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Biomedical subjects

A Murphy

Publications and source records attributed to A Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Invasive streptococcal infections. Report of four cases occurring in Trinidad.

Many countries are reporting a resurgence of virulent streptococcal strains but there is little information from the Caribbean. Four cases of severe invasive streptococcal infections, three of them fatal, are reported. The portal of entry was infected scabatic lesions in one patient and infected mosquito bites in another patient who developed cellulitis and gangrene; but no portal of entry was detected in the other patients. Group A beta haemolytic Streptococcus (GAS) was isolated from the blood of three patients, one of them GAS M type 3, which had the genome for streptococcal pyrogenic exotoxins A (SPeA) and B (SPeB). GAS M type 72, which had the genome for SPeB and SPeC, were isolated from the tissues (but not from the blood) of the patient who developed cellulitis and who was the sole survivor. Physicians in the Caribbean must be alerted to the presence of these virulent streptococcal strains, and must be prepared to manage serious invasive disease.

Adult↗
PubMed1997

Cardiac fibroma presenting as sudden death in a six-month-old infant.

Cardiac fibroma is a rare benign tumour which occurs predominantly in infancy and childhood. We present the case of a six-month-old female infant who died suddenly at home and was found at autopsy to have a large cardiac fibroma in the ventricular septum. The tumour was apparently asymptomatic although there was evidence of mild cardiac failure. Death was thought to be due to a fatal arrhythmia.

Death, Sudden, Cardiac↗
PubMed1997

Disposition and metabolism of olanzapine in mice, dogs, and rhesus monkeys.

Olanzapine (OLZ) is a novel antipsychotic agent with a high affinity for serotonin (5-HT2), dopamine (D1/D2/D4), muscarinic (m1-m5), adrenergic (alpha 1), and histamine (H1) receptors. The pharmacokinetics, excretion, and metabolism of OLZ were studied in CD-1 mice, beagle dogs, and rhesus monkeys after a single oral and/or intravenous dose of [14C]OLZ. After oral administration, OLZ was well absorbed in dogs (absolute bioavailability of 73%) and to the extent of at least 55% in monkeys and 32% in mice. The terminal elimination half-life of OLZ was relatively short in mice and monkeys (approximately 3 hr) and long in dogs (approximately 9 hr). In mice and dogs, radioactivity was predominantly eliminated in feces; but, in monkeys, the major route of elimination of radioactivity was urine. Dogs and monkeys excreted in urine, respectively, 38% and 55% of the dose over a 168-hr period, whereas the fraction of the dose excreted in urine of mice over the collection period (120 hr) was 32%. OLZ was subject to substantial first-pass metabolism; at the tmax, OLZ accounted for 19%, 18%, and 8% of the radioactivity, in mice, dogs, and monkeys, respectively. The ratio of AUC OLZ to AUC radioactivity was, respectively, 10%, 14%, and 4% in mice, dogs, and monkeys. The principal urinary metabolites in mice were 7-hydroxy OLZ glucuronide, 2-hydroxymethyl OLZ, and 2-carboxy OLZ accounting for approximately 10%, 4%, and 2% of the dose. Metabolites that were present in urine in lesser amounts were 7-hydroxy OLZ, N-desmethyl OLZ, and N-desmethyl-2-hydroxymethyl OLZ. In dogs, the major metabolite accounting for approximately 8% of the dose was 7-hydroxy-N-oxide OLZ. Other metabolites identified were 2-hydroxymethyl OLZ, 2-carboxy OLZ, N-oxide OLZ, 7-hydroxy OLZ, and its glucuronide and N-desmethyl OLZ. The major metabolite in monkey urine was N-desmethyl-2-carboxy OLZ, and accounted for approximately 17% of the dose. In addition, N-oxide-2-hydroxymethyl, 2-carboxyl OLZ, and 2-hydroxymethyl OLZ were identified in monkey urine. Thus, in mice and dogs, OLZ was metabolized through aromatic hydroxylation, allylic oxidation, N-dealkylation, and N-oxidation reactions. In monkeys, OLZ was biotransformed mainly through double oxidation reactions involving the allylic carbon and methyl piperazine nitrogen. Whereas the oxidative metabolic profile of OLZ in animals was similar to that of humans, animals were notable for not forming appreciable amounts of the principal human metabolite (i.e. 10-N-glucuronide OLZ).

Administration, Oral↗
PubMed1996

Zidovudine absorption and small intestinal function in HIV seropositive patients.

Zidovudine absorption was evaluated in HIV seropositive patients with (n = 15) and without diarrhoea (n = 20) in a standardised prospective pharmacokinetic study using single oral 200 mg doses. Zidovudine was rapidly absorbed with large peak variation (Cmax: 1.10 +/- 0.43 mg/L). There were no significant associations between pharmacokinetic parameters and presence of diarrhoea, CD4 counts, red blood cell folate concentrations, stool cultures/leucocytes or the lactulose/mannitol absorption test. Mean diarrhoea AUC (mg/L.h) was 1.13 +/- 0.30 and 1.07 +/- 0.36 in non-diarrhoeal patients. Antidiarrhoeals increased AUC and Cmax values in a small, non statistically significant subset of diarrhoea patients. Although zidovudine absorption varies significantly, our data do not support dosage individualisation based on any of the above parameters.

Administration, Oral↗
PubMed1996

An investigation into the physical stability of a neonatal parenteral nutrition formulation.

The physical stability of a neonatal parenteral nutrition formulation has been examined using differential interference contrast (DIC) microscopy. In vitro studies indicated that particle size increases occur immediately after mixing the Intralipid emulsion with the amino acid/glucose solution, while simulation of clinical administration indicated that larger droplets were observed at the end of the catheter approximately 1 h after administration commenced. Microscopic observation of adjacent droplets of the two fluids showed reversible aggregation occurring almost immediately. It was concluded that the current method of administering this neonatal emulsion does not prevent droplet coalescence.

Drug Stability↗
PubMed1996

Bypassing the ribosome: peptide synthesis without translation.

Chemical peptide synthesis is well-established but has drawbacks, notably the need to protect side-chain functional groups during reactions. Proteolytic enzymes may be used 'in reverse' to catalyse peptide synthesis without side-chain protection and avoiding the danger of racemization. Enzymic syntheses may use either an equilibrium or a kinetic strategy. Equilibrium synthesis is simply the reversal of hydrolysis, using any type of protease. Kinetic synthesis involves time-dependent acyl transfer using activated substrates and a serine or cysteine protease. Enzymic synthesis often takes place in partially aqueous or non-aqueous reaction media; the medium can often desirably influence the protease's properties. It is possible to tailor a protease to improve its usefulness in peptide synthesis; one can alter the enzyme's properties by means such as chemical modification, PEG-coupling or protein engineering.

Binding Sites↗
PubMed1995

Leukocyte function-associated antigen 1 (LFA-1) and CD44 are signalling molecules for cytoskeleton-dependent morphological changes in activated T cells.

Signaling through the leukocyte function-associated antigen 1 (LFA-1) molecule has previously been shown to induce homotypic aggregation in T cells and to induce cytoskeletal changes in T lymphoma cells. In this study we describe the induction of a dendritic phenotype associated with cytoskeletal rearrangement in activated human peripheral blood T cells stimulated with monoclonal antibody SPV-L7 to LFA-1 alpha. Maximal expression of this phenotype required 72 h preactivation with phorbol myristate acetate and expression was abolished using the protein kinase C inhibitor staurosporine. Monoclonal antibody to CD18, the beta-chain of LFA-1, did not induce this phenotype. Monoclonal antibody MEM 83 to presumably a discrete epitope on LFA-1 alpha did not induce this phenotype but induced homotypic aggregation. However, a monoclonal antibody to CD44 induced a similar phenotype in activated lymphocytes. Induction of both homotypic in activated lymphocytes. Induction of both homotypic aggregation and the dendritic phenotype was abolished by preincubation with soluble intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal inhibitors prevented the morphological changes in SPV-L7-activated lymphocytes. Preincubation with tyrosine kinase inhibitor, protein kinase C inhibitors, and inhibitors of new protein synthesis also prevented these morphological changes. These data suggest that discrete epitopes on LFA-1 alpha may be capable of inducing discrete signals either for homotypic aggregation or for a dendritic phenotype. As both LFA-1 and CD44 are involved in the migration of lymphocytes through high endothelial venules, these data could suggest that these molecules transduce signals resulting in cytoskeletal modification necessary for lymphocyte transmigration.

Alkaloids↗
PubMed1995

Soft-tissue sarcomas of the shoulder girdle: factors influencing local recurrence distant metastases, and survival.

BACKGROUND: Prognostic factors and the role of radiotherapy have not been well characterized for soft-tissue sarcomas (STS) of the shoulder girdle. METHODS: The cases of 70 patients with primary shoulder STS were reviewed for the following information: size, grade and histology of tumors, extent of resection, and use of adjuvant radiotherapy. The influence of these factors on local disease-free survival (LDFS), distant disease-free survival (DDFS), and overall survival (OS) rates was analyzed using univariate analysis. RESULTS: With a median follow-up of 108 months, the overall 5- and 10-year survival rates for patients with shoulder girdle STS were 82% and 80%, respectively, whereas the 5-year disease-free survival rate was 63%. There were 25 (35%) tumor recurrences: 12 (17%) distant and 13 (18%) local regional. Tumors > 5 cm in size were associated with a significantly decreased 5-year OS rate compared with lesions < 5 cm, and high-grade tumors were associated with significantly decreased DDFS and OS rates. Because most of the patients who underwent amputation had large, high-grade tumors, they had significantly decreased 5-year DDFS and OS rates compared with wide local excision. Radiotherapy produced a significant improvement in LDFS rates, particularly in patients with tumors > 5 cm in size. CONCLUSIONS: The results indicate that both tumor size and grade are important prognostic factors in shoulder girdle STS. Adjuvant radiotherapy should be considered in large tumors to improve the LDFS and to decrease the need for radical ablative surgery.

Adolescent↗
PubMed1995

In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication.

Fabrication of the sampling lumen of an intra-arterial PO2 sensor is performed in standard catheters mechanically or by laser. Clinical evaluation is performed with respect to catheter insertion, complications, accuracy of oxygen sensor data and fibrin deposition on the catheter surface. The success rate for catheter insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The proportion of catheter failures (blocked or non-reading) is 14% in laser-cut compared with 30% in standard. These differences are not statistically significant at the 5% level. There is no clinically significant difference in sensor accuracy, with 37.5% of results within +/- 0.05 kPa and 80% within +/- 2.0 kPa of simultaneous blood gas values. Drift is within +/- 0.3 kPa h-1 for 78% of monitoring time. Significant errors of recalibration occur in 6% of calibrations. Scanning electron micrographs demonstrate a much smaller sampling lumen in the laser-cut group, but no reduction in fibrin deposition at the site of the sampling hole. The low success rate for catheter insertion is a problem because of cost implications. The accuracy of the system is usually sufficient for clinical purposes, provided the calibration is checked every 4 h.

Catheterization, Peripheral↗
PubMed1995

A prospective randomized trial to evaluate different oral dose regimens of medroxyprogesterone acetate in women with advanced breast cancer.

A prospective randomized study was conducted to try to answer two questions: is a loading dose of medroxyprogesterone acetate (1000 mg p.o. q.d.s. for 48 h) superior to conventional dosing; and does an oral maintenance dose of 1000 mg daily offer any advantage over 500 mg daily in women with advanced breast cancer who have failed to respond to, or have relapsed after, tamoxifen? Of 211 patients randomized, 207 were evaluable. There was no improvement in response rates, time to response, response duration or overall survival as a result of the loading dose. When comparing high and low maintenance doses, there was a significant difference in response rates (48% versus 32%; chi 2 = 10.09, df = 2, P = 0.006) and survival (66% versus 41% alive at 12 months; chi 2 = 9.06, df = 1, P = 0.003) in favour of the higher dose regimen, although there was no significant difference in the duration of response. There was no additional toxicity attributable to the loading dose regimen, but side effects were more frequent with the high dose maintenance schedule (141 of 201 adverse effects occurring in these two groups) although the incidence of severe toxicity was similar with both high dose and low dose treatments.

Administration, Oral↗
PubMed1995

Comparison of metallothionein gene expression and nonprotein thiols in ten Arabidopsis ecotypes. Correlation with copper tolerance.

Seedlings of 10 Arabidopsis ecotypes were compared with respect to copper tolerance, expression of two metallothionein genes (MT1 and MT2), and nonprotein thiol levels. MT1 was uniformly expressed in all treatments, and MT2 was copper inducible in all 10 ecotypes. MT1 and MT2 mRNA levels were compared with various growth parameters for the 10 ecotypes in the presence of 40 microM Cu2+. The best correlation (R = 0.99) was obtained between MT2 mRNA and the rate of root extension. MT2 mRNA levels also paralleled the recovery phase following inhibition by copper. Induction of MT2 mRNA was initiated at copper concentrations below the threshold for growth inhibition. In cross-induction experiments, Ag+, Cd2+, Zn2+, Ni2+, and heat shock all induced significant levels of MT2 gene expression, whereas Al3+ and salicylic acid did not. The correlation between copper tolerance and nonprotein thiol levels in the 10 ecotypes was not statistically significant. However, 2 ecotypes, Ws and Enkheim, previously shown to exhibit an acclimation response, had the highest levels of nonprotein thiols. We conclude that MT2 gene expression may be the primary determinant of ecotypic differences in the copper tolerance of nonpretreated Arabidopsis seedlings.

Arabidopsis↗
PubMed1995

Expression of CD44 on rheumatoid synovial fluid lymphocytes.

OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.

Arthritis, Rheumatoid↗