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Biomedical subjects

G Kent

Publications and source records attributed to G Kent.

At least 109 records · Page 6Linked to original sources

Neutrophil circulation and release from bone marrow during hypothermia.

The effect of hypothermia on neutrophil circulation and release from bone marrow has been studied. Pigs were anesthetized and maintained at 37 degrees C or surface cooled to 29 degrees C over 60 min. As the core temperature was reduced to 29 degrees C, the number of circulating neutrophils (X 10(9) per liter) fell from 6.0 +/- 0.6 to 2.3 +/- 0.3 by 60 min. No significant change in the number of circulating mature or immature neutrophils was observed over the 4 h of observation at 29 degrees C. Neutrophil demargination after administration of intravenous catecholamines was similar at 37 and 29 degrees C. Steroid stimulation of bone marrow to release neutrophils was markedly impaired at 29 degrees C. Circulating mature neutrophils in normothermic pigs increased from 5.6 +/- 1.2 to 10.4 +/- 1.2 by 120 min after administration of intravenous hydrocortisone sodium succinate. Circulating immature neutrophils increased from 1.7 +/- 0.3 to 5.3 +/- 0.4. At 29 degrees C, no significant changes in the number of circulating mature or immature neutrophils occurred. Endotoxin also failed to stimulate neutrophil release from the bone marrow. Furthermore, a marked neutropenia occurred in hypothermic pigs after intravenous endotoxin, which persisted for the 3 h of observation. Neutrophil circulation and release from bone marrow are compromised by hypothermia, which may increase the risk for bacterial infection.

Animals↗

Treatment of ovine cretinism in utero with 3,5-dimethyl-3'-isopropyl-L-thyronine.

Placental transfer of iodothyronines is minimal in most species. The nonhalogenated thyroid hormone analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) was administered to pregnant ewes to determine if this compound could prevent cretinism in the thyroidectomized fetal lamb. Pharmacokinetic studies comparing [125I]T3 and [3H]DIMIT resulted in fetal-maternal ratios for [3H]DIMIT which were 5- to 10-fold higher than the ratios for [125I]T3, suggestive of preferential transport of DIMIT across the placenta. Subsequently, DIMIT was administered to three pregnant ewes after hysterotomy and fetal thyroidectomy at 95-98 days gestation. Intramuscular DIMIT (1200-2000 micrograms/day) caused suppression of maternal T4 concentrations from a mean of 4.9 micrograms/dl before hysterotomy to less than 1 micrograms/dl within 1-2 weeks. All three thyroidectomized lambs had clinical signs of cretinism at birth and died. Skeletal and lung maturation were delayed in these animals, all of whom had undetectable serum T4 concentrations. In contrast to DIMIT's proven thyromimetic activity in other fetal animal models, this thyroid hormone analog failed to prevent cretinism in thyroidectomized fetal lambs even when administered to the ewe at a dose that suppressed maternal thyroid function.

Animals↗

Oxygenation during high-frequency ventilation compared with conventional mechanical ventilation in two models of lung injury.

Oxygenation and mean lung volume were investigated during high frequency oscillation (HFO) and conventional mechanical ventilation (CMV) in two models of lung disease and related to the lung mechanics of the lesions. Oleic acid (n = 10) or lung lavage (n = 12) pulmonary injury was induced in a series of rabbits. Each animal was alternately ventilated with HFO (15 Hz sinusoidal wave form) and CMV (flow generator I:E, 1:2; f, 30 breaths/min; VT, 10 to 15 ml/kg) at matched mean airway pressure. Pao2 was measured 5 minutes after onset of ventilation. In the lung lavage model Pao2 was significantly greater during HFO than CMV (Pao2 228 +/- 116 torr vs 71 +/- 42 torr) provided that mean airway pressure was greater than the distinct opening pressure characteristic of this lesion. In the oleic acid model oxygenation was again superior during HFO (Pao2 269 +/- 116 torr vs 110 +/- 83 torr), but only if HFO was preceded by a sustained inflation. Plethysmography in a subset of six rabbits from each group revealed that the improvements in oxygenation were associated with significantly higher mean lung volumes during HFO than CMV (58 +/- 30 ml vs 29 +/- 14 ml lung lavage model, 45 +/- 15 ml vs 30.9 +/- 13 ml on the oleic acid model). The importance of a sustained inflation in rapidly optimizing gas exchange during HFO but not CMV was demonstrated. A sustained inflation resulted in immediate and sustained increases in Pao2 (from 134 +/- 102 torr to 274 +/0 124 torr in the oleic acid model; from 115 +/- 105 torr to 291 +/- 143 torr in the lung lavage model) and mean lung volume (41.8 +/- 11 to 53.8 +/- 9.7 ml in the oleic acid model, 30.9 +/- 7.7 ml to 42.8 +/- 5 ml in the lung lavage model). It is suggested that in these two particular models of lung disease, HFO, when combined with a sustained inflation (to provide opening forces), can more fully exploit the pressure volume hysteresis of unstable lung units than CMV, thereby resulting in the larger mean lung volumes and better oxygenation observed during HFO.

Animals↗

Clofibrate and vascular smooth muscle: actions on rabbit aorta preparations.

Clofibrate (Atromid-S) has been found to inhibit the contractility of isolated rabbit aortic muscle rings produced by exposure to either norepinephrine, histamine or angiotensin. The inhibitory effect of clofibrate is seen optimally in Krebs medium containing low, 5 X 10-5 M, calcium but is not found in medium containing 2.5 X 10-3 M calcium. In contrast, clofibrate does not inhibit contractions triggered by depolarizing concentrations of K+, in either low or normal Ca medium. Since only receptor-mediated contractions are inhibited, it is suggested that the actions of clofibrate in aorta influence an event common to receptor-linked contractions, possibly by interfering with the utilization of membrane-bound calcium.

Angiotensin II↗

Circular myotomy and esophageal length and safe esophageal anastomosis: an experimental study.

The indication for circular myotomy is often unclear at the time of esophageal atresia repair because the maximal permissible tension at the anastomosis and the precise effect of myotomy on esophageal length and anastomotic tension are not known. This study was undertaken to answer these questions. In piglets, 0 to 6.5-cm segments of thoracic esophagus were excised and approximation force was measured by dynamometers attached to traction sutures in each cut end of the esophagus prior to anastomosis. When approximation force was greater than 75 g. esophageal leaks occurred and increased fibrosis was noted at the anastomosis. Circular myotomy of the upper segment reduced the force necessary to approximate the ends of the esophagus after a 5- to 6-cm resection by about 50%, and double circular myotomy by as much as 75%. When the upper third of the esophagus of piglets and neonatal cadavers was stretched by the application of traction forces of 0 to 75 g. esophageal length increased by about 40%. Thereafter, length increase ws minimal. For any given traction force, each circular myotomy increased esophageal length by about 5 mm. These studies suggest that accurate measurement of approximation force would be useful at the time of esophageal atresia repair. On the basis of these data, circular myotomy(s) is indicated to elongate the esophagus and reduce anastomotic tension when a force greater than 75 g is needed to approximate the esophageal ends.

Animals↗

Ultrastructural changes in the liver in heatstroke.

The ultrastructural changes in the human liver 24 to 96 hours after an attack of heatstroke are described. The alterations are most obvious along the vascular pole of the hepatocytes. These consist of degenerative changes or desquamation of sinusoidal lining cells, ballooning or flattening of microvilli, breaks in hepatocyte outer membranes, and electron-lucent vacuoles along the sinusoidal border. Also noteworthy is the appearance, in a number of cases, of basement membranes or ill-defined electron-dense material which may be of basement membrane character. Sinusoidal elements, such as erythrocytes, are found in hepatocytes, and hepatocellular debris appears in sinusoids. The membranes of hepatocytes and sinusoidal lining cells thus seem to be the prime targets of the hepatic injury in heatstroke. Other changes in the hepatocytes include vesiculation of endoplasmic reticulum, detachment of ribosomes, and alterations of mitochondria. Morphologic evidence of intravascular coagulation of intravascular hemolysis is often encountered. A comparison between the findings described here and those in experimental hyperthermia suggests that many of the hepatic changes seen in heatstroke are due to an excessively high tissue temperature per se but that some of the alterations are probably a consequence of complicating factors such as hypoxia, intravascular hemolysis, or disseminated intravascular coagulation.

Heat Exhaustion↗

Vitamin A-containing lipocytes and formation of type III collagen in liver injury.

Hepatocellular necrosis in carbon tetracholride-induced injury of rats is associated with an accumulation of lipocytes (perisinusoidal cells or Ito cells) containing fat droplets and giving vitamin A fluorescence. In the subsequent formation of connective tissue septa, transitional cells having morphologic characteristics of lipocytes and fibroblasts are abundant and are associated with the appearance of type III collage-. The features suggest that the lipocyte is the precursor of the fibroblasts responsible for parenchymal fibrillogenesis and under these conditions forms type III collagen. The process is a postulated link between hepatocellular necrosis and fibrosis.

Animals↗

Technique for cardiopulmonary bypass in the goat.

The goat is an ideal animal for intracardiac surgical investigation. The animal is docile and easy to care for; it has an ideal heart size, a high cardiac output and a long life expectancy. The animal tolerates cardiopulmonary bypass well and does not require blood transfusion. Anoxic cardiac arrest is tolerated for up to 35 minutes. Initial experience in 36 animals with operations on the right side of the heart resulted in a 72% long-term survival.

Animals↗

The effect of increased pulmonary blood flow on the pulmonary vascular bed in pigs.

Increased pulmonary blood flow was produced in 1-month-old piglets by means of left pneumonectomy, arteriovenous fistulas in the neck, and a combination of both. Physiologic and histologic studies of the pulmonary vascular bed were done 1-9 months after operation. A progressive, moderate increase in pulmonary artery (PA) pressure was observed, especially between 1 and 6 months after surgery. This was flow related, i.e., the group with the highest flow (pneumonectomy plus fistula) was found to have the most prominent increase in pressure. Mean Pa pressure at 6 months was 28.7 +/- 0.07 mm Hg in this group, vs 24.4 +/- 0.48 mm Hg in the group with pneumonectomy alone and 17.2 +/- 0.48 mm Hg in controls (P less than 0.01). The pressure response to hypoxia in pigs with high pulmonary blood flow was not different from that found in control animals. Histologic studies revealed that small arteries and arterioles of pigs with high pulmonary blood flow had a decreased relative wall thickness because of dilation up to 6 months follow-up. This was flow related, the group with the highest flow having the lowest wall thickness to vessel diameter ratio; relative wall thickness (in percentage of the vessel diameter ) at 6 months was 6.1 +/- 0.44% in pigs with with pneumonectomy plus fistula, vs 9.6 +/- 0.40% in the group with pneumonectomy alone and 11.2 +/- 0.61% in controls (P less than 0.01). In the group with the highest flow, thick walled arterioles appeared at 9 months follow-up, scattered among dilated ones; between 6 and 9 months after operation, ranging from 6.1 +/- 0.44% to 11.3 +/- 0.73% (P less than 0.01). In five animals with high flow, the right PA (main branch) showed patchy intimal thickening, small cystic spaces filled with mucopolysaccharides in the media, and muscular hypertrophy.

Animals↗

Morphologic variants of alcoholic hyalin.

Liver biopsies obtained from 24 patients with alcoholic liver disease were studied by light and electron microscopy. Comparisons of the same cells in adjacent sections revealed that alcoholic hyalin is a fibrillar deposit without limiting membranes and is readily distinguished from giant mitochondria. This characteristic fibrillar structure was encountered in hepatocytes, ductular cells and in benign and malignant hepatomas. Three distinct morphologic forms of alcoholic hyalin were observed: a) bundles of filaments in parallel arrays, b) clusters of randomly oriented fibrils and c) a granular or amorphous substance containing only scattered remains of fibrils. Closely associated with alcoholic hyalin and often found along its entire circumference, were bundles of fine filaments in parallel arrangement of much smaller size. These occasionally displayed variations in orientation and merged with the filaments in the alcoholic hyalin body. Similar fine filaments were observed, in considerable excess, in cells which did not contain alcoholic hyalin. According to our findings, the fine filaments and the significantly larger filaments in alcoholic hyalin could be parts of a contractile system elaborated by host cells during the course of hepatic injury.

Alcoholism↗