Résumé of 400 cases of acute upper digestive tract bleeding treated by rhubarb alone.
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Biomedical subjects
Publications and source records attributed to C T Liu.
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Experiments were conducted to determine the dose response, survival time, blood biochemical changes, and cardiohepatic responses to a single IV injection of crude Shigella toxin in rhesus macaques (Macaca mulatta). Circulatory shock, hepatic falure, respiratory depression, dyspnea, convulsions, and coma were observed before death. The survival time was inversely related to the administered toxic dose, which ranged from 20 to 200 microgram/kg of body weight. However, the severity of lesions in the heart and gastrointestinal tract was directly correlated with the amount of the injected dose. Macaques exposed to aerosols of crude Shigella toxin did not show any signs of toxicosis within 7 days after exposure and were considered permanent survivors. Seemingly, an IV crude preparation of Shigella toxin is lethal to rhesus macaques, but an aerosol crude preparation of Shigella toxin is not.
A case of advanced idiopathic arterial calcification occurred in a macerated male fetus, 29 weeks' gestational age, delivered of a 22-year-old primigravida. The aortic valve, aorta, coronary arteries, ductus arteriosus, and pulmonary, mesenteric, periadrenal, and renal arteries were calcified and were detected on postmortem roentgenogram. Myocardial calcification and endocardial fibroelastosis were also present. The mother's calcium, phosphorus, and alkaline phosphatase levels were normal. Vitamin D intake was not excessive. A maternal febrile illness at 18 to 19 weeks' gestation was the only untoward event during pregnancy.
Intramuscular injection of staphylococcal enterotoxin B (SEB) at a dosage level of 50 microgram/kg of body weight caused death in Dutch rabbits. Lethality was not modified markedly by morphine pretreatment or by hyperthermia, thyrotoxicosis, propylthiouracil feeding, thyroparathyroidectomy, water deprivation, or fasting. The administration of acetylsalicylic acid to the SEB-inoculated rabbit also failed to protect the rabbits from the effect of SEB. Seemingly, the SEB molecular destruction was not markedly modified by alteration of cellular metabolism, and lethal effects of SEB remained unchanged in the morphine- or acetylsalicylic acid-treated rabbits. When SEB was given to six rabbits 3 days after total-body X-irradiation, fever persisted and three rabbits survived. An identical dose of SEB to nonirradiated rabbits produced fever initially, followed by hypothermia and death of all six rabbits.
A crude preparation of leukocytic endogenous mediator administered IV over a 10-minute period into a rhesus macaque at a dosage of 10 ml/kg of body weight resulted in hypotension, tachycardia, vasodilation, hypoalbuminemia, and hypoproteinemia. Decreases in cardiac and hepatic functions and biphasic changes in peripheral polymorphonuclear leukocytes also were seen. All measured changes, except hepatic functions and plasma albumin values, returned to base-line values within 24 hours. Data indicate that presently utilized crude leucocytic endogenous mediator preparations contain a heretofore undescribed, and as yet unidentified, component. Induced early cardiovascular changes may be related in part to certain compounds likely to be in the crude preparation.
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Chair-restrained rhesus monkeys (Macaca mulatta) were inoculated subcutaneously with 10(2)--10(3) plaque-forming units of virulent Rickettsia rickettsii. The latent period for fever and rickettsemia was three to four days; death occurred six to eight days after infection. Total circulatory electrolyte levels and fluid volumes, including plasma, red blood cell, true circulatory blood, and extracellular fluid, increased. The expansion of the extracellular and plasma volumes resembled findings reported during severe Rocky Mountain spotted fever in humans, guinea pigs, and rabbits. Total water content of the liver also increased. Intracellular concentrations of K+, as well as total Na+ and K+, decreased in the diaphragm. Both the lung and medulla oblongata showed increased levels of intracellular Na+ and water with simultaneously decreased levels of extracellular Na+ and water. Such an intracellular overhydration of the medulla oblongata could contribute to death as a result of depression of the cardiovascular and respiratory centers. On the basis of the findings in monkeys, the intravenous infusion of fluids and electrolytes during clinical therapy of severe rickettsial infections should be considered extremely dangerous.
Techniques for the determination of water and electrolytes in individual tissues of normal rhesus macaques (Macaca mulatta) are described. Base-line values are presented for intracellular and extracellular distributions of water and electrolytes in 14 tissues, including skin, skeletal muscle (gastrocnemius), cardiac muscle (left ventricle), lung, diaphragm, liver, renal cortex, outer medulla and inner medulla, cerebral cortex, cerebellum, thalamus-hypothalamus complex, medulla oblongata, and spinal cord.
Selected cardiovascular and renal functions were measured for 5 hours in conscious, chair-restrained, female rhesus macaques (Macaca mulatta) after IV (0.05 and 1.0 mg/kg) or oral (1.0 mg/kg) administration of staphylococcal enterotoxin B (SEB). Cardiovascular functions, renal hemodynamics, and renal metabolism were also studied between 6 and 11 hours after IV SEB inoculation. Oral SEB produced few changes in cardiorenal functions. In contrast, IV SEB produced hypotension, tachycardia, increased total peripheral and renal vascular resistance, and decreased cardiac and renal functions. The early significant (P less than 0.05) renal depression was not associated with hypotension (mean arterial blood pressure greater than 100 mm of Hg). However, all measured renal functions except extraction ratio of PAH were positively correlated with decreased blood pressure (r = 0.52 - 0.71) in the later phase of SEB toxemia. It is concluded that the kidney is one of the organs affected by IV SEB. Renal impairment may partially contribute to death during SEB enterotoxemia in macaques.
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Pretreatment of rhesus macaques with nonlethal total-body x-irradiation (400 R) prolonged survival time from an average of 15 hours to 101 hours after intravenous (IV) inoculation of 50 microgram of staphylococcal enterotoxin B (SEB)/kg of body weight. Radiation exposure per se did not produce detectable cardiorenal changes; however, the longer survival after SEB challenge exposure in x-irradiated rhesus macaques was associated with improved cardiorenal functions if compared with that of nonirradiated macaques given the same dose of SEB. Total-body radiation exposure 4 days prior to IV SEB inoculation prevented typical SEB-induced decreases (where measured at 5 hours) in cardiac output, stroke volume, TcH2O, CPAH, Cosm, and urine flow, as well as increases in total peripheral and renal resistance. A theory concerning the significance of radiation-induced leukopenia on modification of SEB-induced cardiorenal functions is postulated.
Antisera which react with the major metabolites of cocaine have been prepared in rabbits and a hemagglutination-inhibition (HI) test which detects these metabolites in urine or serum in concentrations of 1 ng/ml is described. A comparison of this test with alternate detection procedures shows excellent agreement at comparable sensitivity levels. HI tests on simian and human biological specimens suggest that the use of cocaine remains detectable for at least 3 days after administration of a minimal pharmacologically active dose. Combination of physical separation of drug metabolites with immunoassay procedures indicates that benzoylecgonine and ecgonine are the immunoreactive cocaine metabolites found in human urine. While it was possible to apply the HI test at maximal sensitivity to human sera and to murine or simian urine specimens, interference was encountered with some human urine specimens. Preliminary data suggest that by reducing the sensitivity of the test to a threshold of 200 ng/ml this interference can be overcome.
Alterations occur in human muscle electrolyte and water composition in response to infection. There appear to be at least two basic mechanisms; the first is an exchange of sodium for potassium without alteration in water content of muscle. The second is an increase in cellular Na and water without a loss of K on a dry weight basis. In a series of studies in monkeys, Salmonella typhimurium sepsis was induced as an experimental model. Both patterns of muscle response to infection were detected. Electron probe microanalysis revealed that the loss of K concentration was due to an accumulation of intracellular saline which dilute the K content. The mechanism of this is unclear; however, a concomitant increase in undertermined osmoles in the serum suggests that there may be an increase in organic osmoles within the cell which leads to the dilution of intracellular K concentration.
Selected cardiorenal functions for conscious and chaired rhesus macaques were compared directly and indirectly with corrections for body weights and surface areas to well-established base-line values for human subjects. Certain functional differences between species and conditions of measurement do not allow all experimental results from the rhesus macaque to be extrapolated to man. However, this comparative study provides evidence that can be useful in attempting to evaluate cardiorenal data from macaques in relationship to human studies.
Techniques for measurements of selected pulmonary functions for a period of 6 hours in conscious and lightly anesthetized rhesus macaques are described. Among all variables measured, only higher PaCO2 (367 +/- 32 mm of Hg) occurred in macaques breathing O2 as compared with those breathing room air. Tidal volume, respiratory rate, minute volume, O2 consumption, and specific ventilation in conscious and anesthetized monkeys were not significantly different. Further, respiratory and metabolic values from lightly anesthetized macaques in the present study agree well with the reports of others. However, differences were the higher values for O2 consumption, tidal volume, respiratory rate, and minute volume obtained with the presently described techniques as compared with certain reported data.
Certain cardiovascular and hepatic functions were measured for a period of 6 to 14 hours in conscious, chaired, male rhesus macaques given (intravenously (IV) or orally) staphylococcal enterotoxin B (SEB). In macaques orally given SEB (1 mg/kg), there was little change in the cardiovascular variables. The half-life of injected indocyanine green was apparently prolonged in macaques given SEB as compared with that in the controls. However, in macaques given SEB (0.05 or 1.0 mg/kg) by IV injection, there were tachycardia, increase in arterial resistance, and decreases in blood pressure, cardiac output, stroke volume, cardiac work, mean cardiac power, and central blood volume. In addition, mean transit time from caudal vena cava to ascending aorta was prolonged and a simultaneous reduction of hepatic removal of indocyanine green occurred.
Body surface areas (BSA) of 31 apparently normal rhesus monkeys of both sexes weighing 3.2-5.3 kg were determined by the direct skinning technique. The range of measured BSA was 1,940-3,020 cm2 (mean = 2,430 cm2). The BSA values of male and female monkeys were not significantly different. The K value, calculated as the ratio of BSA (cm2)/body wt2/3 (kg), was 969 +/- 15 (SE). Based on the principle of least squares for goodness of fit between the measured and calculated BSA, the best equation was determined to be (see article). A nomogram was constructed for rapid determination of the BSA of rhesus monkeys with known body weight and lengths (head to anus). Monkey BSA could also be computed by multiplying the DuBois human BSA equation by a factor of 1.147 for the head-to-anus measure of length or by 0.891 for the head-to-heel measurement.
Techniques for measuring changes in body fluid compartments after SEB injection i.v. in conscious rhesus monkeys are described and compared with base line values measured by identical techniques in normal monkeys. Although few changes were observed in body fluid volumes 3 h after i.v. staphylococcal enterotoxin B (SEB; 1 mg/kg), the F cell ratio and all fluid compartments except for RBC volume were decreased significantly by 5 h after i.v. SEB administration. Rapid intracellular dehydration and decreases in plasma and blood volumes appear to play a role in the development of circulatory shock during enterotoxemia in monkeys.