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Biomedical subjects

M McDonald

Publications and source records attributed to M McDonald.

At least 55 records · Page 3Linked to original sources
PubMed1999

Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl.

1. There are differences between the excitotoxic actions of quinolinic acid and N-methyl-D-aspartate (NMDA) which suggest that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors. The present study was designed to examine the effect of a potent antioxidant, melatonin, and the potential neuroprotectant, deprenyl, as inhibitors of quinolinic acid-induced brain damage. Injections were made into the hippocampus of anaesthetized rats, which were allowed to recover before the brains were taken for histology and the counting of surviving neurones. 2. Quinolinic acid (120 nmols) induced damage to the pyramidal cell layer, which was prevented by the co-administration of melatonin (5 nmols locally plus 2x20 mg kg(-1) i.p.). This protective effect was not prevented by the melatonin receptor blocker luzindole. Neuronal damage produced by NMDA (120 nmols) was not prevented by melatonin. 3. Quinolinic acid increased the formation of lipid peroxidation products from hippocampal tissue and this effect was prevented by melatonin. 4. Deprenyl also prevented quinolinic acid-induced damage at a dose of 50 nmols but not 10 nmols plus 2x1.0 mg kg(-1) i.p. The non-selective monoamine oxidase inhibitor nialamide (10 and 50 nmols plus 2x25 mg kg(-1)) did not afford protection. 5. The results suggest that quinolinic acid-induced neuronal damage can be prevented by a receptor-independent action of melatonin and deprenyl, agents which can act as a potent free radical scavenger and can increase the activity of endogenous antioxidant enzymes respectively. This suggests that free radical formation contributes significantly to quinolinic acid-induced damage in vivo.

Animals↗
PubMed1999

Clonally unrelated BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronic myeloid leukemia.

We report a patient with Philadelphia (Ph)-positive, BCR-ABL rearrangement positive, chronic myeloid leukemia (CML) with a prolonged chronic phase of 24 years who was first prescribed alpha-2 interferon 22 years after initial diagnosis. This therapy was tolerated poorly on account of thrombocytopenia, but an eventual major cytogenetic response was followed soon afterwards by transformation to terminal acute myeloid leukemia (AML). Cytogenetic studies indicated that the transformed myeloblasts were karyotypically normal and Ph negative. Although polymerase chain reaction (PCR) analysis of total leukemic mRNA remained BCR-ABL positive, other molecular studies, including Southern blotting and fluorescent in situ hybridization (FISH) analyses, showed that myeloblasts were BCR-ABL rearrangement negative. PCR-based clonality studies using an X-chromosome-linked restriction fragment polymorphism within the phosphoglycerate kinase gene (PGK1) further showed that the Ph-negative blast cells had a different clonal origin from the Ph-positive clone of chronic phase. We suggest that cases of underlying Ph-negative leukemic transformation in Ph-positive CML warrant further study and should be considered for trial of intensive remission induction therapy as appropriate for acute leukemia.

Acute Disease↗
PubMed1999

Acoustic detections of singing humpback whales (Megaptera novaeangliae) in the eastern North Pacific during their northbound migration.

Numerous (84) acoustic detections of singing humpback whales were made during a spring (08 March-09 June 1997) research cruise to study sperm whales in the central and eastern North Pacific. Over 15,000 km of track-line was surveyed acoustically using a towed hydrophone array. Additionally, 83 sonobuoys were deployed throughout the study area. Detection rates were greatest in late March, near the Hawaiian Islands, and in early April, northeast of the islands. Only one detection was made after April. Detection rates for sonobuoys were unequal in three equally divided longitudinal regions of the study area. Two high density clusters of detections occurred approximately 1200-2000 km northeast of the Hawaiian Islands and were attributed to a large aggregation of migrating animals. The distribution of these detections corroborates findings of previous studies. It is possible that these animals were maintaining acoustic contact during migration. Two unexpected clusters of singing whales were detected approximately 900 to 1000 km west of central and southern California. The location of these detections may indicate a previously undocumented migration route between an offshore breeding area, such as the Revillagigedo Islands, Mexico, and possible feeding areas in the western North Pacific or Bering Sea.

Acoustics↗
PubMed1998

A comparison of DNA amplification, isolation and serology for the detection of Chlamydia psittaci infection in cats.

Chlamydia psittaci is a significant cause of conjunctivitis in cats, but can be difficult to diagnose owing to the small number of organisms in conjunctival swabs. In the United Kingdom laboratory diagnosis is based on three techniques: isolation of the infectious organism, amplification of chlamydial DNA by the polymerase chain reaction (PCR) or the detection of anti-chlamydial antibodies by immunofluorescence assay. To determine the most sensitive method these techniques were compared in the field. The PCR based on previously published protocols was less sensitive than isolation, but by modifying the protocol its sensitivity was increased by a factor of 25 to 1250 and it was then more sensitive than isolation. The modified PCR detected chlamydia in samples containing non-infectious organisms. Serology was of limited use in predicting which cats shed C psittaci although seronegative cats were negative by PCR and isolation. The modified PCR was the most sensitive and robust method for confirming C psittaci infection in cases of conjunctivitis in pet cats.

Animals↗
PubMed1998

The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu5Ac2en.

We have previously described a 4-guanidino-Neu5Ac2en (zanamivir)-resistant neuraminidase (NA) variant G70C4-G, with an active site mutation Glu 119 to Gly. This variant has been found to also harbor a hemagglutinin (HA) mutation in the receptor binding site, Ser 186 to Phe. Examination of early passages of the G70C4-G virus revealed that this HA mutation had arisen by the first passage. From a subsequent passage two transient variants were isolated which had each acquired a different second HA mutation, Ser 165 to Asn and Lys 222 to Thr. Both were highly drug resistant and drug dependent and their ability to adsorb to and penetrate cells was decreased. Comparison of drug sensitivities between the variant, with the additional HA mutation at Ser 165, and viruses with either mutation alone revealed that these two HA mutations acted synergistically to increase resistance. To determine the contribution to resistance of each of the NA and HA mutations in G70C4-G, the NA mutation was separated from the HA mutation by reassorting. The NA mutation and the HA mutation each conferred low-level resistance to zanamivir, while the two mutations interacted synergistically in the double mutant to give higher resistance in vitro. Infectivity was not adversely affected in the double mutant and while there was a small decrease in sensitivity to zanamivir in the mouse model, there was no detectable resistance to zanamivir in the ferret model.

Animals↗
PubMed1998

Antiarrhythmic drug effects on QT interval dispersion in patients undergoing electropharmacologic testing for ventricular tachycardia and fibrillation.

The effects of antiarrhythmic drugs on QT interval dispersion as a predictor of antiarrhythmic drug therapy has not been rigorously assessed. This study was performed to determine whether the effects of antiarrhythmic drugs on QT interval dispersion predict antiarrhythmic drug response in patients undergoing electropharmacologic testing for ventricular tachycardiarrythmias. Precordial QT intervals and QT interval dispersions were measured at baseline and during steady-state antiarrhythmic drug therapy in 72 consecutive patients with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained ventricular tachyarrhythmias who underwent electropharmacologic studies to assess arrhythmia suppression. QT interval dispersion was similar at baseline in drug responders (42 +/- 21 ms) and drug nonresponders (46 +/- 21 ms), whereas during antiarrhythmic therapy QT interval dispersion was shorter in drug responders (33 +/- 15 ms) than in drug nonresponders (55 +/- 29 ms, p <0.001). QT interval dispersion was shorter in 7 drug responders during their effective drug trials (27 +/- 14 ms) than during their ineffective drug trials (47 +/- 24 ms, n = 9, p <0.05). QT dispersion < or = 50 ms (p <0.002) and a patent infarct-related artery (p <0.003) were independent predictors of antiarrhythmic therapy. The positive and negative predictive value of QT interval dispersion during drug therapy to predict a successful drug response was 32% and 96%, respectively. QT interval dispersion predicted the outcome of electropharmacologic studies independent of infarct-related artery patency. QT interval dispersion >50 ms during drug therapy was associated with ineffective drug therapy.

Aged↗
PubMed1998

Case management at Warringal Private Hospital: challenges of development, implementation and evaluation.

Case management has the potential to improve the quality of care for patients, streamline efficiencies within organisations, and ultimately lower health care expenditure. This article explores why Warringal Private Hospital embraced the concept and how the chosen model of case management was developed. It describes the implementation and evaluation of the model and how it was received, accepted, and applied by the various stakeholders. The cardiac and orthopaedic units will be cited as case studies in order to emphasise some of the challenges encountered in this process as well as the successful outcomes. It should be noted, however, that each unit within the hospital is unique and, although the principles of case management have been applied throughout the hospital, the development, implementation and evaluation has been specific to each unit.

Case Management↗
PubMed1998

Factors affecting the use of perches in cages by laying hens.

1. Three experiments were carried out with ISA Brown laying hens housed in individual cages with softwood perches of rectangular cross section fitted across the width of each cage, to investigate factors affecting the tendency of hens to lay their eggs from the perches and to use perches at other times. These factors were perch width and angle and method of perch introduction. 2. In experiment 1 there were 4 treatments. Perches were 38 or 60 mm wide; half of each width were flat and half were fixed at 8 degrees, parallel to the slope of the floor. In 2 similar trials (with 48 and 44 birds respectively, equally divided between treatments) birds were moved to experimental cages already fitted with perches. Birds with 38 mm, sloping perches laid less than one third of their eggs from the perch (31% and 9% in the two trials) while those with the other designs laid more than 80% from the perch. Narrow sloping perches were not otherwise aversive and there was no consistent variation between treatments in total time perching. 3. In experiment 2, 32 birds were allowed to start laying on the floor of the experimental cages then perches were introduced at 24 weeks with 8 birds on each of 4 treatments: 50 mm perches fixed flat and 38 mm perches fixed flat, and at 5 and 10 degrees respectively. Only 27% of eggs were laid from the perches with no variation between treatments either in this behaviour or in total time perching. 4. Experiment 3 provided 24 of the birds from experiment 2 with double-length perches to determine whether they showed preferences for the design features under consideration. Either half the perch length was flat and half sloping at 10 degrees or half was 38 and half 50 mm wide. Again a relatively low proportion of eggs was laid from the perches (18%) and birds showed no significant preference for different perch designs as indicated by either how much they perched or where they perched. 5. These results suggest that both perch design and the way pullets are introduced to perches influence the proportion of perch-laid eggs. They confirm that in some circumstances laying from perches can be a serious problem, but that in other circumstances incidence can be reduced to a manageable frequency. Perches may therefore be practical in commercial production without increasing the number of cracked eggs. The results are also likely to be applicable in cages with other facilities including nest boxes.

Animals↗
PubMed1998

Identification of multiple forms of 180-kDa ribosome receptor in human cells.

Herein, we describe the analysis and mapping of cDNA clones encoding variant forms of the human homolog of the canine 180-kDa ribosome receptor (p180). One form, similar to the chicken ES/130 homolog, possesses a large uninterrupted C-terminal region composed predominantly of heptad repeats predicted to form an alpha-helical double-stranded coiled-coil rod. Other forms contain in addition a 10-amino acid consensus motif, NQGKKAEGAQ, repeated up to 54 times in tandem close to the N-terminus. Such repeats in canine p180 represent a ribosome-binding domain. The cDNA hybridized to a major 6-kb transcript in all tissues examined, where very high expression was observed in tissues that carry out a high level of secretion such as pancreas, liver, and placenta. The ES130/p180 gene was mapped to chromosome 20p12, and a potential pseudogene appears to reside on chromosome 7. In summary, the data suggest that p180 exists in humans in different forms because of complete removal of tandem repeats, or partial intraexonic splicing, creating different repeat lengths with potentially novel ribosome-binding characteristics.

Alternative Splicing↗
PubMed1998

Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review.

BACKGROUND: Single-dose antimicrobial prophylaxis for major surgery is a widely accepted principle; recommendations have been based on laboratory studies and numerous clinical trials published in the last 25 years. In practice, single-dose prophylaxis has not been universally accepted and multiple-dose regimens are still used in some centres. Moreover, the principle has recently been challenged by the results of an Australian study of vascular surgery. The aim of this current systematic review is to determine the overall efficacy of single versus multiple-dose antimicrobial prophylaxis for major surgery and across surgical disciplines. METHODS: Relevant studies were identified in the medical literature using the MEDLINE database and other search strategies. Trials included in the review were prospective and randomized, had the same antimicrobial in each treatment arm and were published in English. Rates of postoperative surgical site infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with 95% confidence intervals (95% CI)] calculated. Data were then combined using fixed and random effects models to provide an overall figure. In this context, a high value for the combined OR, with 95% CI > 1.0, indicates superiority of multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear advantage of one regimen over another. Further subgroup analyses were also performed. RESULTS: Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of either single or multiple-dose regimens in preventing SSI. Likewise, subgroup analysis showed no statistically significant differences associated with type of antimicrobial used (beta-lactam vs other), blinded wound assessment, length of the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and gynaecological vs other). CONCLUSIONS: Continued use of single-dose antimicrobial prophylaxis for major surgery is recommended. Further studies are required, especially in previously neglected surgical disciplines.

Anti-Bacterial Agents↗
PubMed1998

Cytokine gene expression in normal human lymphocytes in response to stimulation.

Sequential gene expression of two type 1 cytokines (interleukin 2 [IL-2] and gamma interferon), one type 2 cytokine (IL-10), two monokines (IL-6 and tumor necrosis factor alpha), and one cytokine receptor (IL-2 receptor [IL-2R]) in normal human peripheral blood mononuclear cells (PBMC) following in vitro stimulation was investigated by reverse transcription-PCR methods. Two stimuli were utilized: phytohemagglutinin (PHA), which acts on the CD2 molecule and T-cell receptors, and anti-CD3 monoclonal antibody, which acts on the CD3 molecule and on T-cell receptors. Increased expression of all studied genes occurred between 1 and 4 hours after stimulation, except for that of the gene encoding IL-10, which was delayed. Expression of all but one of the genes was transient, with a maximal mRNA accumulation at about 8 h on average. IL-2R mRNA expression was an exception, showing a prolonged increase (72 h). The general profiles of expression of the five cytokine genes were similar but not identical, suggesting some shared regulatory mechanisms. When responses to four additional stimuli (pokeweed mitogen, Candida albicans, and IL-2 at high and low doses) were compared, similar profiles of cytokine gene expression were found. Thus, the various stimuli caused induction of all cytokines with quantitative, not qualitative, differences. Altogether, the present data are useful for defining the kinetics of gene expression for key cytokines in response to standard immune-cell stimuli.

Antibodies, Monoclonal↗
PubMed1998

Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors.

The influenza virus neuraminidase (NA)-specific inhibitor zanamivir (4-guanidino-Neu5Ac2en) is effective in humans when administered topically within the respiratory tract. The search for compounds with altered pharmacological properties has led to the identification of a novel series of influenza virus NA inhibitors in which the triol group of zanamivir has been replaced by a hydrophobic group linked by a carboxamide at the 6 position (6-carboxamide). NWS/G70C variants generated in vitro, with decreased sensitivity to 6-carboxamide, contained hemagglutinin (HA) and/or NA mutations. HA mutants bound with a decreased efficiency to the cellular receptor and were cross-resistant to all the NA inhibitors tested. The NA mutation, an Arg-to-Lys mutation, was in a previously conserved site, Arg292, which forms part of a triarginyl cluster in the catalytic site. In enzyme assays, the NA was equally resistant to zanamivir and 4-amino-Neu5Ac2en but showed greater resistance to 6-carboxamide and was most resistant to a new carbocyclic NA inhibitor, GS4071, which also has a hydrophobic side chain at the 6 position. Consistent with enzyme assays, the lowest resistance in cell culture was seen to zanamivir, more resistance was seen to 6-carboxamide, and the greatest resistance was seen to GS4071. Substrate binding and enzyme activity were also decreased in the mutant, and consequently, virus replication in both plaque assays and liquid culture was compromised. Altered binding of the hydrophobic side chain at the 6 position or the triol group could account for the decreased binding of both the NA inhibitors and substrate.

Acetamides↗