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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 235 records · Page 13Linked to original sources
PubMed1994

Product evaluation and process improvement.

This article discusses how a systematic approach to product selection and evaluation can assist health care personnel. This model considers four tenets: (1) quality, (2) cost, (3) safety, and (4) practitioner choice. An algorithm is utilized to serve as a visual guide for the introduction, trial, and selection of equipment and products. In addition to considering the four tenets, the article discusses the value of an integrated team approach and the importance of involving the staff in the decisions.

Attitude of Health Personnel↗
PubMed1994

Temporal differences in the expression of mRNA for IL-10 and IFN-gamma in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii.

C57BL/10 Sc Sn (B10) mice infected orally with Toxoplasma gondii tissue cysts were killed at regular intervals up to day 116 post infection (p.i.) and their brains excised. These were used either to count the total number of cysts in the brain, for RNA purification or histopathological studies. Mortality levels in a parallel group of T. gondii infected B10 mice were also monitored and regular plasma samples taken to measure specific antibody production. Seventy per cent of mice died within the first 35 days of infection. Thereafter deaths were infrequent. Inflammation in the brain was apparent from day 10 onwards and by day 25 there was widespread astrocyte activation, perivascular cuffing, meningitis and extensive encephalitis. Total cyst numbers increased rapidly from day 15 to day 35 when they peaked. By day 60, however, cyst numbers had dropped dramatically and this decrease continued through to day 116. Using the polymerase chain reaction mRNA transcripts for IFN-gamma were detected from the first time point sampled, day 25 p.i., until the end of the study. Transcripts for IL-10, an inhibitor of IFN-gamma production, release and activity, were not detected until day 70. The predominant antibody detected against T. gondii was IgG2a but not IgG1. Significantly transcripts for IFN-gamma were found in the spleens of infected but not non-infected animals. Our results suggest that an inflammatory response associated with IFN-gamma production in B10 mice eventually controls T. gondii infection. After the cyst burden has dropped dramatically transcripts for IL-10 are detected in the brain, perhaps to suppress inflammation, and limit pathology.

Animals↗
PubMed1994

Decentralization of decision-making in Canada's health system: the Sunnybrook experience.

Though there is a significant literature which notes that physicians are fast becoming organizational members, there has been little research evidence to suggest that the adoption of new management models have actually facilitated their involvement. This study sought to examine whether a conscious effort at decentralizing decisions at the clinical unit level would actually result in increased involvement of physicians and other clinicians in decision-making at that level. Two major surveys examining individual roles and responsibilities and unit relationships with other units were conducted, at two points in time, in a large Canadian tertiary care centre. Results suggest that physicians had experienced an increase in administrative discretion. There was an overall increase of many groups in influencing clinical unit decisions with a perceived decrease in senior management influence in budget administration at the unit level. Lessons learned in conducting this type of research are described.

Analysis of Variance↗
PubMed1994

Denial: coping or cop-out?

Health caregivers working with palliative patients in the home are able to establish closer relationships with these patients than in the palliative hospital setting. Since a familiar and comfortable setting helps set the stage for effective communication, it is not surprising that home care patients and their families often share intimate thoughts and feelings with visiting caregivers. Yet that same closeness can make it more difficult for a home caregiver to accept a patient's denial of impending death. While agreeing that, in theory, denial is a normal defence mechanism, the home caregiver may have become too emotionally involved to appreciate denial as a particular patient's choice.

Adaptation, Psychological↗
PubMed1994

Competitive inhibition of human liver microsomal cytochrome P450 3A-dependent steroid 6 beta-hydroxylation activity by cyclophosphamide and ifosfamide in vitro.

The prodrugs cyclophosphamide (CP) and ifosfamide (IF) are oxidized by hepatic cytochrome P450 (P450) to the active cytotoxic species, phosphoramide mustard. Acrolein (prop-2-enal) is also formed during CP and IF activation in rat liver and has been associated with P450 destruction. Analogous inactivation of human liver P450s by CP or IF could lead to pharmacokinetic interactions with coadministered drugs. The present study investigated the susceptibilities of human hepatic P450s to inhibition and inactivation by CP and IF in vitro. Unlike the situation in rat liver microsomes, total P450 was not decreased after incubation of CP or IF with NADPH and human fractions. However, CP and IF inhibited testosterone 6 beta-hydroxylation mediated by P450s 3A but not P450 1A2-dependent 7-ethylresorufin O-deethylation, P450 2C-dependent tolbutamide methyl hydroxylation or P450 2E1-mediated N-nitrosodimethylamine N-demethylation. Kinetic analysis indicated that the drugs were reversible (competitive) inhibitors of testosterone 6 beta-hydroxylation (Km, 94 +/- 8 microM) in human liver microsomes (KiS, 510 +/- 20 microM and 490 +/- 40 microM for CP and IF, respectively). Time-dependent intensification of the inhibition of the activity by CP or IF did not occur; this supports the observation that P450 was refractory to inactivation. The rates of acrolein formation from CP and IF in human hepatic microsomes (0.76 +/- 0.23 and 0.19 +/- 0.07 nmol min-1 mg-1 of protein, respectively) were only 18% and 10% of the rates estimated in fractions from untreated rat liver (4.20 +/- 0.04 and 1.96 +/- 0.12 nmol min-1 mg-1 of protein, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acrolein↗
PubMed1994

Maintaining effective pressure ulcer prevention programs.

Considered by many health care workers to be an inevitable problem of aging, pressure ulcers are in actuality preventable. The prevention of pressure ulcers is a quality outcome of care. Health care providers are held accountable for following national clinical practice guidelines designed to prevent pressure ulcers and minimize associated morbidity. The experience of one enterostomal therapy department in implementing and maintaining a successful pressure ulcer prevention program is described.

Education, Nursing, Continuing↗
PubMed1993

Binding of active cyclosporins to cyclophilin A and B, complex formation with calcineurin A.

The binding properties of several active and inactive cyclosporins to the major intracellular receptor proteins, cyclophilin A and B, as well as the interaction with the phosphatase calcineurin were investigated by ELISA and by means of a photoaffinity labeled probe (PL-CS). Binding to recombinant human cyclophilin A and B was rapid and saturable, and correlated with the in vitro immunosuppressive activity of cyclosporin derivatives. In the presence of cyclophilin A or B and calcium cyclosporin binds specifically to purified bovine calcineurin. PL-CS labeled only the calcineurin A subunit, but not the B subunit or calmodulin. Calcineurin A binding was competed by active (CsA, CsG or CsM), but not inactive (CsH, CsF) derivatives or the structurally unrelated macrolide immunosuppressant FK506. Ternary complexes containing equimolar ratios of cyclophilin A or B, PL-CS and calcineurin were resolved by chemical-crosslinking. The formation of these complexes was apparently specific, calcium-, but not calmodulin-dependent, and only inhibited by active cyclosporins. In vivo labelling of Jurkat T-cells revealed, that cyclophilin A and calcineurin A are the main labeled proteins, which form complexes in the presence of active cyclosporin. Thus, we demonstrate directly, that active cyclosporins have two recognition sites, which allow the in vivo recognition of cyclophilins and calcineurin A.

Affinity Labels↗
PubMed1993

Restoration of substance P and calcitonin gene-related peptide in dorsal root ganglia and dorsal horn after neonatal sciatic nerve lesion.

Dorsal root ganglion (DRG) neurons decrease their substance P (SP) synthesis after peripheral nerve lesions. Levels in the dorsal horn also decline but return to normal if regeneration is successful. In adults, when regeneration is prevented, recovery of SP in the dorsal horn is slow and incomplete, whereas in newborns, recovery is rapid and complete even though retrograde cell death of DRG neurons is greater than in adults. We have examined the mechanisms that might account for the rapid and complete recovery of SP and calcitonin-gene related peptide (CGRP) in the dorsal horn after peripheral nerve injury in newborns. Peptides were compared in the L4 and L5 DRG and spinal cord segments of normal rats and in rats surviving 6 days to 4 months after sciatic nerve section/ligation within 24 hours of birth. Sciatic nerve section/ligation produced 50% neuron death in L4 and L5 DRGs, but immunocytochemical methods showed that both SP-immunoreactivity (-IR) and CGRP-IR recovered completely in dorsal horn. Radioimmunoassay confirmed that recovery of SP was not an artefact due to shrinkage. beta-Preprotachykinin (PPT)-mRNA hybridization and SP-IR were observed mostly in small neurons; alpha-CGRP-mRNA-hybridized and CGRP-IR neurons were more heterogeneous. The percentage of DRG neurons that contained SP (approximately 25%) or CGRP (approximately 50%) was the same in normal newborn and adult rats. Neither selective cell survival nor change in neuron phenotype was likely to contribute to the recovery seen in the dorsal horn, and DRG neurons ipsilateral to the lesion exhibited the same level of hybridized beta-PPT-mRNA and alpha-CGRP-mRNA as intact DRG neurons. Because neither the constitutive level of expression of the genes nor peptide levels increased above those observed in intact DRG neurons, these mechanisms were also not responsible. Axotomized DRG neurons, however, contributed to recovery. Recovery was also due to sprouting by neurons in intact DRGs rostral and caudal to L4 and L5.

Animals↗
PubMed1993

Clinical disease associated with Trypanosoma theileri infection in a calf in Ireland.

A four-month-old calf had a clinical history of pyrexia, anaemia, weight loss and behavioural abnormality. Clinical examination revealed evidence of regenerative anaemia and a lymphocytosis which was characterised by a relatively large B cell population. The calf deteriorated clinically while under observation and its prescapular and prefemoral lymph nodes became enlarged. Examination of a blood smear revealed the presence of a large number of circulating Trypanasoma theileri. Serological examination showed the presence of the invariant, stage-specific, trypanosome surface antigen, ISG70 and antibodies against ISG70. ISG70 was first identified in the bloodstream forms of Trypanosoma brucei and has not previously been found in T theileri. Clinical recovery was associated with an increase in packed cell volume, a decrease in the levels of circulating anti-ISG70 antibodies and the complete disappearance of circulating ISG70.

Animals↗
PubMed1993

Participation of P450 3A enzymes in rat hepatic microsomal retinoic acid 4-hydroxylation.

Cytochrome P450-mediated 4-hydroxylation is an important pathway in the termination of the biological action of retinoids. Several purified mammalian hepatic P450s have been shown to catalyze the 4-hydroxylation of all-trans-retinoic acid (retinoic acid) in reconstituted enzyme systems, but the nature of the activity in untreated rat liver microsomes has not been defined. In the present study, microsomal retinoic acid 4-hydroxylation was characterized in untreated liver from rats of both sexes and after a series of induction treatments. Thus, dexamethasone and phenobarbital, but not beta-naphthoflavone or dimethyl sulfoxide, increased the activity in male and female rats. An immunoglobulin G (IgG) fraction raised against P450 3A1 decreased the rate of retinoic acid 4-hydroxylation in untreated rat hepatic microsomes, but IgG directed against the P450s 2C11, 2B1, and 2C6 were noninhibitory. In vivo administration of triacetyloleandomycin, which has been shown to form a metabolite intermediate complex with P450 3A, followed by potassium ferricyanide oxidation in vitro, reactivated retinoic acid 4-hydroxylation and androst-4-ene-3,17-dione 6 beta-hydroxylation similarly (to 154 and 152% of the respective activities in the absence of potassium ferricyanide). Finally, exogenous retinoic acid (60 mg/kg ip for three days) markedly increased the rate of retinoic acid 4-hydroxylation in hepatic microsomes from male and female rats (3.8- and 3.7-fold, respectively). This occurred without comparable increases in other P450 activities. Despite these findings, the age- and sex-related profiles of microsomal retinoic acid 4-hydroxylation were clearly different from those measured for other P450 activities. Thus, on the basis of xenobiotic pretreatment, developmental, and immunochemical studies, the enzyme(s) involved in constitutive retinoic acid 4-hydroxylation appears distinct from a number of well-described P450s in untreated and induced rat liver. The data are consistent with the partial involvement of P450(s) from the 3A subfamily in retinoic acid 4-hydroxylation, but it seems clear that P450s 3A1 and 3A2 do not participate in this activity.

Age Factors↗
PubMed1993

Effects of four different processing techniques on the microstructure of potatoes: comparison with fresh samples in the ESEM.

Four common scanning electron microscope (SEM) processing techniques involving freeze-substitution and chemical fixation were compared with fresh unprocessed samples imaged in an environmental scanning electron microscope (ESEM) using small pieces of potato tubers as test specimens. Potato tubers were chosen for this investigation because of their high moisture content and, consequently, the common need for extensive processing for conventional, high vacuum SEM imaging. ESEM results showed that the fresh unprocessed specimens were essentially unaltered, showing clear potato cell structure, morphology, and cell content. However, processed samples showed strong differences to the fresh samples: freeze-substituted specimens showed fine networks of material stretching across the surface of cells. These structures may represent fibrillar material or may be artifact caused during processing. Chemical fixation almost entirely destroyed the microstructure of these potato samples.

Cryopreservation↗
PubMed1993

Proliferation of SP- and 5HT-containing terminals in lamina II of rat spinal cord following dorsal rhizotomy: quantitative EM-immunocytochemical studies.

The density of substance P (SP) and serotonin (5HT) immunoreactivity in laminae I and II of rat spinal cord changes following dorsal rhizotomy in a manner consistent with sprouting by intrinsic SP and descending 5HT systems (Wang et al. J. Comp. Neurol. 304: 555, 1991). In this study we used quantitative EM-immunocytochemistry to examine whether the increase in substance P and serotonin immunoreactivity seen at the light microscopic level was related to increased numbers of SP- and 5HT-containing terminals in lamina II. Dorsal roots were sectioned and their ganglia removed from L1 to S2 unilaterally in 18 rats. After 3 (acute), 10 (subacute), or 60 (chronic) days, rats were perfused, and the L5 segments of the spinal cord were removed and prepared for electron microscopy. Lumbosacral deafferentation completely and permanently eliminated complex terminals in lamina II at L5 but the number of simple terminals increased by 46% compared to the control side. This result was similar to that shown previously in cat (Murray and Goldberger, J. Neurosci. 6: 3205, 1986) and suggested that intact intrinsic systems sprouted to form new terminals to compensate for the terminals lost by deafferentation. Quantitative electron microscopic immunocytochemistry demonstrated that the number of terminals containing SP in deafferented lamina II decreased by 58% at 3 days post-operatively and then increased by 10 days and recovered to normal levels by 60 days. The loss of SP terminals in the acute group is due to the loss of SP-containing dorsal root afferents, while the recovery in the chronic group suggests replacement of lost terminals by intrinsic SP systems. These results therefore indicate that SP-containing terminals show homotypic sprouting in response to complete dorsal root deafferentation. The number of 5HT-containing terminals in lamina II of spinal cord increased by 56% on the deafferented side in the chronic group. The increase in 5HT-containing terminals indicates that descending 5HT systems undergo heterotypic sprouting in response to dorsal rhizotomy.

Animals↗
PubMed1993

Removal of dorsal root afferents prevents retrograde death of axotomized Clarke's nucleus neurons in the cat.

We investigated the effect of axotomy, deafferentation, and deafferentation plus axotomy on cell survival and cell size in Clarke's nucleus of the cat spinal cord. Hemisection of the adult spinal cord at T9 leads to retrograde cell death of 40% of the neurons in Clarke's nucleus at L3, as well as to a reduction in the mean soma size of the survivors. In contrast, deafferentation of Clarke's nucleus neurons by L1-S2 dorsal rhizotomy produces no cell loss and no shrinkage of the somata. These results indicate that dorsal root afferent input is not required for Clarke's nucleus cell survival. To test whether afferents may be required by the 60% of neurons that survive axotomy, we deafferented Clarke's nucleus prior to axotomy. Surprisingly, removal of primary afferents to Clarke's nucleus neurons prior to axotomy prevented the death of all neurons that would normally have died from axotomy. These results suggest that dorsal root afferent input is not required for Clarke's nucleus neuron survival after axotomy and may in fact be toxic to these axotomized neurons. This afferent toxicity is likely to be mediated through the dorsal root afferent neurotransmitter glutamate.

Afferent Pathways↗
PubMed1993

The pathophysiology of Trypanosoma congolense infection in Scottish blackface sheep. Influence of dietary protein.

The intensity of parasitaemia, degree of anaemia, blood biochemical changes and live weight gains were measured in two groups of Scottish Blackface sheep infected experimentally with bloodstream forms of Trypanosoma congolense and given either a high or a low protein diet. It was observed that infected animals on a high protein diet tended to develop a higher intensity of parasitaemia than those on a low protein diet. Both groups of infected sheep exhibited similar degrees of anaemia, but the erythropoietic activity, as judged by the increase in mean corpuscular volume and appearance of normoblasts in the circulation, was significantly greater in animals on a high protein diet. The infected animals on a high protein diet gained weight at a similar rate to their uninfected controls, while those on a low protein diet gained significantly less than their controls between 0 and 70 days after infection. Following treatment with the trypanocidal drug isometamidium chloride, both infected groups recovered from the anaemia. However, the rate of recovery was faster in animals on a high protein diet than in those on a low protein diet. It was concluded that high protein intake ameliorates the adverse effects arising from infection, as assessed by the severity of anaemia and weight changes, and also enhances the rate of recovery following chemotherapy.

Anemia↗