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Biomedical subjects

T M Marshall

Publications and source records attributed to T M Marshall.

14 recordsLinked to original sources

Use of intra-aortic nitroglycerin in the cardiac catheterization laboratory.

The purpose of this study was to determine whether nitroglycerin (NTG) injected into the ascending aorta or left ventricle would safely and effectively lower blood pressure in hypertensive patients undergoing cardiac catheterization. Fifty bolus injections of 297 +/- 67 micrograms (mean +/- SD) NTG were given to patients with a systolic blood pressure (SBP) of > or = 140 mm Hg (mean SBP 188 +/- 20.1 mm Hg). An average drop in systolic blood pressure of 36 +/- 16 mmHg (P < 0.001), diastolic blood pressure of 19 +/- 7 mm Hg (P < 0.001), and left ventricular end-diastolic pressure of 4.7 +/- 4 mm Hg (P = 0.001) was well tolerated in each patient. The mean time to response was 11 +/- 3 sec. Intra-aortic injection of NTG is a safe and effective means to treat hypertensive patients in the cardiac catheterization laboratory.

Adult↗

Successful treatment of deglutition syncope with oral beta-adrenergic blockade.

A case of deglutition syncope of 20 years' duration in a patient without cardiac or esophageal disease is presented. The therapeutic efficacy of beta-blockade is documented by symptomatic improvement, repeat esophageal balloon inflation and tilt-table testing. This suggests the Bezold-Jarisch reflex or sympathetic nervous system may be involved in the pathogenesis of deglutition syncope.

Administration, Oral↗

Radiobiological studies with the nematode Caenorhabditis elegans. Genetic and developmental effects of high LET radiation.

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space.

Animals↗

Atrial paralysis in a patient with Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss disease is a benign X-linked muscular dystrophy characterized by a distinct pattern of muscle weakness, which is of insidious onset and slow progression. It is associated with atrial paralysis that results in sudden death in early adulthood if left untreated. The authors report the documentation of electrical and mechanical silence confined to the atria in a patient with this disease. Electrocardiography and electrophysiological study document the absence of electrical atrial activity, and inability to pace the atria. Hemodynamic studies demonstrate the absence of A waves, and angiography revealed immobility of the atria. This patient has done well following the institution of permanent ventricular pacing. His brother, who also had muscular dystrophy, died a sudden cardiac death at the age of 29 after refusing medical intervention. Emery-Dreifuss muscular dystrophy is particularly worthy of recognition because of the preventable occurrence of sudden death in young patients with an otherwise excellent prognosis. Permanent ventricular pacing is indicated.

Adult↗

Hydrogen peroxide increases the availability of arachidonic acid for oxidative metabolism by inhibiting acylation into phospholipids in the alveolar macrophage.

Reactive oxygen species stimulate metabolism of arachidonic acid (AA) to eicosanoids in a variety of cells and tissues, yet the pathway(s) by which oxidants increase the availability of AA for oxidative metabolism are not known. Thus, we explored the effects of hydrogen peroxide (H2O2) on deacylation and reacylation of AA to determine the enzymatic mechanism(s) by which this oxidant increases levels of free, unesterified AA, and thereby its oxidative metabolism to eicosanoids, in the rat alveolar macrophage (AM). Over the range from 0.1 to 0.5 mM, H2O2 caused marked time- and dose-dependent inhibition of incorporation of [3H]AA into macrophage phospholipids, whereas calcium ionophore A23187 and zymosan particles did not cause such inhibition. Within this concentration range, there was an almost exact reciprocal correlation between inhibition of [3H]AA acylation and H2O2-stimulated accumulation of free [3H]AA in prelabeled AM cultures. Thimerosal, which blocks AA reacylation but spares deacylation via phospholipase A2 (PLA2), did not affect accumulation of free [3H]AA in prelabeled cells stimulated with H2O2, while markedly augmenting [3H]AA release in response to A23187 and to zymosan. Despite its ability to block AA acylation almost completely, H2O2 did not directly inhibit arachidonoyl CoA synthetase or arachidonoyl CoA:lysophosphatide acyltransferase, which catalyze AA incorporation into phospholipids. However, H2O2 (0.1 to 0.5 mM) markedly depleted AMs of ATP, required for synthesis of the acylation intermediate arachidonoyl CoA, suggesting that this was the means by which H2O2 inhibited acylation. Notably, H2O2 (0.03 to 3 mM) failed to stimulate macrophage PLA2 activity. We conclude that H2O2, in contrast to A23187 and zymosan, inhibits incorporation of AA into phospholipids, and that this represents the major mechanism by which the oxidant increases the availability of free AA for oxidative metabolism in the AM. This may be an important basis for release of eicosanoids in oxidant-induced inflammation and injury of the lung.

Acylation↗

Reversible tricuspid regurgitation in a patient undergoing treatment for acute leukemia.

A 52-year-old female patient treated for acute lymphoblastic leukemia with combination chemotherapy (cyclophosphamide, vincristine, adriamycin and prednisone), broad spectrum antibiotics and amphotericin via a Hickman catheter placed in the superior vena cava, developed echocardiographically confirmed tricuspid regurgitation. A second admission four months later showed only mild tricuspid regurgitation. The authors conclude that the amphotericin given via the central line caused valvulitis of the tricuspid valve.

Amphotericin B↗

Differential dependence on protein kinase C of arachidonic acid metabolism stimulated by hydrogen peroxide and by zymosan in the alveolar macrophage.

The dependence on protein kinase C (PKC) of arachidonic acid (AA) metabolism stimulated by the biologically important oxidant H2O2, as compared to zymosan particles, was investigated in the rat alveolar macrophage. The PKC inhibitor staurosporine markedly reduced AA release and eicosanoid synthesis stimulated by zymosan, but only slightly inhibited AA release and metabolism induced by H2O2. Furthermore, in macrophages depleted of PKC by extended exposure to phorbol 12-myristate 13-acetate, AA release in response to zymosan was greatly inhibited, whereas that stimulated by H2O2 was attenuated to a significantly lesser degree. Thus, zymosan-stimulated AA metabolism requires active PKC, whereas H2O2-induced metabolism is largely PKC-independent. This provides direct evidence for the existence of two pathways of agonist-stimulated AA metabolism, which differ in their dependence on PKC, in the alveolar macrophage.

Alkaloids↗

Radiation effects in Caenorhabditis elegans, mutagenesis by high and low LET ionizing radiation.

The nematode C. elegans was used to measure the effectiveness of high-energy ionized particles in the induction of 3 types of genetic lesions. Recessive lethal mutations in a 40-map unit autosomal region, sterility, and X-chromosome nondisjunction or damage were investigated. Induction rates were measured as a function of linear energy transfer, LET infinity, for 9 ions of atomic number 1-57 accelerated at the BEVALAC accelerator. Linear kinetics were observed for all 3 types of lesions within the dose/fluence ranges tested and varied strongly as a function of particle LET infinity. Relative Biological Effectiveness (RBE) values of up to 4.2 were measured and action cross sections were calculated and compared to mutagenic responses in other systems.

Animals↗

Medical liability.

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Insurance, Liability↗