Studies on platelet aggregation in vivo. VII: Effect of pentoxyfylline on circulating tumor cells.
Pentoxifylline, a platelet aggregation inhibitor, increased circulation time of intravenously injected, labeled tumor cells in male mice.
Animals↗
Biomedical subjects
C M Ambrus
Publications and source records attributed to C M Ambrus.
Preparation of immobilized L-phenylalanine ammonia-lyase in tubular form for depletion of L-phenylalanine.
The enzyme L-phenylalanine ammonia-lyase (EC 4.3.1.5), which catalyzes the conversion of L-phenylalanine into trans-cinnamic acid, was adsorbed in the walls of asymmetric hollow fibers and covalently bound to the innerwall of small bore nylon tubing. Multi-tubular enzyme reactor cartridges were constructed both from hollow fibers and nylon tubes and the capacity of the reactors to degrade phenylalanine at physiological concentrations was evaluated in perfusion studies at different flow rates ranging from 30 to 80 ml/min. Hollow fiber enzyme reactors showed significantly higher activity than nylon tube reactors of commensurable dimensions and this finding is attributed to the difficulties in immobilizing L-phenylalanine ammonia-lyase via covalent linkages. The results suggest that extracorporeal use of such multi-tubular enzyme reactors offer a promising approach to deplete serum phenylalanine levels.
Ammonia-Lyases↗
Progestational agents and blood coagulation. VIII. Effect of low-dose, alternate-day, estrogen-progestin combinations on blood coagulation factors in man, with a special note on the effect of freezing of blood samples.
Changes in the blood coagulation system were studied in three groups of 20 patients each. The first group received 0.5 mg. of norethindrone daily, plus 0.06 mg. of ethinyl estradiol on alternate days from cycle Day 5 through 25. The second group, all of whom had been fitted with an intrauterine contraceptive device (IUD), received no hormonal treatment and served as a control group. The third group received 0.5 mg. of norethindrone daily, combined with 0.045 mg. of ethinyl estradiol given on alternate days from cycle Day 5 through 25. Blood samples were drawn prior to the initiation of the study and after three months of treatment. Tests of the following parameters of the blood coagulation system were performed: direct platelet count; platelet adhesiveness; prothrombin time; thrombin time; fibrinogen; factor II assay; activity of factors V, VII, VIII, IX, and X; antithrombin III; and fibrin/fibrinogen degradation products. For a number of these factors, both fresh and frozen blood samples were examined. It was concluded that the two treatment regimens, with the use of alternate-day estrogen administration over a three-month period, had no clinically significant effect on the blood coagulation system.
Adolescent↗
Prevention of hyaline membrane disease with plasminogen. A cooperative study.
In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.
Clinical Trials as Topic↗
Study of platelet aggregation in vivo. III. Effect of pentoxifylline.
Pentoxifylline (Trental) a new vasoactive agent was shown to be a powerful inhibitor of ADP and serotonin induced platelet aggregation of monkey platelets in vivo. A linear dose response curve was demonstrated between 6 and 24 mg/kg of i.v. pentoxifylline.
Adenosine Diphosphate↗
Study of platelet aggregation in vivo: IV Effect of pyrimido-pyrimidine derivatives.
Two pyrimido-pyrimidine derivatives (RA 233 and VK 744) were found effective aggregation inhibitors in vitro of human and monkey platelets and in vivo in stumptailed monkeys and chimpanzees. They also inhibited thrombotic occlusion of metal screens inserted into arteriovenous shunts.
Animals↗
Study of platelet aggregation in vivo: V effect of the antiserotonin agent cyproheptadine.
The antiserotonin agent cyproheptadine (Periactin) was shown to be an effective antagonist of in vivo platelet aggregation induced in monkeys not only with serotonin but also with ADP.
Adenosine Diphosphate↗
Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.
During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.
Adult↗
Prevention of hyaline membrane disease with plasminogen. Preliminary report of a cooperative study.
Five hundred premature infants were treated in a double blind, randomized study with intravenous plasminogen or placebo within 60 minutes of birth. There was a significant decrease in severe clinical respiratory distress, death due to hyaline membrane disease and total mortality in the plasminogen treated infants as compared to the controls.
Clinical Trials as Topic↗
Effect of galactose and sugar substitutes on blood insulin levels in normal and obese individuals.
Eighteen male patients between the ages of 25 and 50 were given on a double blind randomized basis (A) 40 gms. galactose (B) 50 gms. arabinogalactan and 0.11 gm. sodium saccharin (C) 2 gm. methyl cellulose and 0.083 gm. sodium saccharin and (D) 4 gm. galactose, all in 200 ml water. Blood glucose, galactose and insulin levels were determined during a six hour period before and after ingestion. The three first mentioned solutions tasted equally sweet, the fourth was essentially tasteless. None of these feedings altered plasma insulin or glucose levels. It appears that in contrast to other conclusions reached by earlier investigators sweet taste is unable to induce insulin secretion through neurogenic pathways.
Adult↗
Erythroid and myeloid regeneration after nitrogen mustard therapy, autologous bone marrow transplantation, and treatment with an anabolic steroid.
Stumptailed monkeys (Macaca arctoides) received a lethal nitrogen mustard injection. Autologous bone marrow reinjection resulted in survival of the majority of animals. Treatment with an anabolic steroid accelerated erythropoietic and leukopoietic recovery. This appears to be related to increased erythropoietin production and increased number of colony forming units in the bone marrow.
Animals↗
Study of platelet aggregation in vivo i. Effect of bencyclan.
A 20mu diameter pore size screen was inserted into an arterio-venous bypass system in heparinized stumptailed monkeys. ADP and serotonin injection resulted in aggregation of platelets on the screen and consecutive increase in pre-screen pressure and decrease in post-screen pressure. From these changes an "aggregation index" was calculated. Bencyclan in doses of 0.5-15 mg/kg inhibited platelet aggregation in vivo. Doses of 20 mg/kg or above showed some hemolytic effect, no other undesirable effects were seen.
Adenosine Diphosphate↗
Effect of various estrogen treatment schedules on antithrombin III levels.
Antithrombin III levels were determined in 18 normal indiviuals of both sexes, 24 pregnant women (at term), 20 patients treated with oral contraceptives and 21 postmenopausal patients treated with Premarin. There was no sex difference in antithrombin III levels in the untreated control group. Pregnant women at term had the lowest levels of antithrombin III. The second lowest values were exhibited by women on oral contraceptives. Both of these groups differed significantly (p less than 0.05) from the controls. Premarin treated postmenopausal women had somewhat lower levels of antithrombin III than controls but these were statistically not significant.
Adolescent↗
Clinical and experimental studies on adenine, various nucleosides and their analogs in hematology.
In red blood cells as well as in platelets there appears to be a decrease in adenine nucleotides during storage under blood bank conditions. This can be decreased by use of anticoagulant preservatives with higher phosphate content than the standard ACD solution, through the addition of adenine and inosine. Maintenance of higher ATP levels appears to be related to longer circulating life span after transfusion into patients in the case of red blood cells but not platelets. Inosine and more alkaline preservative medium also contribute to the maintenance of 2,3-DPG levels in red blood cells, and with it to the maintenance of normal hemoglobin dissociation curves and thus oxygen-carrying capacity. Certain nucleoside analogs may contribute to the preservation of platelets and of whole blood by their platelet-aggregation inhibitory activity. Platelet-aggregation inhibitors may also be useful in preventing thromboembolic episodes with potentially greater safety than anticoagulants.
Adenine↗
Studies on the prevention of respiratory distress syndrome of infants due to hyaline membrane disease with plasminogen.
Hyaline membrane disease (HMD) is leading single cause of death of newborn, premature infants. The "hyaline membranes" consist chiefly of fibrin. The clinical manifestation of HMD is the respiratory distress syndrome (RDS). Infants with RDS were treated with urokinase-activated human plasmin in a previous clinical trial. Survival rate was increased in the plasmin treated group as compared to the placebo recipients. However, cost and difficulty in the preparation of the enzyme made this treatment impractical. We, as well as others, have shown the premature infants lack serum plasminogen; thus they are unable to develop effective fibrinolysis and are defenseless against pulmonary fibrin deposition. Therefore, plamsinogen was tested as a possible preventive agent in RDS due to HMD. In a double blind, randomized study, infants between 1 and 2.5 kg birth weight received plasminogen or placebo shortly after birth, and were then followed for development of RDS. After 100 infants were entered into the study, the code was broken and results were evaluated to assure safety of the procedure. Among the 100 infants, 51 received placebo, 49 received plasminogen. Among the infants who received placebo, seven developed mild, and ten developed severe respiratory distress; of these ten, five died with histopathologically documented HMD. Two infants died from causes other than HMD. Among the 49 infants treated with plasminogen, 13 developed mild and three developed severe respiratory distress. There was no death due to HMD. Two deaths were due to other causes. Factors placing the infant at risk from HMD (degree of prematurity, sex, cesarean section, bleeding episodes during pregnancy, maternal diabetes) were found to be evenly distributed between control and treated groups. Since completing the first phase of the study, data of an additional 277 infants has become available. Although the code was not broken in this series, a preliminary look at mortality data in comparison with mortality data of the first series of 100 (in which the code was broken) suggests that preventive activity of plasminogen has been maintained in the second phase of the study.
Birth Weight↗
Causes of death in cancer patients.
Causes of death in the year 1970 were analyzed retrospectively on the basis of clinical and pathologic reports of 506 cases in the Roswell Park Memorial Institute and Hospital. The single major cause of death was infection (36%), which was also a contributory factor in an additional 68% of the cases. Other important causes of death were hemorrhagic and thromboembolic phenomena (18%), which also were contributory factors in an additional 43%. Organ invasion by neoplastic cells including hepatic failure was the major cause of death in 10% and was a contributory factor in 5%. Cachexia was reported as major cause of death in 1% and as contributory factor in 0.4%. Respiratory failure due to various causes (including aspiration) was the main mechanism of death in 19% and a contributory factor in 3%. Cardiovascular insufficiency was the major cause of death in 7% and a contributory factor in 3%.
Autopsy↗
Laboratory and clinical evaluation of the radiation-potentiating activity of ethyl-N-bis (2,2-dimethylethylamidinophosphoro) carbamate (AB-132).
Ethyl-N-bis (2,2-dimethylethylamidinophosphoro) carbamate (AB-132) has been shown to potentiate the effect of whole-body radiation on inhibition of splenomegaly induced by Friend leukemia virus in ICR/H Swiss mice. The combined effect of AB-132 and radiation does not appear to be related to Friend virus inhibition but seems to act on the proliferating tumor in the spleen. Nine children with advanced cancer were treated with combined administration of local radiation and systemic AB-132. Although regression of tumor was seem, no dramatic effect on survival was apparent. One case of metastatic Ewing's sarcoma showed systemic tumor response to AB-132 in addition to localized response to radiation. Bone marrow depression appeared to be the main side effect of combination therapy.
Animals↗
Thromboembolic complications of oral contraceptive therapy.
During a ten-year period, 348 women were studied for a total of 5877 patient months for changes in hematologic parameters induced by oral contraceptives. Significant increases were observed in Factors I, II, VII, VIII, IX, X and plasminogen. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. All four patients were of A or AB blood group. It appears from these data that hematologic workups may be useful in women who are about to embark on long-term oral contraceptive therapy.
Blood Cell Count↗