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Biomedical subjects

D Ross

Publications and source records attributed to D Ross.

At least 271 records · Page 15Linked to original sources

Coronary artery surgery with patient's lungs as oxygenator.

The use of the patient's own lungs as oxygenator was assessed during coronary artery bypass grafting in 20 patients. This technique maintained the circulation and provides excellent oxygenation, and the lungs did not intrude on the operative field. Blood damage as assessed by platelet function and lung sequestration was less than that reported with other forms of bypass. No microbubbles were produced, since there was no artificial blood/air interface. Complement activation, as assessed by amount of white-cell sequestration in the lungs, was also lower than that reported in other forms of bypass. There were no major complications attributable to the technique. Apart from being substantially cheaper than conventional cardiopulmonary bypass, the use of the patient's lungs as oxygenator offers the potential advantage of reduced trauma to the blood and merits further consideration.

Adult↗

Role of redox cycling and lipid peroxidation in bipyridyl herbicide cytotoxicity. Studies with a compromised isolated hepatocyte model system.

The role of active oxygen species and lipid peroxidation in the toxic effects of diquat, paraquat and other bipyridyl herbicides remains controversial. In vitro studies have shown that these compounds are potent generators of active oxygen species by redox cycling and that they stimulate lipid peroxidation. In vivo studies have failed, however, to show clear evidence of lipid peroxidation resulting from toxic exposures to these compounds. We have directly compared the abilities of three bipyridyl herbicides, diquat (DQ), paraquat (PQ) and benzyl viologen (BV), to generate superoxide anion radical (O2-.) in rat liver microsomes and H2O2 in hepatocytes and correlated this with their relative toxicities to a compromised isolated hepatocyte system. DQ was the most potent generator of O2-. and H2O2, being slightly more potent than BV and much better than PQ. This ability of the bipyridyls to generate active oxygen was positively correlated with the ability to induce toxicity in hepatocytes pretreated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) to inhibit their glutathione reductase activity, i.e. DQ greater than BV greater than PQ. DQ caused a rapid depletion of cellular GSH and a concomitant increase in GSSG in this system. Toxicity, measured as loss of plasma membrane integrity, was pronounced after only 30-60 min of incubation and was accompanied by a significant increase in lipid peroxidation. The onset of lipid peroxidation could not be separated temporally from the expression of toxicity. However, the total inhibition of lipid peroxidation by the antioxidants Trolox C, promethazine and N,N'-diphenyl-p-phenylenediamine only delayed toxicity, indicating that, even though lipid peroxidation may play some role in enhancing bipyridyl herbicide toxicity, it is not essential for the toxicity to manifest itself.

Animals↗

The role of oxidative processes in the cytotoxicity of substituted 1,4-naphthoquinones in isolated hepatocytes.

In order to clarify the role of oxidative processes in cytotoxicity we have studied the metabolism and toxicity of 2-methyl-1,4-naphthoquinone (menadione) and its 2,3 dimethyl (DMNQ) and 2,3 diethyl (DENQ) analogs in isolated rat hepatocytes. The two analogs, unlike menadione, cannot alkylate nucleophiles directly and were considerably less toxic than menadione. This decreased toxicity was consistent with the inability of DMNQ and DENQ to alkylate but we also found them to undergo lower rates of redox cycling in hepatocytes and a higher ratio of two electron as opposed to one electron reduction relative to menadione. Thus, facile analysis of the respective roles of alkylation and oxidation in cytotoxicity was not possible using these compounds. In hepatocytes pretreated with bischloroethyl-nitrosourea (BCNU) to inhibit glutathione reductase, all three naphthoquinones caused a potentiation of reduced glutathione (GSH) removal/oxidized glutathione (GSSG) generation and cytotoxicity relative to that observed in control cells. These data show that inhibition of hepatocyte glutathione reductase by BCNU results in enhanced naphthoquinone-induced oxidative challenge and subsequent cellular toxicity. That DMNQ and DENQ are cytotoxic, albeit at high concentrations, and that this cytotoxicity is potentiated by BCNU pretreatment suggest that oxidative processes alone can be a determinant of cytotoxicity.

Alkylation↗

Blood gas changes and hypophosphatemia in lactate-induced panic.

Alkalosis is prominent among the many physiologic and biochemical effects of sodium lactate infusion. Though this is partially due to the conversion of lactate to bicarbonate, the metabolic component, it may also be secondary to hyperventilation before and during the infusion, the respiratory component. We analyzed pH, carbon dioxide pressure, bicarbonate, and inorganic phosphate from patients with panic disorder and agoraphobia with panic attacks and from normal controls both before and during lactate infusion. Our findings extend earlier work demonstrating that many such patients are chronic hyperventilators. Both metabolic and respiratory alkalosis develop in all subjects during lactate infusion, but only hyperventilation-induced hypocapnia differentiates patients at the point of lactate-induced panic from nonpanicking patients and normal controls. Finally, low inorganic phosphate levels at baseline appear associated with patients who will panic during the subsequent lactate infusion. This last unexpected finding may reflect hyperventilation or an abnormality in intracellular glycolysis.

Adult↗

Muir-Torre syndrome.

The patient with sebaceous skin tumors and visceral malignancies, Muir-Torre syndrome, is presented. The documentation of tumors in 8 of 13 members in her kindred supports the concept that this syndrome represents a cancer-disposing phenotype.

Adenocarcinoma↗

Mechanism and relevance of glutathione mutagenicity.

The ubiquitous tripeptide glutathione (GSH) has previously been shown to be mutagenic to Salmonella typhimurium TA100 when incubated with kidney subcellular fractions at physiological concentrations (Glatt et al., 1983). Here we report that the mutagenic effect of GSH can be inhibited by the use of the gamma-glutamyl-transpeptidase (gamma-GT) inhibitor anthglutin and by the metal chelators bathocuproine, EDTA and diethyldithiocarbamate. As the chelating agents did not inhibit gamma-GT activity this suggested that the mechanism underlying the mutagenic effect of GSH was at least a two-step process, dependent upon the cleavage of GSH by gamma-GT and the presence of either free transition metals or those contained in enzymes such as glutathione oxidase. As gamma-GT is located on the outer surface of kidney tubule cells and is therefore exposed to relatively low concentrations of GSH, and the precise physiological control of levels of transition metals, this mechanism is unlikely to occur in vivo.

Animals↗

An improved technique for long saphenous vein harvesting for coronary revascularization.

A prospective study was undertaken to assess the functional quality of long saphenous vein for coronary revascularization when it has been harvested by means of multiple small incisions and use of the Mayo "stripper." This avoids a "long cut" and the major wound problems commonly associated with it. Between January, 1979, and July, 1984, 2,439 patients underwent coronary artery bypass graft with long saphenous vein harvested by this technique. No major wound problems occurred, and minor wound problems were seen in only 23 patients (0.9%). Vein quality was assessed by histological studies of veins, postoperative graft angiography, and exercise testing. Both light electron microscopy and scanning electron microscopy demonstrated that the vein was of good quality and that the intima had been preserved. Postoperative graft angiography and exercise testing confirmed high patency rates for the vein grafts (93%). Vein harvesting with this technique is easy, gives good quality vein, both morphologically and functionally, for grafting, is associated with a minimum of wound problems, and has cosmetically superior results.

Adult↗

The sit-up position for breast reconstruction.

For breast reconstruction, we have found that breast symmetry can be created optimally when the patient is brought to a totally upright position with the trunk vertical and perpendicular to the floor. The size of the opposite breast can better be appreciated. Nipple and areola position can be determined accurately even with the patient asleep if she is brought to the upright position. The safety of the upright positioning is documented in our series but depends on planning with the anesthesiologist preoperatively and allowing time to move the patient cautiously. An anesthesia technique for intraoperative vertical positioning is reported.

Adult↗

Long saphenous vein harvesting.

There is described an easy and rapid technique using the Mayo Vein Stripper to facilitate safe harvesting of the long saphenous vein for vascular reconstruction. It provides good quality vein and a superior cosmetic result without wound complications.

Coronary Artery Bypass↗

Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase.

The oxidation of phenol catalyzed by human myeloperoxidase and horseradish peroxidase resulted in extensive binding of phenol-derived metabolites to boiled rat liver protein. This binding paralleled closely the removal of phenol from the incubations and was inhibited from 83 to 99% by the addition of the antioxidants, ascorbate and glutathione, suggesting that metabolism and binding were occurring via a one-electron oxidation pathway. Metabolic studies employing both human myeloperoxidase and horseradish peroxidase resulted in the identification of 4,4'-biphenol and diphenoquinone as the principal identifiable metabolites. The addition of reduced glutathione to incubations containing horseradish peroxidase resulted in the formation of two conjugate species. These conjugate species were identified by fast atom bombardment mass spectrometry to be glutathione conjugates of diphenoquinone. The major gluthathione conjugate was identified as 3-(glutathion-S-yl)-4,4'-biphenol by NMR spectroscopy. These results suggest that the formation of highly reactive species through the peroxidase-mediated metabolism of phenol and other phenolic compounds could play an important role in the hematopoietic toxicity observed during chronic benzene exposure.

Biotransformation↗

Effects of antidepressant medication on sexual function: a controlled study.

There has been little systematic study of the types of sexual dysfunction produced by antidepressant medication or of the frequency with which this type of adverse effect occurs. The authors report results of a double-blind study in which the effects of imipramine, phenelzine, and placebo on specific aspects of sexual function were assessed in depressed outpatients before and after 6 weeks of treatment. Both active treatments were associated with a high incidence of adverse changes in sexual function and produced significantly more adverse effects on sexual function than placebo. Orgasm and ejaculation were impaired to a greater extent than erection. Adverse sexual function changes secondary to antidepressant medication occurred frequently in both men and women, although men reported a higher incidence. Antidepressant-related sexual dysfunction may be of clinical importance for medication compliance in view of current recommendations that antidepressants be administered for longer periods as maintenance therapy or for prophylaxis.

Adult↗