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Biomedical subjects

M J Doyle

Publications and source records attributed to M J Doyle.

34 records · Page 2Linked to original sources

Medication errors: 1977 to 1988. Experience in medical malpractice claims.

MIIENJ has paid $30,144,636 in indemnity from 1977 through 1988 for medical malpractice suits arising from medication errors. A review of these files revealed that patients incurred death and serious morbidity, and that several specific behavior errors accounted for the majority of patient injury. Among the damages that occurred during that time period were 88 deaths, 15 patients with profound brain damage, 15 patients who alleged that they had become addicted to medications prescribed for pain, 10 patients who required amputations of limbs, and 12 patients who suffered some degree of hearing loss or decreased visual acuity. The predominant categories where insureds incurred difficulty were in disregarding patient allergies to specific drugs (acetylsalicylic acid (aspirin), penicillin and its derivatives); prescribing drugs without consideration of the patient's medical history; failing to monitor therapy with anticoagulants, nonsteroidal anti-inflammatory drugs, digitalis derivatives, theophylline, and aminoglycoside antibiotics; antibiotic therapy; and errors in the writing of prescriptions. In order to reduce the number of patient injuries and accompanying medical malpractice suits from medication errors, the following suggestions are offered: 1. Heed the patient's warning regarding drug allergies and prescribe a substitute drug, especially if the drug is aspirin or penicillin (and derivatives) or if the patient gives a history of having asthma. If the patient gives a history of aspirin sensitivity, make certain the drug you are prescribing does not contain aspirin as one of its components. Often physicians stated that they were not aware that aspirin was contained in the drug they prescribed for patients with a documented allergy to aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vivo assessment of precursor induced prostaglandin release within the rat gastric lumen.

Gastroprotection associated with the intragastric administration of prostaglandin (PG) precursor fatty acids such as linoleic (LA), gamma-linolenic (GLA), and arachidonic acid (AA) has been reported to be mediated via their conversion to PGs. This report examines the relationship between gastroprotection and the extent/rate of PG-release in rats intragastrically administered PG biosynthetic precursors: LA, AA, dihomo-gamma-linolenic acid (DHGL) or oleic acid (OA, a nonprecursor fatty acid). At various times following intragastric administration of a fatty acid, gastric fluid was collected, extracted, chromatographed, and assayed for PGE1 or PGE2 by specific radioimmunoassay. AA and DHGL dose dependently elevated gastric PGE2 and PGE1 levels, respectively. Maximal PGE elevation, 200-400 ng/stomach, was over 400-fold above basal values, and observed within 5-10 minutes of administration. Conversely, OA and LA elicited only a minor (2-10 fold) stimulation of PGE release. In contrast to effects on PG release, all four fatty acids protected the gastric mucosa against macroscopic damage induced by ethanol. The apparent rank order of potency was AA greater than DHGL = LA greater than OA (the difference in potency between DHGL or LA and OA was not significant). Since LA and OA (a nonprecursor) only marginally elevated lumenal PGs relative to DHGL or AA, yet were equally efficacious in the gastroprotection assay, it is likely that other fatty acid-related mechanisms play an important role in protecting the stomach against ethanol-induced injury.

Animals↗

Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity.

The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. These results suggest that TNF may play an autocrine regulatory role in concert with lymphokines in macrophage-mediated host defense against malignant neoplasia.

Animals↗

Effect of anti-thrombospondin antibodies on the hemagglutination activities of the endogenous platelet lectin and thrombospondin.

The proposal that thrombospondin is the endogenous platelet lectin was evaluated using antisera and monoclonal antibodies to thrombospondin. The platelet-bound hemagglutinin activity of human platelets stimulated with A23187 was inhibited by rabbit anti-thrombospondin sera and by a monoclonal anti-thrombospondin IgG. A second monoclonal IgG did not inhibit platelet-bound agglutinin activity. Preparations of purified platelet thrombospondin differed in their hemagglutination activities. The hemagglutination activity of an active preparation of thrombospondin was inhibited by the monoclonal antibody that inhibited platelet-bound lectin activity. The hemagglutination activity of an almost inactive preparation of thrombospondin was enhanced by the anti-thrombospondin monoclonal antibody that did not block platelet-bound lectin activity. The results demonstrate that expression of the platelet-bound form of the endogenous lectin is thrombospondin-dependent and suggest that thrombospondin must become part of a larger complex, either by binding to the platelet surface or by becoming aggregated in solution, before hemagglutination activity can be expressed.

Antibodies, Monoclonal↗

Cultured human fibroblasts synthesize and secrete thrombospondin and incorporate it into extracellular matrix.

Thrombospondin, a major glycoprotein released from alpha granules of thrombin-stimulated platelets, is a disulfide-bonded trimer of 160-kilodalton subunits. Cultured human foreskin and fetal lung fibroblasts secreted thrombospondin (determined by enzyme-linked immunosorbent assay) into the culture medium in a time-dependent manner (15.7 and 5.8 micrograms per 10(6) cells per 24 hr, respectively); secretion was blocked by cycloheximide. [3H]Thrombospondin was isolated from [3H]leucine-labeled fibroblast postculture medium and from cell layers with rabbit polyclonal or mouse monoclonal anti-thrombospondin coupled to staphylococcal protein A-Sepharose. The immunologically isolated [3H]thrombospondin migrated in NaDodSO4/polyacrylamide gels with purified marker platelet thrombospondin both with and without reduction. Immunofluorescence microscopy using rabbit polyclonal and mouse monoclonal anti-thrombospondin antibodies localized thrombospondin to the fibrillar extracellular matrix surrounding the cells. Thus, cultured human fibroblasts secrete thrombospondin and incorporate it into the extracellular matrix.

Cells, Cultured↗

Synthesis and secretion of thrombospondin by cultured human endothelial cells.

Thrombospondin, the major glycoprotein released from alpha-granules of thrombin-stimulated platelets, is a disulfide-bonded trimer of 160 kilodalton subunits and apparently functions as a platelet lectin. Because cultured human umbilical vein endothelial cells synthesize and secrete a glycoprotein (GP-160) which is a disulfide-bonded multimer of 160 kdalton subunits, the possibility that GP-160 is thrombospondin was investigated. Tritiated GP-160 could be immunoisolated from [3H]leucine-labeled endothelial cell postculture medium using a rabbit antiserum to human platelet thrombospondin. Thrombospondin and GP-160 comigrated in two different two-dimensional electrophoretic systems. Both proteins are disulfide-bonded trimers of acidic 160-kdalton subunits. A competitive radioimmunoassay for binding of 125I-thrombospondin to the rabbit antibodies indicated that 49 micrograms of thrombospondin antigen per 10(6) confluent endothelial cells accumulated in postculture medium over 24 h. Thus, endothelial cells secrete large amounts of a glycoprotein that is identical or very similar to platelet thrombospondin.

Cells, Cultured↗

Quantification of hyperbaric oxygen-induced toxicity utilizing a malarial system.

This study was undertaken in recognition of the need to develop quantitative systems to evaluate the toxicity associated with hyperbaric oxygen (HBO) exposure. Malaria-infected (P. berghei berghei) mice were briefly exposed to 100% oxygen at 3 ATA on day 10 of infection. At 25, 48, and 72 h thereafter, the levels of circulating erythrcytes and percent parasitized RBC were monitored and compared to those of infected non-exposed controls. The total erythrocyte counts of the infected HBO-exposed and non-exposed mice did not differ significantly. In contrast, percent parasitized cells in the oxygen-exposed mice were lowered to 55-60% control values at 24, 48, and 72 h. The mechanism of this difference needs further study, but we believe that P. berghei-infected erythrocytes are preferentially hemolyzed as a consequence of HBO exposure. this mode system is useful in the study of HBO-induced toxicity because of its high degree of selectivity and sensitivity and its amenability to strict quantification over a period of at least several days.

Animals↗

Biochemical changes in developmentally retarded Xenopus laevis larvae. I. The lens crystallin transition.

Premetamorphic tadpoles of Xenopus laevis reared in water containing 0.01% propylthiouracil are developmentally retarded and metamorphosis is prevented. When uncrowded, they continue to grow to a giant size. Moderate crowding leads to a slower rate of growth. Thus morphologically premetamorphic tadpoles were produced with lens diameters appropriate to either normal premetamorphic, climactic or post-metamorphic animals. The lens crystallins of such tadpoles have been separated by immunoelectrophoresis and polyacrylamide gel electrophoresis. The crystallin pattern was correlated with lens diameter rather than with body stage. Giant retarded larvae possessed crystallin patterns identical to those or normal adults. The thyroid antagonist propylthiouracil is therefore unable to prevent the lens crystallin transition, the beginning of which is normally temporally correlated with metamorphosis.

Animals↗