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Biomedical subjects

T Murray

Publications and source records attributed to T Murray.

At least 91 records · Page 5Linked to original sources
PubMed1983

An internally-standardized assay for amphotericin B in tissues and plasma.

A high-performance liquid chromatographic (HPLC) method with p-nitrophenol as internal standard is described for the rapid analysis of amphotericin B recovered by methanolic extraction from tissues and plasma. Programmed, gradient elution of the ODS column was used with detection by tungsten light at 388 nm. Standard curves were derived based on the peak height ratios. The lowest reproducible limit of the assay was 0.04 micrograms/ml with plasma. The extraction and chromatographic procedures recovered 53-71% of the amphotericin B from each of these sources. The coefficient of variation of the recovery ratios was less than 18% from plasma over a range of concentrations of amphotericin B from 0.08 to 10.0 micrograms/ml. Recovery from tissues, studied over a narrower concentration range, showed a similar degree of precision. Variations in precolumns apparently resulting in selective binding of the amphotericin B were found to have a systematic but important influence on recovery efficiency. No substances were detected which interfered with the assay procedures as described. By incorporating an internal standard we have enhanced the reliability and flexibility of the HPLC assay for amphotericin B especially for assay of tissues.

Amphotericin B↗
PubMed1983

Drug convertarule.

A convenient pocket ruler has been developed that allows conversion between metric and molar measurements of many of the drugs for which therapeutic monitoring in the circulation is commonly used. The ruler also gives information to the clinician on suggested therapeutic ranges for the incorporated drugs.

Metric System↗
PubMed1983

Categorization in accident departments: 'good' patients, 'bad' patients and 'children'.

Children form a significant proportion of accident services' clientele but have received relatively little attention in the growing ethnographic literature on such organizations. This paper uses data from observation and interviews in four English accident departments to review Jeffery's influential analysis of medical staff's categorization of patients. After pointing to certain logical difficulties with this account, it is argued that an analysis of the way children are treated allows for these to be remedied by the development of a more sophisticated model of professional decision-making. The paper concludes with a discussion of the way in which the categorization rests on the practical contingencies of accident work and the social organization of emergency work. Attention is drawn to the variation between high-prestige units in teaching hospitals and lower-status units in general hospitals and the way this limits the ability of the former to identify conditions like child abuse or neglect.

Attitude of Health Personnel↗
PubMed1982

Degradation of isolated deoxyribonucleic acid mediated by nitroso-chloramphenicol. Possible role in chloramphenicol-induced aplastic anemia.

Reduction of the nitro group of chloramphenicol (CAP) gives rise to more highly reactive intermediates which may in involved in the aplastic anemia associated with CAP use. One such intermediate, nitroso-chloramphenicol (NO-CAP), has been found to be a potent agent for mediating degradation of isolated DNA. In a reaction mixture containing 100 microM NO-CAP, 100 microM CuCl2, and 5 mM NADH, 7 micrograms of Escherichia coli [3H]DNA was completely degraded to acid-soluble fragments in 30 min. Damage to DNA was in the form of single-stranded scissions. The requirement for copper was specific, and copper chelating reagents blocked the degradation. The need for a reducing agent could be met equally well by NADH or NADPH, but not by sulfhydryl reagents such as glutathione, dithiothreitol and 2-mercaptoethanol. Oxygen was also necessary for the NO-CAP mediated DNA damage, with reduced forms of oxygen participating in the reaction. A role for H2O2 was indicated by the inhibition of the degradation seen when catalase was included in the mixture. Hydroxyl radicals are known to be produced in the reaction of H2O2 with certain transition metals. Scavangers of hydroxyl radicals also inhibited strand-scission, suggesting that the radicals may be the primary agents in DNA degradation. The importance of the nitroso moiety of NO-CAP was evidenced by the lack of DNA damage seen when NO-CAP was replaced by CAP under the conditions tested.

Anemia, Aplastic↗
PubMed1981

The nitroreduction of chloramphenicol by human liver tissue.

Fresh-frozen human liver tissue was assayed for its ability to reduce the nitrogroup of R--NO2 to the amine. All 10 livers examined exhibited demonstrable reductase activity. The reduction was potentiated by NADPH and abolished by boiling the liver homogenates. The nitroreductase activity varied among the different livers by as much as severalfold. These findings show that ability of the human liver to reduce R--NO2 and support the hypothesis that certain toxic intermediates of the nitroreduction of R--NO2 may be responsible for the aplastic anemia associated with this drug.

Chloramphenicol↗
PubMed1981

The cellular uptake and covalent binding of nitroso-chloramphenicol.

A comparative study of the cellular transport of CAP and its nitroso derivative (NO-CAP) was carried out in Raji cells, a transformed human lymphoblastoid cell line. Both agents were concentrated by the cells by a factor of 3 (cellular/extracellular concentration ratio). The cellular uptake of NO-CAP, like that of CAP, was found to be rapid and temperature-independent. Thus the greater cytotoxicity of NO-CAP is apparently not due to an enhanced uptake of the nitroso derivative relative to CAP. In contrast to the similarity of uptake, NO-CAP becomes covalently bound to both Raji cells and freshly isolated human bone marrow cells to a much higher extent (15-fold). Also, cells previously loaded with CAP or NO-CAP retain three times as much of the nitroso compound during a 24 hr dialysis against a drug-free isotonic solution. The increased binding of NO-CAP to human hematopoietic cells attests to the greater reactivity of the p-substituted aromatic nitroso group and is consistent with the postulate that reduction products of the nitro group of CAP may be responsible for CAP-induced aplastic anemia.

Anemia, Aplastic↗
PubMed1980

Inhibition of adipose conversion in 3T3-L2 cells by retinoic acid.

The role of retinoic acid in modulating the differentiation of 3T3-L2 fibroblasts into adipocytes has been examined. Results indicate that the retinoid is capable of effectively inhibiting the degree of adipose conversion which is brought about by treatment of preadipocytes with 1-methyl-3-isobutylxanthine plus dexamethasone. MOrphological and enzymatic (fatty acid synthetase activity) expression of the adipose phenotype are both inhibited more than 90% by 10(-6) M retinoic acid. The inhibition is concentration dependent with retinoic acid must be administered simultaneously with the triggering agents to be effective. Exposure of nongrowing preadipocytes to retinoic acid does not alter the ability o the cells to differentiate in response to a subsequent treatment with methylisobutylxanthine plus dexamethasone. Further, the inhibition is reversible. Cultures i which methylisobutylxanthine plus dexamethasone triggered differentiation has been blocked by addition of retinoic acid (10(-6) M) will readily undergo adipose conversion in response to a second treatment with methylisobutylxanthine plus dexamethasone in the absence of the retinoid. Similar inhibition of differentiation was found when cultures were treated with drugs in medium supplemented with either newborn calf serum or fetal calf serum. However, the extent to which methylisobutylxanthine plus dexamethasone are able to promote differentiation in these cells is considerably greater in medium containing fetal calf serum.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Uptake of gentamicin by separated, viable renal tubules from rabbits.

The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.

Aminoglycosides↗
PubMed1980

Acquisition of an insulin-sensitive activity of adenosine-3',5'-monophosphate phosphodiesterase during adipose conversion of 3T3-L2 cells.

Mouse 3T3-L2 fibroblasts differentiate when cultured and express a new phenotype which is characteristic of adipose cells. One aspect of this differentiation is the acquisition of hormone sensitivities typical of adipocytes. The sensitivity of adenosine-3',5'-monophosphate (cAMP) phosphodiesterase to brief insulin treatment in 3T3-L2 cells at various stages of adipose conversion was examined. The capacity to increase the activity of a low-Km form of the enzyme in response to acute insulin exposure is a property which is acquired as the cells begin to express the adipose phenotype. Enzyme activity in preadipocytes is not affected by inslin, nor is there an effect in the non-differentiating 3T3-C2 line under any of the conditions tested. Since insulin receptors and cAMP phosphodiesterase are both present in the preadipocytes, one result of this cytodifferentiation is to effectively couple receptors to the enzyme activity. Insulin-sensitive cAMP phosphodiesterase in 3T3-L2 adipocytes is characterized by a 40-50% increase in enzyme activity during insulin treatment when determined at 0.1 microM cAMP. This activation results from an increase in the apparent V of the enzyme and does not involve a change in enzyme-substrate affinity. Maximal stimulation is seen within 2-5 min and is sustained for at least 45 min when high levels of insulin (850 nM) are used. Lower concentrations of insulin (1.7 nM) also bring about rapid activation, although the activation is not completely sustained during longer incubations. Stimulated activity falls off to about 60% of peak values by 30 min. Re-addition of insulin after 30 min raises enzyme activity back to the maximal level. Further, the insulin response is completely reversible in that the insulin-sensitive cAMP phosphodiesterase activity disappears within 10 min after removal of insulin from the cultures.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Cyclic adenosine-3',5'-monophosphate stimulates islet B cell replication in neonatal rat pancreatic monolayer cultures.

A possible role for cyclic adenosine 3',5'-monophosphate (cAMP) in islet B cell replication was examined in neonatal rat pancreatic monolayer cultures. Islet cells deteriorated and insulin release decreased during 12 d of culture in medium with 5.6 mM glucose, whereas the cells survived and insulin release increased during culture in medium with 5.6 mM glucose plus the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM), or in medium with 16.7 mM glucose with or without IBMX. IBMX also increased the mitotic index and stimulated dose-dependent increases in [(3)H]thymidine incorporation in nuclei of islet B cells in aldehydethionine stained radioautographs; maximal stimulation of B cell replication occurred with addition of 0.1 mM IBMX to 5.6 mM glucose (+170%, P < 0.001), and this increase was similar to that observed with 16.7 mM glucose (+185%, P < 0.001). Also, 8-bromo-adenosine-3',5-monophosphate, but not 8-bromo-guanosine-3',5'-monophosphate produced dose-dependent increases in islet B cell replication in medium with 5.6 mM glucose. Measurement of cAMP levels in the cultures revealed dissociations between effects on B cell replication and insulin release. Thus, addition of 0.1 mM IBMX, or 0.1 nM cholera toxin, to 5.6 mM glucose produced slightly greater increases in cAMP levels and B cell replication than did 16.7 mM glucose, whereas insulin release was increased significantly more with 16.7 mM glucose. Also, addition of 0.1 mM IBMX, or 0.1 nM cholera toxin, to 16.7 mM glucose stimulated further increases in cAMP levels and insulin release in the cultures, but no further increases in B cell replication. We conclude that (a) cAMP stimulates islet B cell replication, (b) cAMP may mediate the effects of glucose on B cell replication, and (c) mechanisms regulating B cell replication may be more sensitive to cAMP and/or different from those regulating insulin secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1980

The evolution of renal osteodystrophy in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Since the introduction of continuous ambulatory peritoneal dialysis by Popovich et al [1] and the subsequent modification of the technique by Oreopoulos et al [2], an increasing number of patients with end-stage renal disease are maintained on this new treatment modality. To date, there has not been any report of the effect of CAPD on the evolution of renal osteodystrophy which is one of the major complications of chronic renal failure. In this report we will present the results of our radiological and biochemical studies of renal osteodystrophy in 28 patients who have been on CAPD from 6 to 23 months.

Adult↗
PubMed1979

Erythropoietin levels in uremic nephric and anephric patients.

Erythropoietin titers were measured in anemic nephric and anephric patients undergoing chronic hemodialysis by utilizing a plasma concentration technique. In eight out of 11 anephric patients studied, decreased but detectable levels of erythropoietin were found, suggesting that extrarenal erythropoietin plays a role in the regulation of red cell production in anephric patients. In 14 nephric uremic patients, erythropoietin production was found to be more variable, with one group of eight patients having erythropoietin levels in the range for normal nonanemic individuals (3.9 to 15 mU/ml), and a second group of six patients with erythropoietin higher than normal (greater than 15 mU/ml). Both groups were found to be equally anemic, indicating that in the second group the bone marrow is less responsive to erythropoietin. The severity of secondary hyperparathyroidism was found to be higher in this second group, suggesting a role of PTH in the bone marrow unresponsiveness. A good correlation between biological and immunological erythropoietin activities was found in the plasma from normal subjects and uremic nephric and anephric patients.

Animals↗
PubMed1978

Speaking fundamental frequency characteristics associated with voice pathologies.

This study investigated the relationship between pathologic and normal speaking fundamental frequency characteristics (SFF) in a group of 80 male subjects. The subjects were divided into four groups of 20 (1) vocal fold paralysis, (2) benign mass lesion, (3) cancer of the larynx, and (4) normal. The results of this study indicate that SFF standard deviation and semitone range of SFF are significantly reduced for patients with vocal fold paralysis as compared with normals. The parameters of mean SFF, number of frequency shifts, and age failed to separate the normals from the three groups of pathologic subjects.

Acoustics↗
PubMed1976

Analgesic abuse nephropathy.

Analgesic abuse nephropathy is seldom considered as a cause in patients presenting with chronic renal disease. In a three-year period 450 patients were seen with chronic renal failure. Of these 103 had interstitial renal disease as the cause of their failure. Twenty of these 103 were due to chronic analgesic abuse, which indicates that need for a greater awareness of this problem. The spectrum of clinical and roentgenographic aspects of analgesic abuse nephropathy are discussed. What constitutes analgesic abuse, helpful clinical findings, frequency of other medical illnesses, and the low incidence of documented renal infection prior to onset of renal failure are discussed. Intravenous pyelographic findings related to visualization, renal size, corticomedullary margins and pelvicalyceal changes are also discussed and demonstrated.

Analgesics↗