Mothers of incest victims.
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Biomedical subjects
Publications and source records attributed to C W Christensen.
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Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20.
Two-dimensional echocardiography using echo-contrast enhancing agents is a promising technique for evaluating myocardial perfusion. However, the potential deleterious effects of injection of echo-enhancing agents into the coronary circulation have not been well evaluated. We utilized two experimental canine models in which the left anterior descending coronary artery was cannulated and perfused continuously by the left common carotid at normal and reduced coronary flows. Analysis of myocardial function included regional left ventricular systolic function by ultrasonic crystals, subendocardial ST segment shifts, left ventricular dP/dr analysis and measurements of coronary blood flow. One ml of each echo-contrast agent was injected into the left anterior descending coronary artery during normal coronary flow. Echo-enhancing agents included: sonicated 70% sorbitol, 50% dextrose, and 6% dextran, hand-agitated Renografin-saline, and unagitated 0.15% hydrogen peroxide, 20% fat emulsion and oxygenated Oxypherol, a perfluorocarbon compound. Two-dimensional echocardiography determined that all echo-enhancing agents except for 20% fat emulsion and Oxypherol produced good myocardial enhancement. All echo-enhancing agents which produced a good contrast effect did so at the expense of significant reversible contractile abnormalities. Each produced more than a 50% reduction in percent segment shortening. Sorbitol and hydrogen peroxide produced the most severe contractile disturbances. In the normal flow model, sorbitol produced systolic bulging and hydrogen peroxide an 83% reduction in percent segment shortening. Hydrogen peroxide induced systolic bulging in the reduced coronary flow model. Other abnormalities induced by echo-enhancing agents included ST segment shifts and malignant ventricular arrhythmias. Six percent dextran produced a good contrast effect with the least harmful myocardial consequences.
The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS)
This investigation was performed to determine whether the abrupt withdrawal of chronically administered nitroglycerin (NTG) alters coronary vascular resistance and myocardial perfusion in an experimental rabbit model. New Zealand white rabbits received 2 inches of topical NTG (2%) applied 3 times daily over a 6 week period. Forty hours after abrupt withdrawal of NTG left ventricular blood flow was assessed by the radioactive microsphere technique. Coronary resistance was significantly increased in NTG-withdrawal rabbits at the baseline (21.5 +/- 3.1) compared to controls (13.5 +/- 1.2) and remained elevated after ergonovine administration at both the early (NTG-withdrawal: 20.9 +/- 3.5 vs controls 12.6 +/- 1.5) and late (NTG-withdrawal: 17.1 +/- 3.1 vs controls: 11.6 +/- 0.9) sampling periods. Neither ergonovine nor indomethacin significantly altered blood flow compared to earlier values. However, the NTG-withdrawal rabbits exhibited significantly lower blood flow to the left ventricle compared to controls after ergonovine administration at both early (NTG-withdrawal: 4.80 +/- 0.72 ml/min/gram vs controls: 6.98 +/- 0.79 ml/min/gram) and late (NTG-withdrawal: 5.30 +/- 0.80 ml/min/gram vs controls: 7/52 +/- 0.66 ml/min/gram) sampling periods and also following indomethacin administration (NTG-withdrawal: 4.24 +/- 0.46 ml/min/gram vs controls: 7.52 +/- 1.26 ml/min/gram). Electrocardiographic evidence of myocardial ischemia was noted in the NTG-withdrawal rabbits following intracardiac injection of microspheres. These studies show that increased sensitivity of NTG-withdrawal rabbits to ergonovine or microsphere injection is associated with increased coronary vascular resistance. However, severe myocardial ischemia was not observed.
Like breast carcinomas, endometrial carcinomas are derived from sex steroid target tissue. Progress and research directed into the clinicopathologic relationship of steroid receptors and endometrial carcinomas have been hampered by many factors, including: limited numbers of patients with advanced-stage disease compared to the number with breast carcinoma; contamination of specimens with surrounding benign endometrial components which may contribute to total steroid binding; and amount of tissue required for standard biochemical assays. Nevertheless, several clinicopathological associations have been made for steroid receptor content of endometrial carcinomas. Receptor content appears to correlate with histological differentiation in that well-differentiated lesions have higher mean levels of receptor and more receptor 'positive' lesions than do poorly differentiated lesions. Furthermore, receptor levels and status appear to correlate with prognosis of primary endometrial carcinomas and response to hormonal therapy of advanced endometrial carcinoma. Newer techniques utilizing monoclonal antibodies to directly localize receptor in tissue specimens may lead to a greater understanding of the dynamics of receptor physiology in endometrial carcinomas, and may make possible more accurate predictions of clinical behavior by allowing the direct analysis of the receptor content of the malignant component within a tissue specimen.
Intracoronary administration of the H2 receptor agonists impromidine and dimaprit at doses that did not alter systemic hemodynamics increased coronary blood flow but had no regional positive inotropic effects. Dose-related increases in myocardial blood flow were observed with both drugs. These effects were attenuated by prior administration of cimetidine. The results of this study demonstrate that H2 coronary receptor stimulation results in vasodilation of both subepicardial and subendocardial regions.
We examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [3H]serotonin and the extravascular volume accessible to [14C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.
The objectives of this study were to develop a surgical procedure that would allow for bilateral isolated lung perfusion in vivo as a means of delivering organ-specific chemotherapy and to evaluate the influence of the procedure on certain pulmonary physiologic parameters. The sterile surgical procedure that was carried out in dogs involved the setting up of two separate perfusion circuits. Once standard systemic cardiopulmonary bypass was established, a second circuit was devised to perfuse the lungs by placing an inflow cannula into the main pulmonary artery and collecting venous effluent in the left atrium. Cross-contamination between perfusion circuits was determined in acute studies with labeled plasma protein or red blood cells and was found to be in an acceptable range if the aorta was cross-clamped and the heart arrested. Only about 0.4 ml/min of pulmonary perfusate leaked into the systemic circulation, indicating that systemic toxicity should not be a major concern when chemotherapy agents are added to the pulmonary perfusate. Chronic studies demonstrated that hemodynamic parameters, lung water, pulmonary endothelial serotonin extraction, and histologic findings all showed minimal changes after 50 minutes of isolated lung perfusion. Five days after perfusion, lung dynamic compliance and peak serotonin extraction showed significant decreases. However, all of the measured parameters had returned toward baseline levels by the end of the 8-week postoperative study period. The procedure offers significant advantages over the previously described single lung perfusion and may provide a method of delivering immediate high-concentration adjuvant chemotherapy to coincide with resection of primary or metastatic lung tumors.
The i.p. injection of Cd in mice will produce a dose related hypothermic response. The Cd appears to make the animals poikilothermic and their body temperature will approach the ambient temperature at which they are housed. The cause for this hypothermic action of Cd is not known, but we have demonstrated in our experiments that the effect may be partially related to a direct effect within the brain. In addition, the repeated injection of a low Cd dose (0.62 mg/kg) i.p. once daily for 3 days results in a profound tolerance to the Cd. A high dose (1.25 mg/kg i.p. once daily X 3 days) of Cd did not result in a similar tolerance phenomenon and a single injection of the high Cd dose 120 hr prior to the repeated low Cd dose regimen resulted in an obtunded tolerance response to the low dose. We propose that the higher Cd dose may have damaged the blood-brain barrier and this could account for the results we have observed.
The effect of histamine (H) and specific H1 and H2 agonists and antagonists on regional myocardial blood flow was studied in anesthetized dogs by use of tracer microspheres. Intracoronary infusion of histamine (15 and 34 micrograms/min) produced a dose-related increase in transmural myocardial blood flow (from 0.82 to 1.36 and 2.25 ml X min-1 X g-1) without alteration of heart rate or blood pressure. Infusion of the H1 agonist 2-(2-thiazolyl)ethylamine (135 and 442 micrograms/min) produced an increase in transmural perfusion (from 0.69 to 1.22 and 1.65 ml X min-1 X g-1) and a significant (P less than 0.05) increase in the ratio of flow between subendocardium and subepicardium (endo/epi from 0.97 to 1.31 and 1.54). Infusion of the H2 agonist dimaprit (195 and 390 micrograms/min) produced an increase in transmural myocardial blood flow (from 0.97 to 1.49 and 2.00 ml X min-1 X g-1) without a change in endo/epi. The H1-mediated increase in regional myocardial perfusion and endo/epi was blocked by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. These results suggest that stimulation of H1 coronary receptors preferentially distributes flow to the subendocardium, whereas H2 receptors mediate vasodilation in subepicardium as well as subendocardium.
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It has been suggested that the peptides alpha-metanocyte stimulating hormone (alpha-MSH) and MSH-release inhibitory factor (MIF-1) may alter adenosine-3', 5'-cyclic monophosphate (cAMP) metabolism [13,26]. Normal and hypophysectomized (hypoxed) rats were administered saline (controls IP daily X 3), alpha-MSH (80 mug/kg IP daily X 3) or MIF-1 (1 or 10 mg/kg IP daily X 3) and sacrificed 30 min after the third injection in a focused microwave oven (1.5 KW; 2-3 sec). Various brain areas were then assayed for cAMP levels after each treatment. The occipital cortex area was the only area to show consistent changes in both normal and hypoxed rats after alpha-MSH treatment. These findings were replicated for the occipital cortex in a second group of normal and hypoxed rats which were similarly treated. The results suggest a correlation between the rise in cAMP found and reported changes in visual acuity and attention in rats and human after treatment with alpha-MSH [8,14, 23].