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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

10 recordsLinked to original sources

In vitro activity of cefamandole, cefoxitin, cefuroxime, and carbenicillin, alone and in combination with aminoglycosides against Serratia marcescens.

Synergistic antibiotic studies were undertaken to compare the effectiveness of two new beta-lactamase resistant cephalosporins, cefamandole, and carbenicillin, with four aminoglycosides against clinical strains of Serratia marcescens. The strains demonstrated various combinations of resistance and/or susceptibility to the antibiotics tested. Tobramycin was the most effective aminoglycoside when used in combination with beta-lactam antibiotics. Carbenicillin and cefamandole demonstrated similar activity with aminoglycosides in synergy experiments. Tobramycin-carbenicillin was found to be the superior pairs as indicated by the total number of strains inhibited. This combination was the only one effective against certain high drug resistant strains and the strain resistant to all four aminoglycosides. Carbenicillin or cefamandole with tobramycin exhibited comparable activity against multiple drug resistant organisms. However, mutants significantly more resistant to cefamandole developed during susceptibility testing. The findings of this study have clinical relevance for treating infections by this formidable pathogen.

Amikacin

Role of cytochrome P-450 in alveolar hypoxic pulmonary vasoconstriction in dogs.

Alveolar hypoxia induces pulmonary vasoconstriction by an unknown mechanism. Cytochrome P-450 (C-P450) is found in the lung and may modify pulmonary vascular tone via its sensitivity to changes in oxygen tension or by affecting metabolism of a chemical mediator. Metyrapone and carbon monoxide are both inhibitors of C-P450. We tested alveolar hypoxic pulmonary vasoconstriction (AHPV) in 20 dogs before, during, and after separate administration of each inhibitor. Anesthetized dogs were ventilated through a double lumen endotracheal tube allowing ventilation of one lung with N(2) or CO as a hypoxic challenge and ventilation of the other lung with O(2) to maintain adequate systemic oxygenation. Distribution of lung perfusion was determined with intravenous (133)Xenon and external chest detectors. Before infusion of metyrapone, mean perfusion to the test lung decreased 30% with alveolar hypoxic challenge, but decreased only 10% during metyrapone infusion and returned to a base-line mean decrease of 31% after completion of metyrapone infusion. Prostaglandin F(2) alpha and angiotensin II infusions produced equivalent increases in pulmonary vascular resistance before and during metyrapone infusion. Before CO, mean test lung perfusion decreased 31% with alveolar hypoxia but was reduced only 10% from control when unilateral end-tidal CO% was >75%. Washout of alveolar CO with unilateral N(2) ventilation restored AHPV, with perfusion decreasing 29% from control. Thus, both metyrapone and carbon monoxide can reversibly inhibit AHPV. C-P450 may, therefore, be involved in the transduction process of the vasoconstrictor response to alveolar hypoxia.

Angiotensin II

Multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type, with restrictive and obstructive lung disease.

Multiple peripheral carcinoid tumors were found on lung biopsy in a 53 year old woman with an eight year history of pulmonary nodules. The biopsy specimen showed nodules varying from 1 to 7 mm in greatest diameter. The larger lesions were typical bronchial carcinoids whereas the smaller ones resembled pulmonary "tumorlets." Electron microscopy showed neurosecretory granules typical of carcinoids. The common multicentric origin of carcinoids and tumorlets from Kulchitsky cells is discussed. Pulmonary function testing revealed mild obstructive and restrictive defects, both attributed to the carcinoid tumors. The history, pathology and physiology of this unusual case are presented in detail, with a review of the literature. Obstructive airways disease, presumably due to the extensive bronchiolar involvement, has not previously been reported in this entity.

Airway Obstruction

Factors which influence blood platelet migration.

Migration of human blood platelets in vitro was investigated by a modification of the capillary-tube migration chamber technique used to study the migration inhibition factor of macrophages. Platelets were packed in capillary tubes and incubated in autologous platelet-free plasma (PFP). The extent of migration was quantified by planimetry (measurement of the area of platelet migration visible by stereomicroscopy). Among the various anticoagulants employed, sodium citrate was most suitable for studying platelet migration. Optimal migration occured at 22 degrees to 37 degrees C and pH 7.2 to 7.4. Migration was inhibited by metabolic inhibitors such as iodoacetic acid, sodium fluoride, and 2,4-dinitrophenol, and inhibition was proportional to the dose of the agent added to the incubation medium. Mobility was also inhibited by cytochalasin B, which disrupts cellular microfilaments, at 1 microgram/ml PFP, but not by colchicine, a microtubule inhibitor, even at 40 microgram/ml of PFP. Light and electron microscopy showed that this inhibition was not ascribable to platelet clumping. These observations suggest that platelet mobility is an active process. The possible significance of platelet migration in hemostasis is discussed.

Anticoagulants

California encephalitis virus development in mosquitoes as revealed by transmission studies, immunoperoxidase staining, and electron microscopy.

Isolates of the snowshoe hare subtype of California encephalitis (CE) virus from Yukon mosquitoes during 1972 and 1973 were transmitted by bites of Aedes aegypti mosquitoes after 4 to 5 weeks of extrinsic incubation at 55 degrees F after intrathoracic injection, and the 1973 strain was transmitted after mosquitoes were fed virus and held for 3 to 4 weeks at 75 degrees F. Antigen of a 1971 isolate of CE virus (Marsh Lake 23) was detected in salivary glands of infected mosquitoes by the immunoperoxidase technique, using highly purified antiserum before and after conjugation with horseradish peroxidase, plus the use of orthotolidine as a substitute for benzidine. enveloped virions 45 nm in diameter were observed in thin sections of salivary glands of Culiseta inornata mosquitoes 59 days after intrathoracic injection with the 1971 isolate, afterincubation at 55 degrees F.

Aedes

California encephalitis virus prevalence throughout the Yukon Territory, 1971-1974.

California encephalitis (CE) virus (snowshoe hare subtype) was isolated from 1 of 38 pools comprising 970 unengorged female Aedes canadensis mosquitoes and from 3 of 152 pools containing 5,676 A. communis mosquitoes which were collected in the Yukon Territory, Canada between latitudes 61 and 66 degrees N during June and July 1974. During four summers 1971 through 1974, this virus was recovered from 26 of 648 pools derived from 30,686 mosquitoes of 4 species. Isolation of CE virus from 1 of 109 pools of Aedes sp. larvae collected during May 1974 suggests maintenance of this virus over winter by transovarial transfer. Infectivity has been maintained in Culiseta inornata mosquitoes which were held continuously at 32 degrees F for 138 days. Neutralizing antibodies to CE virus were detected in 705 of 4,913 (14%) mammals collected during summers 1971 through 1974, including 430 of 1,076 (40%) snowshoe hares (Lepus americanus), 266 of 3,610 (7%) ground squirrels (Citellus undulatus) and 9 of 227 (4%) red squirrels (Tamiasciurus hudsonicus).

Aedes