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Biomedical subjects

G T Smith

Publications and source records attributed to G T Smith.

At least 109 records · Page 6Linked to original sources

Failure of nifedipine therapy to reduce myocardial infarct size in the baboon.

The value of nifedipine in reducing the ultimate size of an infarct associated with a period of coronary occlusion followed by reperfusion was assessed. Eight baboons were administered a bolus dose of nifedipine, 5 micrograms/kg intravenously, and then a maintenance dose of 30 micrograms/kg per hour was begun 1 hour before occlusion. This regimen resulted in an 8.5 +/- 1.2 percent (mean +/- standard error) decrease in mean arterial pressure. The left anterior descending coronary artery was occluded for 2 hours and then perfusion restored. At 2 hours after reperfusion the nifedipine infusion was discontinued. Eight control baboons underwent an identical protocol without nifedipine therapy. At 24 hours after occlusion, microvascular dyes were injected into the left anterior descending coronary artery and adjacent arteries to delineate the perfusion bed of the previously occluded artery. The volume of infarction was determined with planimetry and compared with the volume of the perfusion bed of the occluded artery. The area of infarction was always contained within the perfusion bed of the occluded artery. The mean percent of the perfusion bed with infarction was 50.1 +/- 5.8 in the control group and 41.7 +/- 9.5 in the treated group (difference not significant; p greater than 0.05). In both control and treated groups of baboons hemorrhage occurred only within the region of infarction. In both groups electron microscopy revealed large electron-dense granules within the mitochondria. In conclusion nifedipine therapy during a 2 hour period of coronary occlusion followed by reperfusion did not result in any significant reduction in ultimate infarct size in the baboon.

Animals↗

Quantitative assessment in infarct size reduction by coronary venous retroperfusion in baboons.

Initial favorable reports in which coronary venous retroperfusion was begun after acute coronary artery occlusion have demonstrated a reversal of ischemic injury and improved left ventricular function. However, little information has been generated to document the extent to which retroperfusion may decrease ultimate histologically determined infarct size. The objective of the present study was to evaluate the effectiveness of retroperfusion in reducing infarct size by using an accurate quantitative method in which infarct size was related to the size of the anatomic perfusion bed of the occluded artery (region at risk for infarction). In an experimental group of 5 baboons, the left anterior descending coronary artery was occluded and coronary venous retroperfusion started 1 hour after occlusion. After a 4-hour period of occlusion, retroperfusion was discontinued and anterograde perfusion was simultaneously restored. A control group of 5 baboons underwent an identical procedure without retroperfusion. Twenty-four hours after occlusion, hearts were excised and the previously occluded left anterior descending coronary artery as well as the adjacent arteries were infected with microvascular dye to delineate the perfusion bed of the occluded artery. Planimetry of serial corss-sections of the left ventricle enabled the size of the perfusion bed of the occluded artery and size of the infarct to be determined. The mean percentage of the perfusion bed infarcted in the control group was 94.1 +/- 0.9 (mean +/- standard error) and in the retroperfused group was 57.4 +/- 3.5 (p less than 0.001). Hence, the results demonstrated that when retroperfusion was initiated after 1 hour of coronary occlusion, the mean percentage of the perfusion bed salvaged was increased by 36.7%.

Animals↗

Natural killer cell activity and response to phytohaemagglutinin compared with the histological diagnosis of patients with transitional cell carcinoma of the bladder.

In vitro tests of immune reactivity in patients with transitional cell carcinoma (TCC) of the urinary bladder were compared with the clinical and histological diagnosis. Response of peripheral blood lymphocytes to the mitogen phytohaemagglutinin (PHA) tended to be reduced in patients with more advanced disease, although the difference between patients with advanced disease and those with early disease or controls was not statistically significant (P greater than 0.05). Assessment of natural killer (NK) cell activity in the same patients showed no change in levels of reactivity at any stage of the disease. There was no difference between the NK cell activity of patients with TCC of the bladder and normal controls.

Aged↗

Quantitative effect of early coronary artery reperfusion in baboons. Extent of salvage of the perfusion bed of an occluded artery.

We examined the extent to which ischemic myocardium was salvaged by reperfusion using a method that allowed expression of the volume of infarction as a percentage of the volume of the perfusion bed of the occluded artery (region at risk of infarction). In eight baboons, the left anterior descending coronary artery (LAD) was occluded for 2 hours, after which perfusion was restored. A control group of eight baboons underwent an identical protocol, but perfusion was not restored. Twenty-four hours after occlusion, microvascular dyes were injected into the LAD and adjacent arteries to delineate the perfusion bed of the occluded artery. The volume of infarction and volume of the perfusion bed were determined planimetrically. The mean percentage of the perfusion bed infarcted in the control baboons was 94.2 +/- 3.5% and 50.1 +/- 5.8% in the reperfused baboons. Hence, the mean percentage of the perfusion bed infarcted was reduced by 44.1% in the reperfused group compared with the control group (p less than 0.001). In reperfused baboons, hemorrhage occurred in the region of infarction but did not result in infarct extension. We conclude that reperfusion after 2 hours of coronary occlusion results in substantial salvage of ischemic myocardium in the baboon.

Animals↗

Diabetes mellitus with ketoacidosis presenting as Fournier's gangrene.

Two patients with Fournier's gangrene are described. In each case this was the presenting clinical feature of diabetes mellitus with ketoacidosis. Histological examination demonstrated that the probable cause was intravascular fibrin deposition. The association between diabetes mellitus and Fournier's gangrene is discussed.

Aged↗

Reduction in infarct size by synchronized selective coronary venous retroperfusion of arterialized blood.

The effectiveness of selective synchronized pulsatile coronary venous retroperfusion for the temporary metabolic support of a region of acutely ischemic myocardium has previously been demonstrated. This study was designed to determine the degree of reduction in ultimate infarct size that may be achieved when coronary venous retroperfusion initiated early after coronary occlusion is combined with later anterograde reperfusion. In 10 baboons, the proximal left anterior descending coronary artery was occluded for 4 hours at which time anterograde reperfusion was restored. In five baboons (Group A), coronary venous retroperfusion was initiated 15 minutes after occlusion. Five baboons (Group B) underwent an identical procedure without coronary venous retroperfusion. Epicardial electrograms were recorded from 24 sites overlying the ischemic region. At 24 hours, hearts were excised and serial transverse sections of the left ventricle were stained with nitroblue tetrazolium for stereometric determination of infarct size. In Group A 12 +/- 5.4 percent (mean +/- standard error of the mean) of epicardial sites with S-T segment elevation at 15 minutes after occlusion showed subsequent Q waves, compared with 96 +/- 2.3 percent in Group B (p less than 0.01). In Group A 4.8 +/- 1.7 percent of the left ventricular mass was infarcted, compared with 30.6 +/- 4.2 percent in Group B (p less than 0.01). The results demonstrated the effectiveness of coronary venous retroperfusion in preserving ischemic myocardium such that anterograde reperfusion resulted in a mean reduction of 84 percent in ultimate infarct size.

Animals↗

Hemorrhagic infarction and coronary reperfusion.

Coronary ligation experiments were performed on 23 primates. Some of the experiments were followed by reperfusion after periods of occlusion of from 1 to 6 hours. Hemorrhage into the infarct was noted in all animals and was greatest following reperfusion after 4 hours of occlusion or longer. Hemorrhage increases the measured infarct size to the point that it is actually larger than that seen with ligation alone. However, this increase is accounted for by the larger amount of intramyocardial hemorrhage. Hemorrhage is greatest in the center of the infarct and decreases at the margins. It appears that hemorrhage occurs into necrotic muscle and does not occur significantly at the margins of the infarct where damage to otherwise viable myocardium might result.

Animals↗

Effect of left ventricular--to--aortic bypass on infarct size and infarct microcirculation in baboons.

A major diagonal branch of the left anterior descending coronary artery (LAD) was acutely occluded in 17 baboons. Complete left ventricular (LV) decompression was achieved with a left heart bypass (LHB) system in six baboons while 11 baboons served as untreated controls. In the treated group, LHB was initiated after 30 minutes of coronary occlusion. For a period of 6 hours after occlusion, aortic pressure, LV pressure, left atrial pressure, and cardiac output were monitored. During the same monitoring period, electrograms were recorded from a high resolution matrix of fixed epicardial electrodes. Regional myocardial blood flow was determined prior to and at intervals following the initiation of LHB with radioactive microspheres. Infarct size was assessed histologically from serial cross sections of the left ventricle. The degree of salvage achieved by LHB was assessed by comparing the epicardial area of infarction 6 hours after occlusion (AI) to the area of epicardial St-segment elevation (STE) 30 minutes after occlusion (maxAST). In the LHB-treated group, 40.0% +/- 8.1% (SEM) of maxAST showed subsequent infarction; in the control group, 79.8% +/- 2.7% of maxAST showed eventual infarction (p less than 0.01). STE overlying the region of ischemia in the LHB-treated group did not undergo the spontaneous decline observed in the control group, which is normally associated with the progression of necrosis. Regional myocardial blood flow did not change significantly in the ischemic region during the period of occlusion following LHB. LHB. The results suggest that LHB is capable of substantial salvage of acutely ischemic myocardium by reducing myocardial work and thus reducing myocardial oxygen requirements.

Animals↗

Quantitative effect of a single large dose of methylprednisolone on infarct size in baboons.

Despite numerous studies directed at determining the ability of glucocorticoids to minimise myocardial ischaemic damage following acute coronary occlusion, there remains no clear consensus concerning their usefulness. Within an ischaemic region, glucocorticoids produce membrane stabilising effects which decrease the autolytic effects of marked cellular swelling and lysosomal membrane rupture. Their use has also been associated with a decreased cellular lysis due to infiltrating inflammatory cells and with an increase in collateral blood flow. The use of glucocorticoids has remained clinically attractive due to experimental observations regarding these local actions; however, the potential of these actions to enhance long-term viability of ischaemic myocardium has remained uncertain. A major problem in the comparison of the extent of infarction between treated and untreated animals has been the variability in infarct size that results from coronary artery ligation at any given anatomical site. In the experimental baboon model which we have employed, we have previously shown that the ultimate epicardial area of infarction, as well as the volume of infarction as assessed histologically at 7 days post occlusion, shows a good linear relationship to the area of ischaemic injury at 1-hour post occlusion, as assessed by high resolution epicardial ST segment mapping. In this way animals may serve as their own controls and as long as an intervention is initiated at 1 h or later post occlusion, then the epicardial area or transmural volume of histologically assessed infarction at 7 days can be compared with the predicted epicardial area or transmural volume of infarction and hence determine the effect of that intervention in altering infarct size. This experimental model does not rely on a comparison of the absolute magnitude of infarcts between treated and untreated animals and, therefore, avoids the error introduced by the inherent variability in infarct size between animals after coronary occlusion.

Animals↗

Dual primary adenocarcinoma of the duodenum and jejunum in a patient with previous colonic cancers.

Primary adenocarcinoma of the small intestine is an uncommon tumour, the incidence being 40-60 times less frequent than carcinoma of the colon. Multiple primary neoplasia of the small bowel, although not infrequently seen with benign growths, is an extremely rare event with malignant lesions. A patient is described who had an adenocarcinoma of the duodenum and jejunum, with a previous history of colonic carcinomas. The case is discussed together with a brief review of the literature.

Adenocarcinoma↗

Induction of rat sarcomas in rats treated with antithymocyte sera after transplantation of human cancer cells.

Human cancer cells that had had high (greater than 160) tissue culture passages, when transplanted into antithymocyte-treated F344 newborn rats, caused induction of rat sarcomas in the rats within 2 or 3 subcultures, whereas human cancer cells with low (5-33) passages in vitro did not cause overt induction of rat sarcomas until after 5-10 subtransplantations. Because oncornavirus activity was not detected in either rat or human tumors, it is suggested that transforming sequences located on the human tumor cells may have been transferred to supporting rat reticulum cells in close contact with the human cancer cells.

Animals↗

Epicardial mapping and electrocardiographic models of myocardial ischemic injury.

The amplitude and distribution of epicardial ST-segment elevation (ST) were examined for an 8-hour period after coronary occlusion in eight baboons and five pigs. ST was determined from unipolar epicardial electrograms obtained from a high-resolution matrix of fixed electrodes overlying a transmural region of ischemia. A relatively uniform degree of ST was observed overlying the ischemic region for 20 minutes after coronary occlusion. A gradient in ST from the periphery to the center of the ischemic region was documented after 20 minutes of ischemia. In 10 other pigs, change in the degree of ST was examined contingent on either an increase (five pigs) or decrease (five pigs) in the size of the ischemic region after 1 hour of preexisting ischemia. An abrupt increase in the number of electrodes that showed ST (NST) from 7.8 +/- 1.24 (SEM) to 14.8 +/- 1.35 (90%) was associated with an increase in mean ST of 58% from 4.28 +/- 0.61 mV to 6.78 +/- 0.84 (p less than 0.05). An abrupt decrease in NST from 25.2 +/- 2.63 to 14.6 +/- 2.22 (42%) was associated with a decrease in mean ST of 24%, from 8.2 +/- 0.36 mV to 6.3 +/- 0.30 mV (p less than 0.01). The results during early ischemia (less than 20 minutes of ischemia) are accurately represented by a model of ischemia in which injury current arises only at the ischemic boundary. The results during later ischemia (after 20 minutes of ischemia) may be represented by a model in which ST is considered dependent on injury currents generated throughout the ischemic region.

Animals↗

Outcomes of teacher preparation in allied health sciences.

Formal preparation of allied health instructors for responsibilities of teaching and educational leadership has been encouraged through substantial federal grants, institutional funds and university programming. A review of the literature reveals very little regarding formal measurements of outcomes in terms of career progress of the graduates their professional activities and their level of satisfaction with the educational content and preparation as a teacher. This study focuses on the achievements and opinions of 106 graduates of a master's degree teacher preparation program. Graduates were found to be employed in positions commensurate with their preparation, and rewarded by their employers with career advancement, salary increases and promotions. The graduates believed that they had gained the skills needed. They also identified the strengths and weaknesses of the program. Implications of the findings are discussed.

Career Mobility↗

Specific potentiation of L1210 vaccine by pyran copolymer.

Pyran copolymer (NSC 46015) was found to potentiate strongly the immune response of C57BL/6J X DBA/2 F1 mice to 10(4) live L1210 tumor cells following suboptimal vaccination with 10(7) radiation-inactivated L1210 cells. Optimal immunity to challenge was produced by concomitant i.p administration of pyran and L1210 vaccine, and activity was dependent upon both pyran and vaccine dosages. In addition, this immunopotentiation seemed to be related to the intrinsic viscosity of different pyran preparations tested, although all the pyran compounds had significant activity. Furthermore, the increased immunity of subsequent live tumor challenge appeared to be specific for the vaccinating cell type.

Animals↗

Oxygen consumption changes with stored blood infusions.

Stored blood contains microaggregates, often implicated in the pathogenesis of post-traumatic pulmonary insufficiency. This study was an attempt to further elucidate the effect of autologous stored, filtered and non-filtered blood infusions and homologous stored and fresh blood infusions on pulmonary function and hemodynamics. Inconsistent changes in pulmonary hemodynamics and blood oxygenation were noted. The one significant finding was an increase in oxygen consumption, which occurred with unfiltered autologous or homologous blood but not with fresh or filtered blood. Since an increased oxygen consumption results in an oxygen demand which is difficult to meet in the face of multiple other injuries, it is conceivable that this observation implicates massive stored blood transfusion as a major contributing factor in the development of so-called irreversible shock.

Animals↗