusiasm in both the military and the medical communities. With the advent of vertical flight, the need for conventional runways was obviated allowing for casualties to be transported directly from the site of injury. After their introduction as air ambulances in 1945, helicopters soon supplanted ground ambulances with their speed and versatility. By the mid-1960s, civilian casualties were being transported by helicopter as regional trauma care developed in the United States. Today aeromedical programs continue to expand rapidly, even as closer scrutiny of their efficacy, cost, and safety are explored. A pictorial review highlighting the evolution of air transport systems is presented.

Aircraft↗
PubMedDate not supplied

Specific pancreatic enzymes activate macrophages to produce tumor necrosis factor-alpha: role of nuclear factor kappa B and inhibitory kappa B proteins.

The triggering events by which mononuclear cells throughout the body are induced to produce large amounts of cytokines during acute pancreatitis are unclear. However, recent work in our laboratory demonstrated that three specific pancreatic enzymes (elastase, carboxypeptidase A, and lipase) induced dramatic tumor necrosis factor-alpha (TNF-alpha) protein production from macrophages, whereas all others could not. This series of experiments was designed to examine the second messenger system by which this occurs. The rat macrophage cell line NR8383 was incubated for 3 hours with elastase, carboxypeptidase A, lipase, trypsin, or lipopolysaccharide (positive control). Activation of nuclear factor kappa B (NF-kappa B) was demonstrated by electrophoretic mobility shift assay, presence of inhibitory kappa B alpha and beta (I kappa B-alpha and I kappa B-beta) by Western blot analysis, and TNF-alpha protein production by enzyme-linked immunosorbent assay. Elastase, carboxypeptidase A, and lipase induced degradation of I kappa B-beta (but not I kappa B-alpha), activation of NF-kappa B, and production of TNF-alpha protein, whereas inhibition of I kappa B with pyrrolidine dithiocarbamate attenuated this response. Trypsin was unable to elicit any of these responses. Macrophages can be induced by specific activated pancreatic enzymes-elastase, carboxypeptidase A, and lipase-to produce TNF-alpha. This process is dependent on I kappa B-beta degradation and NF- kappa B activation, suggesting that these enzymes trigger this second messenger system through specific membrane-bound receptors.

Acute Disease↗
PubMedDate not supplied

Cationic liposome-mediated gene transfer during acute pancreatitis: tissue specificity, duration, and effects of acute inflammation.

Production of inflammatory cytokines in the pancreas, lung, and liver is believed to play a major role in the development of severe pancreatitis. This tissue-specific production could lend itself to directed anti-cytokine gene therapy if an appropriate delivery system could be developed. This study was undertaken to examine a novel approach for the delivery of protein-based therapies to the tissues involved during acute pancreatitis. Healthy mice received an intraperitoneal injection of cationic liposomes and a DNA plasmid containing the chloramphenicol acetyltransferase (CAT) reporter gene. Animals were killed at 12 hours and 1, 2, 3, 7, and 14 days with serum, pancreas, lung, and liver harvested. Acute pancreatitis was induced (cerulein, 50 micrograms/kg/hr intraperitoneally x4) in additional mice before or after CAT transfection. The presence of pancreatitis was established in all animals by histologic scoring of pancreata and by serum amylase and lipase levels. CAT transfection efficiency was determined by quantitative CAT enzyme activity within tissue homogenates. Animals that received the liposome were successfully transfected with the CAT gene into the pancreas, lungs, and liver. Maximal transfection in each tissue occurred at 12 hours with decreasing CAT activity over the ensuing 14 days. No healthy animals receiving the CAT gene developed elevations in amylase, lipase, or any histologic parameter of pancreatitis. Transfection efficiency in the pancreas was markedly increased by preexisting or delayed induction of pancreatitis, whereas transfection of the lung and liver was increased to a lesser extent. Gene transfection into the pancreas, liver, and lungs is possible using a cationic liposome delivery system that does not induce pancreatitis or pancreatic inflammation. Pancreatic expression of the gene product is equal to or greater than that of the organs of the reticuloendothelial system and continues at very high efficiency rates during acute pancreatitis.

Acute Disease↗