PubMed HealthSearch

Biomedical subjects

M Jeffries

Publications and source records attributed to M Jeffries.

9 recordsLinked to original sources

Prevention of reperfusion injury in surgically induced gastric dilatation-volvulus in dogs.

Canine gastric dilatation-volvulus (GDV) is a naturally acquired condition of large-breed dogs primarily and is associated with high mortality. The clinical course suggests that reperfusion injury may be important in the pathogenesis of GDV. To evaluate the role of xanthine oxidase and iron-dependent lipid peroxidation (which are purported mechanisms of reperfusion injury) in the pathogenesis of GDV-related mortality, we created experimental GDV in 21 dogs. These dogs were then treated with either allopurinol (a xanthine oxidase inhibitor), U74006F (an experimental lipid peroxidation inhibitor), or saline solution (NaCl, 0.85%). Three of 8 dogs died in the allopurinol-treated group, none of 5 died in the U74006F-treated group, and 4 of 8 died in the saline solution-treated group. Tissue malondialdehyde concentration, a nonspecific indicator of lipid peroxidation, was significantly (P less than 0.05) greater in the duodenum, jejunum, colon, liver, and pancreas of the saline-solution treated and allopurinol-treated dogs than in the same tissues of the U74006F-treated dogs after surgical correction of the GDV (ie, during reperfusion), compared with malondialdehyde concentrations determined before inducing GDV. The results of this study support the concept that lipid peroxidation associated with reperfusion injury is important in the pathogenesis and high mortality of canine GDV. Furthermore, this lipid peroxidation and mortality may be preventable by appropriate and timely treatment.

Allopurinol

Characterization of nonactivated and activated glucocorticoid-receptor complexes from intact rat thymus cells.

In cells exposed to glucocorticoids at 37 degrees C activated glucocorticoid-receptor complexes (complexes with affinity for nuclei and DNA) are formed after nonactivated complexes. Activation thus appears to be an obligatory physiological process. To investigate this process we have characterized cytoplasmic complexes formed in rat thymocytes at 0 and 37 degrees C. Complexes in cytosols stabilized with molybdate were analyzed by sucrose gradient centrifugation and by chromatography on DNA-cellulose, DEAE-cellulose, and agarose gels. Two major complexes were observed: the nonactivated complex, eluted from DEAE at approximately 200 mM KCl, was formed at 0 and 37 degrees C, gave S20,w = 9.2 S, Stokes radius = 8.3 nm, and calculated Mr = 330,000; the activated complex, eluted from DEAE at approximately 50 mM KCl, appeared only at 37 degrees C, gave S20,w = 4.8 S, Stokes radius = 5.0 nm, and Mr = 100,000. A third, minor complex, probably mero-receptor, which appeared mainly at 37 degrees C, bound to neither DNA nor DEAE, and gave S20,w = 2.9 S, Stokes radius = 2.3 nm, and Mr = 27,000. With three small columns in series (DNA-cellulose, DEAE-cellulose and hydroxylapatite), the three complexes can be separated in 5-10 min. By this method we have examined the stability of complexes under our conditions. We conclude that in intact thymus cells glucocorticoid-receptor complexes occur principally in two forms, nonactivated and activated, and that activation is accompanied by a large reduction in size. The origin of the mero-receptor complex remains uncertain.

Animals

The changing role of "second-look" laparotomy in the management of epithelial carcinoma of the ovary.

Thirty-seven of 137 patients had a "second-look" laparotomy in the course of their management of carcinoma of the ovary. Patients were stratified according to three indications: (1) evaluation of disease with intent of stopping therapy, (2) assessment of signs of recurrent or persistent disease with a view to debulking tumor mass and changing chemotherapy, and (3) further tumor resection following cis-platinum combination therapy and determination of further chemotherapeutic agents. "Second-look" laparotomy may be performed after a shorter time interval when combination therapy is given because of the dose-limiting side effects of some of these agents and a more aggressive surgical approach in debulking tumors. At the time of laparotomy, cytologic testing is performed on the peritoneal fluid, and only areas suspicious for malignancy are biopsied. Thirteen percent of patients with no evidence of disease at "second-look" laparotomy developed recurrent disease. Twenty-nine percent of patients classified as clinically free of disease had malignancy present at the time of operation. Continued routine use of "second-look" laparotomy after appropriate chemotherapy is recommended.

Adenocarcinoma