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Biomedical subjects

J L Ambrus

Publications and source records attributed to J L Ambrus.

At least 145 records · Page 8Linked to original sources

Effect of sodium meclofenamate on radiation-induced esophagitis and cystitis.

Stumptailed monkeys (Macaca arctoides) received 2000 rad irradiation to the upper half of the esophagus and to the bladder by a 6-MEV linear accelerator. Endoscopy and biopsy was obtained from these organs weekly for 3 weeks. At the end of this period, the animals were autopsied and histopathologic examination undertaken. Sodium meclofenamate in doses of 5-20 mg/kg/day p.os was found effective in reducing or preventing radiation induced esophagitis and cystitis.

Animals↗

Desensitization to experimental asthma with 48/80.

The mast cell disintegrating histamine releaser, compound 48/80, given daily for 5 days by aerosol to guinea pigs produced relative resistance to 48/80 induced asthma, but not to histamine induced asthma. After 3 days of rest, sensitivity to the respiratory effects of 48/80 returned to baseline level. It was thought that the effects observed were due to depletion of pulmonary mast cells or their asthma mediators and regeneration after a period of rest.

Aerosols↗

Antineoplastic effect of the pyrimido-pyrimidine derivative: RA 233.

A number of normal and neoplastic human cell lines in culture were studied by cell count and 3H thymidine incorporation for growth inhibitory effect by the pyrimido-pyrimidine derivative RA-233 (mopidamole). There was more inhibition when the drug was added to the culture in the lag phase than in the logarithmic growth phase. There was more inhibition (particularly at low doses) of the neoplastic cell lines than of the non-neoplastic cell lines.

Antineoplastic Agents↗

Prognostic parameters in recurrent malignant melanoma.

In 361 patients with recurrent malignant melanoma, the clinical stage was the strongest determinant of subsequent survival (P less than 0.01). In Stage IV, the number of initial, distinct lesions was important. Patients presenting with a single metastatic nodule had median survival ten months, whereas those with two or more metastatic nodules had median survival 6.9 months (P less than 0.05). The length of disease-free interval from excision of the primary to recurrence correlated consistently with subsequent survival in patients with regional lymph node metastases. Those with disease-free interval less than one year had median survival 15.8 months with 16% surviving at five years, while those with interval one year or longer had median survival 23.7 months with 30% surviving at five years (P less than 0.05). In Stage IV, the correlation of survival with disease-free interval became significant only with 24 months as the demarcation point of length of disease-free interval. Age and sex affected the disease-free interval, but not survival after recurrence.

Adolescent↗

The role of fibrin adhesive in vascular surgery.

Fibrin Seal (FS) (a natural adhesive material composed of fibrinogen, cold insoluble globulin, factor XIII, platelet growth factor, antiplasmin thrombin, and calcium chloride) was utilized in the construction of vascular anastomosis of the femoral artery of mongrel dogs. A significant decrease in the number of sutures necessary to achieve adequate anastomosis and minimize the likelihood of postoperative bleeding was noted. There was no long-term increase in tissue reaction or decrease in arterial patency. On the basis of these preliminary results the role of FS as a hemostatic agent in vascular and especially microvascular surgery warrants further investigation.

Animals↗

The role of the tissue adhesive fibrin seal (FS) in esophageal anastomoses.

Following surgical removal of esophageal tumors, leakage and mediastinitis is a frequent and often fatal complication. A new method has been developed to seal suture lines in the esophagus with preparations containing fibrinogen, cold insoluble globulin, factor XIII, antiplasmin, platelet growth factor, thrombin, and calcium chloride. In experimental animals operated on by standard methods, esophageal leakage developed in 50% of the animals and death in 40%. By contrast, in treated animals, esophageal leak and death developed in only 20%. More adhesions were found in treated animals than in control animals.

Animals↗

Studies on osteoporosis X. Effect of estrogen-progestin combination on heparin-induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St(Ha) female mice. As 99% of body calcium is in bone, loss of calcium was used as an index of bone loss (osteoporosis). Heparin (500 U/kg b.i.d. caused bone loss in 3 months. Premarin (2 mg/kg q.d.) or norethindrone (40 mg/kg q.d.) alone prevented this osteoporosis. A Premarin-norethindrone combination (2 mg - 10 mg q.d. respectively) appeared to be somewhat more effective than either agent alone, but this difference was not significant at the 5% level. Combinations of estrogen and progestins may prevent metabolic bone disease at the same time reducing the danger of estrogen induced neoplasia.

Animals↗

Studies on osteoporoses. XI. Effects of a methylxanthine derivative. A preliminary report.

Heparin (500 U/kg s.c. B.I.D.) induced significant osteoporosis in C3H/St(Ha) female mice after 3 months of treatment. Pentoxifylline (12 mg/kg i.m. B.I.D.) prevented this experimental osteoporosis. Osteoporosis was measured by in vivo neutron activation analysis and results were confirmed by atomic absorption spectroscopy. Pentoxifylline (0.1-100 microgram/ml) increased calcium uptake and cAMP production in osteoblast-like bone cells isolated from fetal Sprague-Dawley rats. Theoretical implications for osteoblast control of bone resorption are discussed.

Animals↗

Clinical experience with prostaglandin E1 in the treatment of arteriosclerosis obliterans. A preliminary report.

Eleven patients with severe arteriosclerotic disease of the lower extremities who were unsuitable for surgical bypass procedures or who had surgical bypass failure have been treated with prostaglandin E1. The patients all responded well to the prostaglandin treatment, except for one patient who required an above the knee amputation. Subjective evidence of pain and swelling disappeared and the patients' narcotic requirements were reduced. In those patients who had ulcers of the lower extremities, healing was promoted spontaneously or together with skin grafting. Side effects experienced by some patients, such as diarrhea, joint pain and swelling of the extremities, did not warrant discontinuation of drug therapy. There were no changes in blood chemistry. There was marked inhibition of platelet aggregation, and moderate inhibition of red cell deformability.

Aged↗

Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents.

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.

Animals↗

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.

Ammonia-Lyases↗

Protection of normal tissues with 2-aminoethylisothiouronium during local pelvic radiation in monkeys.

Intestinal and bladder injury are the main limiting factors to radiation therapy in patients with pelvic neoplasms. 2-Amino-ethylisothiouronium (AET) is a radiation-protective agent when given systemically but absorbs poorly from the intestines. Accordingly, it was explored for the local protection of the bowel and bladder during radiation to the pelvis. Radiation localized to the pelvis in various high fractionated doses and various schedules was applied to pairs of stumptailed monkeys (Macaca arctoides): one was always a control; and the other was treated with AET. AET was applied to the bladder through a catheter and to the rectum with a cotton tampon during the time of radiation. After radiation, AET was removed by repeated washings. Control animals developed hemorrhage, diarrhea, and emaciation and died at various times after completion of the radiation course; biopsy of rectal mucosa showed severe radiation damage. AET-treated animals had only occult blood in the stools and suffered slight weight loss; rectal biopsies showed normal tissues 2 weeks after radiation.

Animals↗

Renal prostaglandin E2 biosynthesis: dependence on angiotensin II.

To study the interaction of the prohypertensive renin-angiotensin axis with the antihypertensive renal prostaglandins, angiotensin-converting enzyme inhibition (captopril and teprotide) and angiotensin blockade (Sar1-Ile8-AII) were produced in rabbits in vivo and renal slice prostaglandin E2 was measured in vitro after 30 minutes of incubation in Krebs-Ringer HCO3- buffer. In rabbits with angiotensin-converting enzyme inhibition, de novo prostaglandin E2 synthesis decreased in cortical, outer medullary and papillary slices by 85, 52 and 47 percent, respectively. Similar degrees of inhibition were observed with angiotensin blockade. It is concluded that renal prostaglandin E2 synthesis is angiotensin II dependent under these conditions. This finding suggests that any increase in the prohypertensive antinatriuretic renin-angiotensin axis may be associated with a secondary increase in renal prostaglandin E2 which may be acting in an antihypertensive natriuretic compensatory fashion.

1-Sarcosine-8-Isoleucine Angiotensin II↗

The application of tissue adhesives in small bowel anastomoses.

One layer everted end-to-end anastomosis was performed on the small bowel of mongrel dogs. Cultures of Serratia marcescens were injected into the lumen. Twenty-four hours later the animals were reexplored, and peritoneal cultures were observed. In animals where Fibrin Seal (consisting of fibrinogen, cold insoluble globulin, factor XIII, platelet growth factor, antiplasmin, thrombin, and calcium chloride) was applied to the suture line, negative cultures were found except for two experiments in which dehiscence or contamination from the Serratia injection site occurred.

Animals↗

Attempts to bypass the need for splenectomy in splenic injury.

Within the last decade spleen salvage has been a controversial issue. Only recently, with the advances and utilization of modern technology in surgery, spurred by a better understanding of this immunologically important organ, preservation has become a reality. Numerous approaches have been suggested. Reported is a simple method of applying a new agent, Fibrin Seal (FS), to control hemorrhage from splenic injury. In a controlled study using 14 mongrel dogs, it is compared to the hemostatic ability of cryoprecipitate with thrombin and Avitene. FS is an adhesive material with hemostatic qualities consisting of fibrinogen, factor XIII, antiplasmin, cold-insoluble globulin, and platelet growth factor. FS appears to have cohesive and adhesive properties that result in more efficient hemostasis than the controls. FS conforms to the spleen surface, allowing manipulation of the organ without dislodgement of the coagulum. Follow-up laparotomy showed minimal tissue reaction. On the basis of these data, consideration of FS as an important hemostatic agent warrants clinical investigation.

Animals↗