Biomedical subjects
Publications and source records attributed to T M Brown.
This article reviews the current data available on the most frequently used drugs in bronchopulmonary dysplasia. Oxygen, diuretics, bronchodilators, steroids, ribavirin, and antioxidants, as well as medication available for pulmonary hypertension, systemic hypertension, and gastroesophageal reflux are discussed, with emphasis on known advantages, side effects, and current dosage.
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Concentrations of [carboxyl-14C]procaine in blood of mice were increased threefold for 27 min by exposure to O-4-nitrophenyl diphenylphosphinate 2 hr prior to [carboxyl-14C]procaine injection ip, while there was no effect of O-4-nitrophenyl methyl(phenyl)phosphinate pretreatment. There was no effect of either organophosphinate on the primary hydrolysis of [acetyl-l-14C]aspirin when assessed by the expiration of [14C]carbon dioxide; however, O-4-nitrophenyl diphenylphosphinate pretreatment produced transient increases in blood concentrations of both [carboxyl-14C]aspirin and [carboxyl-14C]salicylic acid following administration of [carboxyl-14C]aspirin. Liver carboxylesterase activity in O-4-nitrophenyl diphenylphosphinate pretreated mice was 11% of control activity. These results indicate the potential for drug interaction with O-4-nitrophenyl diphenylphosphinate but not with O-4-nitrophenyl methyl(phenyl)phosphinate. It appears that liver carboxylesterase activity has a minor role in hydrolysis of aspirin in vivo, but may be more important in procaine metabolism.
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Porcine liver carboxylester hydrolase (EC 3.1.1.1; carboxylesterase) was rapidly inhibited by 4-nitrophenyl organophosphinates containing aryl or heteroaryl groups directly bound to phosphorus. The most potent inhibitor was 4-nitrophenyl di-2-thienylphosphinate for which the median inhibitory concentration was 7.4 X 10(-9) M. Rabbit liver monomeric carboxylester hydrolase was inhibited, separated from excess inhibitor by gel permeation chromatography, and observed for spontaneous or 1,1'-trimethylene-bis(4-formylpyridinium bromide) dioxime (TMB-4)-induced reactivation. Recovery was most rapid (k = 4 to 7 X 10(-4) min-1) from phosphinyl groups containing one alkyl substituent smaller than isopropyl and one aryl or heteroaryl group smaller than naphthyl. The di-2-thienylphosphinylated enzyme was an exception since it recovered rapidly while lacking an alkyl substituent. Oxime reactivation by TMB-4 doubled rates of recovery.
Without a cell wall, the morphology, growth rate, and composition of mycoplasmas are culture media-dependent with variable properties best described as environmentally related. The adaptation of mycoplasmas to either a tissue cell or cell-free culture media, with dependency upon specific animal or plant products for survival, has led to investigations of their human host-related properties. The influence of culture media on the antibiotic sensitivities of mycoplasmas was measured by use of three different broths in two different assay systems. The variable results indicate that the inhibition of mycoplasma protein synthesis or growth may also be host-tissue dependent. The addition of noninhibitory penicillins to different culture media was found to affect the composition and antigenicity of some mycoplasmas. Using the complement fixation test, we found some human sera that were more reactive than rabbit antisera to mycoplasmas cultured in human synovial broth or in myelin-enriched broth. Mycoplasmas cultured in human lung broth and pig lung broth had media-dependent antigenicity. The antigenicity and the growth of mycoplasmas were found to depend on the proteolytic enzymes used to provide the essential peptides in tissue broths. The media-affected mycoplasmas indicate the presence of species-, strain-, and tissue-specific antigen sites that may determine immunopathogenicity in the genetically susceptible host.
Examination of recently isolated cultures of three strains of Contagious Equine Metritis Organism grown on specially formulated, serum-free, clear typing medium revealed the presence of numerous colonial opacity variants. These colonies were prepared by a number of fixation and staining techniques and examined by scanning and transmission electron microscopy. Opaque and transparent phenotypes produced copious amounts of extracellular material compared with intermediate-opacity phenotypes which produced little or none. Also unique to intermediate colonies were numerous thin intercellular strands, which may represent pili or polymers of extracellular material. The presence of an unusual fibrillar layer (with similar electron density to the extracellular material) on the outer leaf of the outer membrane also was confirmed. A number of other ultrastructural features also were noted, including an epilayer, a thin nonmembranous layer which covered colonies and adjacent agar.
Seven male patients with cyanotic congenital heart disease were studied. Serum testosterone, androstenedione, dehydroepiandrosterone, thyroxine and triiodothyronine levels did not differ significantly from control values. Thyroid stimulating hormone and prolactin responses to injected thyrotrophin releasing hormone were normal. Impaired gonadotrophin responses to injected gonadotrophin releasing hormone were noted in two patients. The hypothalmic-pituitary-testicular axis appears to be better preserved in cyanotic congenital heart disease than in chronic obstructive airways disease and restrictive lung disease for a similar degree of hypoxia. Possible explanations are discussed.
Eight men with hypoxia associated with idiopathic pulmonary fibrosis were studied. Serum testosterone concentrations were low in two subjects and fell to subnormal levels in two others as the clinical condition and arterial oxygen tension deteriorated. There was a significant correlation between serum testosterone concentrations and arterial oxygen tensions (p less than 0.05). Three patients showed evidence of suppression of luteinising hormone secretion at the pituitary level. Only occasional abnormalities of thyroid and prolactin concentrations were noted. Most of the men suffered from organic sexual impotence, which is considered to be due at least in part to endocrine disturbance. These findings are similar to observations in patients with hypoxic chronic obstructive airways disease and support the hypothesis that hypoxia of lung disease suppresses the hypothalamo-pituitary-testicular axis.
The morphological heterogeneity of lipopolysaccharides (LPSs) among salmonella mutants with different LPS chemotypes was analyzed in silver-stained polyacrylamide gels. The biochemical differences in the LPS chemotypes were reflected in the unique profiles of the purified LPSs. The LPS profiles in the whole-cell lysates were also unique for each chemotype. (Whole-cell lysates were assessed by a method which preferentially silver stains LPS and by a proteinase K digest of whole-cell lysates. The silver-stained LPS profiles of proteinase K-digested lysates were similar to the homologous purified LPS and could be used to preliminarily characterize the LPS chemotype before purification.) In summary, biochemical variation in LPS composition can be detected in silver-stained polyacrylamide gels.
We present an unusual case of extreme metabolic alkalosis resulting from severe hypokalaemia caused by unmonitored fludrocortisone therapy. Biochemical aspects of the disorder are discussed, as is the successful treatment with diuretics and potassium replacement. Some dangers of this therapy and necessary precautions are emphasized.
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A patient with acute right ventricular failure and severe hemodynamic instability following coronary artery revascularization was treated with intra-aortic and intravenous balloon pumping. The intravenous balloon was timed to inflate during diastole and deflate during systole as did the intra-aortic balloon; in fact, the two were connected to the same system through a Y-connector. The intravenous balloon acted as an artificial atrium, which allowed approximately 20% improvement in the cardiac output when this intravenous balloon was functioning. Hemodynamic stability was achieved with this system. Intravenous balloon pumping should be considered for patients with unstable hemodynamics secondary to acute right ventricular failure.
Polymorphonuclear leukocytes (PMN) chemotaxis and serum chemoattractant ability were studied in patients with rheumatoid arthritis (RA) employing the agarose plate technique. No statistically significant differences were observed in random migration of unstimulated cells compared to the controls. Moreover, there were no statistically significant differences between the chemotactic migration of control and patient cells in response to a number of non-treated sera. The chemotactic responsiveness of normal PMN cells to treated rheumatoid serum was significantly less than that observed using treated control serum with Escherichia coli lipopolysaccharide. The possible explanation for this abnormality may be due to the presence of chemotactic inhibitors in some RA serum. No correlation was detected between chemoattractant activity of rheumatoid arthritis serum, circulating immune complexes or rheumatoid factor. There were no statistically significant differences in the adhesiveness of RA-PMNs compared to normal PMNs.
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One hundred fifty-six patients underwent emergency coronary revascularization during the early phases of evolving myocardial infarction (MI). There were six hospital deaths (3.8%) and two later deaths (1.3%). Thrombectomy of the MI artery was achieved in 79% of the patients, and 17% of the patients showed no observable lesion in the MI vessel on restudy. Graft patency was 99%. Late follow-up to 62 months disclosed 17 patients with residual limitations. Analysis of the data established criteria for recognizing patients with early MI who would benefit from surgical therapy. The criteria are derived by comparing preoperative and postoperative ventricular anatomy, creatine phosphokinase levels, and hemodynamics.
Coronary artery spasm is a well-documented phenomenon in patients undergoing medial treatment. We describe coronary artery spasm occurring in the immediate postoperative period following coronary artery bypass operation. The spasm occurred in a vessel that was not operated on and that had no apparent lesion. The diagnosis of spasm was made by coronary angiography immediately after operation. Complications associated with this spasm are discussed. Emphasis is placed on early postoperative angiography for patients whose condition is inexplicably unstable after operation.