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Biomedical subjects

G Bynum

Publications and source records attributed to G Bynum.

6 recordsLinked to original sources

Cellular replication and aging.

Controversy exists concerning the effect of aging on replicating cell systems. This review summarizes a number of studies which indicate that both in vivo and in vitro, cell replication is significantly altered during aging. In vitro, studies of both human lymphocytes and fibroblasts indicated that a number of replication kinetic parameters are influenced by the age of the cell donor. In vivo, the application of the bromodeoxyuridine-(BrdU)-differential chromatid staining techniques to the analysis of cellular replication kinetics has permitted us to demonstrate that cellular replication is also significantly diminished with aging in mouse and rat cell populations. Therefore, both in vivo and in vitro in human as well as rodent cell populations, the rates of cellular replication are significantly decreased with cellular aging.

Aging

Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy.

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.

Adolescent

Increased survival in experimental dog heatstroke after reduction of gut flora.

A study was undertaken to determine if gut flora contribute to the pathophysiology of experimental canine heatstroke. Fifty animals in four groups were anesthetized with sodium pentobarbital (25 mg/kg) intravenously. An air temperature of 42-46 degrees C was maintained adjacent to the dog with a water-heated blanket for approximately 2 h until rectal temperatures rose to 43.5 +/- 0.4 degrees C. Animals were then cooled passively in room air (28 degrees C, 20% RH) until death or until 18 h elapsed, and were euthanized. Reduction of intestine stool and bacterial contents with antibiotics, cathartics, and enemas prior to heatstroke increased the incidence of 18-h survival from 20.0% to 70.6%; antibiotics administered after heatstroke did not alter the incidence of survival over control values. These data suggest that gut flora, presumably through endotoxemia, contribute to the evolution of heatstroke pathophysiology.

Animals

Peritoneal lavage cooling in an anesthetized dog heatstroke model.

This study was undertaken to compare cooling in room air (27 degrees C, 20% RH), ice slush surface cooling, and peritoneal lavage cooling (6-10 degrees C) as methods for lowering body temperature in an anesthetized dog heatstroke model. We anesthetized 19 animals with sodium pentobarbital (25 mg/kg) intravenously, and maintained them in an ambient temperature of 42-46 degrees C with a water heating blanket approximately 2.0 h until rectal temperatures rose to 43.2 +/- 0.2 degrees C. At the maximum rectal temperature, the heating blankets were removed, and animals were cooled, observed until death occurred or 18 h elapsed, and then sacrificed. The data demonstrate that maximum cooling rates of rectal temperature were: peritoneal lavage, 0.56 degrees C/min; ice slush, 0.11 degrees C/min; and 27 degrees C air cooling, 0.06 degrees C/min. The incidence of 18-h survival for lavage-cooled dogs when supported with normothermic dialysis every 4 h was significantly greater than for either ice slush or air cooled dogs.

Animals

An anesthetized dog heatstroke model.

This study was undertaken to develop an anesthetized dog heatstroke model. Forty-six animals were anesthetized with pentobarbital sodium (25 mg/kg) intravenously, and maintained at an ambient temperature of (42-46 degrees C) with a water-heated blanket over 2.5-3.0 h until rectal temperatures rose to 43.0-44.5 degrees C. Animals then cooled passively until death occurred or until 18 h elapsed, and were prepared for autopsy. Liver, kidney, and brain temperature, mean weighted skin temperature, mean weighted surface heat loss, and metabolic rates were obtained. There were no significant differences between liver, kidney, brain, and rectal temperatures during the heating and cooling periods. Cardiac output rose to 127% of initial value, and dropped rapidly to zero at 43.4 degrees C rectal temperature. The rapid decline was accompanied by a doubling of heart rate and a rapid drop in blood pressure and respiratory rate. Cheyne-Stokes respiration and apnea preceded bradycardia followed by asystole or ventricular fibrillation. Certain serum constituents demonstrated modest elevations suggestive of widespread tissue damage. Autopsy did not reveal a clear pattern of heat injury, with the exception of consistent congestion of the major organs and karyorrhexis of lymphocytes. These data are in agreement with similar data from human heatstroke victims and other heatstroke modeling in dogs, and support the concept that the anesthetized dog can in many respects provide an adequate model for human heatstroke.

Anesthesia, Intravenous

Recurrent heat exposure: effects on levels of plasma and urinary sodium and potassium in resting and exercising men.

Heat acclimatization was induced in a group of healthy young men by walking on a treadmill (5.6 km/h, 49 degrees C/27 degrees C dry/wet bulb, 90 min/day, 7 d) and confirmed by observing significantly reduced final rectal temperatures and heart rates on the seventh day of exercise in the heat. A second group of men, paired for maximal oxygen consumption and body weight, remained sedentary under identical environmental conditions. While the mild exercise combined with the severe heat conditions induced significant hyperkalemia (p less than 0.02, minimal significance) on both the first and final days, there did occur an attenuated response with significantly (p less than 0.01) reduced plasma K+ after 45 min on the seventh day when compared with first day levels. No significant inter- or intragroup differences in plasma Na+ content of 24-h urine samples showed that men exercising in the heat retained an increased ability to conserve Na+, while sedentary individuals consistently displayed increased excretion of Na+. Thus, we concluded that even the mild exercise described herein effected hyperkalemia at each sampling time, but the level of hyperkalemia was attenuated after acclimatization, and while Na+ was conserved in the exercising men, no such adaptive processes occurred in sedentary individuals.

Acclimatization