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Biomedical subjects

J F Murray

Publications and source records attributed to J F Murray.

At least 163 records · Page 9Linked to original sources
PubMed1977

Acedapsone treatment of leprosy patients: response versus drug disposition.

In 22 lepromatous Filipino patients receiving their first injection of 225 mg acedapsone (DADDS), dapsone (DDS), and monoacetyl DDS (MADDS) were present in plasma in approximately equal quantities. Peak levels of parent drug, DDS, and MADDS occurred between 22 and 35 days. The half-times of disappearance (T1/2) from plasma were 43 days for DDS and MADDS and 46 days for DADDS. Acetylator phenotyping with sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators. Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and DADDS were highly significant. However, acetylation of DDS after DADDS did not differentiate the patients into acetylator phenotypes. The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after DADDS treatment. These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily. No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients. In a companion study, minimum levels of DADDS, MADDS, and DDS were determined in 447 leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg DADDS every 70 to 80 days for the past 5 years. All patients exhibited DDS levels above the MIC of DDS for M. leprae, no significant differences in plasma sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and sulfone levels were found, and type of response in multibacillary patients and sulfone levels were unrelated. No substantial accumulation of the sulfones in the Karimui patients receiving continuous therapy with DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of DADDS.

Acedapsone↗
PubMed1976

Effects of continuous positive-pressure ventilation in experimental pulmonary edema.

We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.

Animals↗
PubMed1975

Chromatographic-fluorometric analysis of antileprotic sulfones.

Modifications to the power supply system of a spectrophotofluorometer are described. These modifications stabilize the output of the xenon are lamp and permit the determination of nanogram quantities of antileprotic sulfones. The sulfones are removed from plasma by a single extraction with ethyl acetate, then separated by high-pressure liquid chromatography on silica, and detected in the effluent by their fluorescence. The method is specific, rapid, and reproducible.

Autoanalysis↗
PubMed1975

Minimal inhibitory concentration of dapsone for Mycobacterium leprae in rats.

To define the minimal inhibitory concentration (MIC) of dapsone (DDS) for Mycobacterium leprae in rats, we determined the relationship between dietary and plasma levels of DDS in uninfected male and female Lewis rats. This knowledge was applied to the design of experiments using rats inoculated in the footpads with M. leprae. The MIC for DDS in male and female rats, respectively, was 1.5 to 4.0 ng and 1.8 to 3.0 ng of DDS/ml of plasma, even though the sexes exhibited markedly different concentrations of DDS when receiving the same dietary level of DDS. These values for the MIC of DDS for M. leprae in rats are nearly identical to the previously determined MIC of DDS for M. leprae in mice.

Animals↗
PubMed1975

Effect of norepinephrine and fluid administration on pulmonary extravascular water volume in dogs.

The effects of norepinephrine-induced vasoconstriction on pulmonary extravascular water volume (PEWV) and central volume were studied before and after intravenous volume expansion with 5% dextrose and water (20 ml/kg body weight). PEWV was measured by double isotope dilution and gravimetric analysis and assessed by electron photomicrography. Comparisons were made with saline-treated control dogs. Thirty-six dogs were studied after they had been anesthetized with sodium pentobarbital. PEWV determined by indicator dilution increased during norepinephrine infusion, especially after volume expansion; in contrast, PEWV in control dogs was constant despite similar increases in pulmonary arterial and left atrial pressures. However, measurements of PEWV by gravimetric analysis and inspection of electron photomicrographs failed to reveal extravascular accumulation of water in vasoconstricted dogs. Thus, it was concluded that the increased PEWV measured by indicator dilution in norepinephrine-treated dogs compared with that in saline-treated dogs reflects more complete perfusion of pulmonary capillaries and access of the diffusible indicator to additional lung tissues and spaces. Improved capillary filling presumably is attributable to peripheral vasoconstriction and redistribution of blood into the thorax. PEWV determined by gravimetric analysis in dogs that had had open-chest procedures for lung biopsy and electron photomicrography was significantly less than that in dogs with their chests closed throughout the experiments. Although the mechanism for the water loss in unknown, the difference must be recognized when the results from various types of experiments are compared.

Animals↗
PubMed1975

Disposition of dapsone and monoacetyldapsone in rats.

Female Buffalo and Lewis rats receiving 1.0 mg DDS/kg ip exhibited higher plasma levels of DDS and its monoacetylated metabolite, MADDS, than did male rats of each strain receiving the same dose. The fraction of the total measured drug in plasma as MADDS at 8 hr in female rats of both strains ranged from 43 to 62% compared with a range of 28-31% in male rats. Plasma half times of disappearance (T1/2) of DDS ranged from 5.0 to 6.8 hr and were not different among sexes and strains. Deacetylation of MADDS to DDS occurred when equimolar doses of MADDS were administered. An approach to a steady state of acetylation-deacetylation was indicated by comparing the percentage MADDS of the total drug in plasma in the respective sexes and strains receiving both drugs. T1/2 values of MADDS were significantly lower than values for DDS in Lewis rats. They were not different in Buffalo rats. Protein binding studies in plasma from rats receiving 5.0 mg DDS or 5.8 mg MADDS/kg showed 67-72% binding of DDS and 91% binding of MADDS. These in vivo observations were confirmed by in vitro binding studies. Comparison of these results with those of earlier studies in mice and man indicates that the rat is a better model of man than is the mouse for studies on the disposition of DDS.

Animals↗
PubMed1975

Fractures of the mandible in motor vehicle accidents.

Motor vehicle accidents are a common cause of fractures of the mandible and are the most common cause of serious and multiple fractures. The usual mechanism of injury is outlined. The common fractures that occur are through the anterior alveolar process, condylar necks, or edentulous areas of the body and symphysis. There is high incidence of other injuries associated with jaw fractures in these patients. Treatment of the mandibular fracture must wait until the patient's general condition is stabilized. Obstruction of the airway demands emergency treatment by keeping the tongue forward and repeated suction of blood and mucus from the mouth and nasopharynx. Emergency tracheostomy is rarely necessary because of mandibular fractures. The methods for immobilizing a fractured jaw are outlined. The majority of accident victims are young and therefore have teeth. When there are teeth that occlude immobilization of the mandible must include intermaxillary fixation by wiring the teeth into occlusion. Interosseus wiring is used to support unstable fragments. Intramedullary Kirschner wires are a simple and effective method for immobilizing fractures through the body and symphysis of edentulous patients.

Accidents, Traffic↗