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Biomedical subjects

M E Murphy

Publications and source records attributed to M E Murphy.

87 records · Page 5Linked to original sources

Free radicals: a potential pathogenic mechanism in inherited muscular dystrophy.

Despite years of intensive work, the biochemical defect responsible for the pathogenesis of inherited muscular dystrophy has not been identified either in humans or animal models. This review examines evidence in support of the hypothesis that free radicals may be responsible for muscle degeneration in this disorder. A variety of cellular abnormalities noted in dystrophic muscles can be accounted for by free radical mediated damage. In addition, chemical by-products associated with free radical damage are found in dystrophic muscle tissue from humans and animals with this disease. Various enzymatic antioxidant systems can be enhanced as a normal cellular response to oxidative stress, and such changes are seen both in dystrophic muscle cells and certain other tissues of dystrophic animals. An increased level of free radical damage would follow from either: enhanced production of free radical species, or a deficient component of the cellular antioxidant system, such as vitamin E. The free radical hypothesis of muscular dystrophy can account for data supporting several alternative theories of the pathogenesis of this disease, as well as other observations which have not previously been explained.

Calcium↗

Activities of antioxidant enzymes in muscle, liver and lung of chickens with inherited muscular dystrophy.

An inherited form of muscular dystrophy in chickens has been used as a model of Duchenne muscular dystrophy. The pectoralis major muscle of chickens with this disease showed a significantly elevated activity of catalase (CAT) one day after hatching, and by 7 days showed elevated superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione-S-transferase (GST) activities. Increases were also found in tissues of the dystrophic birds that, unlike the pectoralis muscle, are considered to be unaffected by the pathology of muscular dystrophy. The soleus muscle contained significantly increased levels of SOD and GPX in 1 and 7 day old chickens, and increased GST in 1, 14, and 28 day old birds. CAT was significantly increased in liver from 1 and 7 day old chickens, while GPX was increased in lung from 1, 7 and 14 day old birds. These results support the possibility that excess oxygen free-radicals or altered cellular antioxidant defenses play some role in the pathogenesis of muscular dystrophy.

Animals↗

Antacid aspiration in rabbits: a comparison of Mylanta and Bicitra.

The effects of aspiration of (a) 2 ml of Mylanta (a particulate antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (b) 2 ml of half-strength Bicitra (a soluble antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (c) 4 ml of hydrochloric acid (pH 1.5), and (d) 4 ml of normal saline (pH 6.5) on arterial blood gas tensions and lung pathology were compared in anesthetized rabbits. PaO2 decreased similarly in all animals 15 minutes after aspiration, but recovered to normal levels 4 hours after aspiration of saline and 48 hours after aspiration of Bicitra. PaO2 remained depressed after aspiration of Mylanta and HCl. Gross and microscopic evidence of lung injury was most severe in animals that aspirated Mylanta. One animal died 8 hours after aspiration of Mylanta.

Aluminum Hydroxide↗

Endothelial response to venous injury.

This investigation characterized venous endothelial healing after surgical manipulation. Procedures were performed on jugular and femoral veins in 21 mongrel dogs without systemic anticoagulation. Veins were harvested at varying intervals and vessel structure evaluated with light, transmission, and scanning electron microscopy. Veins that were mobilized or stripped of adventitia demonstrated 25% to 50% endothelial loss at one hour. Endothelial damage was rapidly repaired with complete healing observed in some veins at 48 hours. Tourniquets and clamps resulted in prominent medial and endothelial injury at occlusion sites. Eighteen of 24 transected veins remained patent for the study period. Endothelial healing was unaffected by tension at anastomoses. These observations confirm that venous endothelium receives nutrition by luminal diffusion. The healing process of venous anastomoses is characterized by an early fibrin sleeve sealing the anastomotic site; endothelial bridging of defects can be noticeably delayed by excessive fibrin deposition.

Animals↗

An ultrastructural study of developing extracellular matrix in vitelline blood vessels of the early chick embryo.

This investigation was designed to describe the morphological events in embryonic development of peripheral blood vessels (vasculogenesis) and to relate this process to the appearance of extracellular matrix (ECM) during growth and maturation of these tissues. Extraembryonic vitelline vessels of the early chick embryo were chosen for this study and light, transmission, and scanning electron microscopy were carried out on vessels excised from chick embryos (Hamburger-Hamilton stages 8 through 23). Our data show that early (stage 10) vessels are composed of two distinct epithelial layers, an inner layer of presumptive endothelium surrounded by a layer of splanchnopleuric mesoderm. During development, the inner layer gives rise to mature vascular endothelium while splanchnopleuric mesoderm differentiates to form primitive vascular smooth muscle. Ultrastructural studies show the presence of collagen and basal lamina in the extracellular space between these two layers during initiation of endothelial and smooth muscle cytodifferentiation. Furthermore, ruthenium red-positive material is present on basal surfaces of developing vascular endothelium at this time, indicating possible glycosaminoglycans (GAG) or other polyanionic components of the ECM. These data suggest that the sequential production of basal lamina, collagen (s), and/or GAG's by developing peripheral vessel wall epithelia may be critical to their final differentiation.

Animals↗

Organic compounds in lunar samples: pyrolysis products, hydrocarbons, amino acids.

Lunar fines and a chip from inside a rock pyrolyzed in helium at 700 degrees C gave methane, other gases, and aromatic hydrocarbons. Benzene/methanol extracts of fines yielded traces of high molecular weight alkanes and sulfur. Traces of glycine, alanine, ethanolamine, and urea were found in aqueous extracts. Biological controls and a terrestrial rock, dunite, subjected to exhaust from the lunar module descent engine showed a different amino acid distribution. Interpretation of the origin of the carbon compounds requires extreme care, because of possible contamination acquired during initial sample processing.

Amino Acids↗

Antioxidant-micronutrients and HIV infection.

We measured plasma levels of all the antioxidant-micronutrients in subjects with HIV infection and controls. Plasma levels of all the carotenoids, including lutein, cryptoxanthin, lycopene, alpha-carotene and beta-carotene as well as vitamins A, C and E and cholesterol were assayed in 35 subjects with HIV infection and 38 controls. We found a significant depletion of all the carotenoids (P < 0.001) and vitamin C (P < 0.01) and cholesterol (P < 0.001) but not vitamins A or E in HIV-infected subjects. Further analysis of the HIV-infected subjects revealed that plasma levels of 4 of the groups of carotenoids and cholesterol were correlated with CD4 count but that beta-carotene and vitamins A, C and E were not. These results are reviewed in the light of the published literature and we conclude that these abnormalities of antioxidant-micronutrients are likely to reflect a metabolic phenomenon associated with HIV infection. However, an additional contribution to these deficiencies from malabsorption later in HIV disease cannot be ruled out.

Adult↗

Combined benchmarking of hospital outcomes and utilization.

A strong case is made for developing quantitative benchmarks for hospital outcomes as well as utilization that includes both acute care re-admissions and lengths of stay. A number of hospitals in two distinctly different geographic health care environments [CA and NY] are studied as to the differences in outcomes and utilization for three of the most common high-cost DRGs. Unscheduled hospital readmissions (within 30 days of initial discharge) were employed as outcome indicators because they reflect both the quality of acute care and the need for case management in the post-discharge period. Benchmark targets were established for patients with a diagnosis of congestive heart failure, acute MI treated medically, or COPD using scattergrams that showed each hospital's mean acute LOS on the x axis and the re-admission rates on the y axis. "Benchmarks were identified as those points with the lowest values for both indicators, as demonstrated by points that were closest to the intersection of the two axes."

Benchmarking↗

Improving performance in diabetes care: a multicomponent intervention.

CONTEXT: Compliance with recommendations from the American Diabetes Association for management of patients with diabetes is not optimal. Changing physician practice patterns with provider-focused interventions can be difficult. We report results after implementation of a type 2 diabetes mellitus guideline. OBJECTIVE: To increase the annual rate of microalbumin/urine protein testing, dilated eye examinations, and foot examinations for patients with diabetes and to reduce overall levels of hemoglobin A1c (Hb A1c). DESIGN: Before-after study. INTERVENTION: From April 1996 to June 1998, a guideline on type 2 diabetes mellitus was implemented with multicomponent interventions. These included small group educational sessions led by opinion leaders, an electronic version of the guideline, audit with feedback, and enhanced clinical orders support. Medical records of random samples of patients with diabetes were audited for specific diabetes performance measures on a monthly basis. Baseline data were compared with results at the end of the implementation effort. SETTING: Southeastern Minnesota, excluding Olmsted County. PARTICIPANTS: Adult patients seen at one practice of 18 general internists. OUTCOME MEASURES: Outcome measures included Hb A1c values and annual performance of a urine protein test, foot examination, and dilated eye examination. RESULTS: Gradual, sustained; and statistically significant improvements in the three annual performance measures were observed. Urine protein testing increased from 24% to 66% (P = 0.001), dilated eye examinations increased from 63% to 84% (P = 0.001), and foot examinations increased from 86% to 97% (P = 0.001). Mean Hb A1c values +/- SD also improved from 7.8% +/- 1.0% to 7.1% +/- 0.7% (P < 0.001) in patients who received continuing care for diabetes. CONCLUSIONS: Statistically significant improvements were observed after continuous improvement efforts were focused on providers in an individual group practice. When used to implement a diabetes guideline, such interventions may improve delivery of services and reduce Hb A1c levels in patients with diabetes.

Adult↗