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M J Stewart

Publications and source records attributed to M J Stewart.

At least 37 records · Page 2Linked to original sources

Fostering partnerships between peers and professionals.

One of the 5 principles of primary health care is public participation. Partnership between professionals and their clients is compatible with this principle. This article describes how professionals and peers can work together in support group interventions. Examples are cited from 3 intervention studies focused on myocardial infarction survivors and their spouses, parents of children with chronic conditions, and older women with disabilities. Each of the support groups entailed co-leadership by and partnerships between peers and professionals. The article describes the characteristics, roles, and training of peers and professionals; data collection involving peers, professionals, and participants; and pertinent intervention processes. Peers and professionals collaborated as co-leaders and partners in 21 support groups in the 3 studies. Participants expressed satisfaction with the leadership of the support groups. Moreover, professional facilitators and peer facilitators each acknowledged the important role and perspective of the other.

Adult↗

Partial liquid ventilation compared with conventional mechanical ventilation in an experimental model of acute lung injury.

OBJECTIVE: To compare the effects of partial liquid ventilation with conventional mechanical ventilation on oxygenation and pulmonary mechanics in saline lavaged rabbits. METHODS: Following acute lung injury (saline-lavage), rabbits were assigned to continue conventional mechanical ventilation (n = 6) or commence partial liquid ventilation (n = 6). In both groups the inspired oxygen concentration was 100% throughout the study. The target PaCO2 of 40-60 mmHg was accomplished by keeping the tidal volume between 7 and 10 mL/kg. During the study the peak inspiratory pressure was adjusted to maintain the target PaCO2. Arterial blood gases were taken pre-lavage, immediately post-lavage (time = 0) and then hourly for 5 hours. Pulmonary mechanics were estimated by measuring compliance and resistance. Pulmonary function was measured pre-lavage, immediately post-lavage and at 1 and 5 hours. At 5 hours the rabbits were killed and the lungs were removed for histological examination. RESULTS: Baseline PaO2, compliance and resistance were not significantly different between groups. The partial liquid ventilation group had a higher PaO2 and a significantly better oxygenation index one hour after commencing partial liquid ventilation and a significantly higher PaO2 averaged over the three hours post-treatment. There were no significant differences in compliance, resistance or lung damage scores. CONCLUSIONS: In this experimental model of acute lung injury, partial liquid ventilation resulted in immediate and sustained increase in PaO2 over 3 hours without significant change in lung mechanics or histological lung damage.

Journal Article↗

Metal concentrations in plants and urine from patients treated with traditional remedies.

A number of traditional South African herbal remedies which are associated with morbidity and mortality were analysed for selenium, manganese, copper, lead, zinc and mercury content. Few showed high levels of toxic metals, but in these the concentrations were sufficiently high as to cause concern since there is no quality control on the production of these remedies, which are the accepted form of medication for over 80% of the population. Urine samples, obtained from 65 patients admitted to hospital following treatment with a traditional herbal remedy were also analysed for metals. Only a small number of the patients had abnormally high levels of metal excretion. These data suggest that, in contrast to experience with traditional Chinese and Indian preparations, metal contamination from plants seems not to be a problem in traditional South African remedies.

Adult↗

The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors.

Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5' and FP330-3') that bind members of the nuclear receptor superfamily were recently identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift assays using oligonucleotides representing either promoter site and rat liver or cultured cell nuclear extracts. In vitro-translated chicken ovalbumin upstream promoter transcription factor (COUP-TFI), ARP-1, or ErbA-related protein 2 (Ear2) bound both sites. In addition, ARP-1/RXR, COUP-TFI/RXR, and ARP-1/COUP-TFI heterodimers bound the FP330-3' site. Mutagenesis of the FP330-3' site indicated that a DR-1 element was the preferred binding site for these factors. Transfected expression plasmids for these factors suppressed basal expression of reporter constructs containing the FP330-3' sites and the induction of the reporter by RXRalpha plus retinoic acid. Mutation of the two sites increased activity of a construct driven by 600 bp of the ALDH2 promoter in cell lines expressing COUP-TFs. The ALDH2 FP330-3' site appears to represent a complex nuclear receptor response element that is activated by RXRs and HNF-4 but repressed by members of the COUP-TF family.

Aldehyde Dehydrogenase↗

Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6.

Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.

Animals↗

Forensic toxicology in urban South Africa.

BACKGROUND: An analysis has been made of the pattern of deaths due to poisoning in South Africa over the period 1991-1996. METHODS: The database held by the Forensic Science Service Laboratory, covering the period 1991-1996 was analyzed. RESULTS: Agricultural chemicals are a major cause of mortality. Among drugs of abuse, combinations of methaqualone/diphenhydramine and cyclizine/dipipanone contribute a disproportionately high percentage of cases. Metal poisoning is common as are cases of poisoning attributed to remedies prescribed by traditional healers.

Agrochemicals↗

Clinical and analytical aspects of pyrrolizidine poisoning caused by South African traditional medicines.

In a study carried out in two hospitals in South Africa the authors identified 20 children suffering from hepatic veno-occlusive disease thought to be caused by the administration of traditional remedies. The predominant clinical presentation was ascites of various degrees and hepatomegaly. There was a high morbidity and mortality in the young infants, and in those cases who survived and were followed up the clinical pattern was one of progression to cirrhosis and portal hypertension. Pyrrolizidine alkaloid poisoning is one of the causes of the veno-occlusive disease. Therefore there is a need for objective confirmation of this. In four of our cases an on-admission urine specimen was available and in all of these a simple colorimetric screening test confirmed the presence of pyrrolizidine alkaloids. The other cases were admitted from peripheral hospitals and clinics and urine was not obtained until after 72 h, a time at which the levels of pyrrolizidines in urine were below the limit of sensitivity of the screening test. The screening method is helpful for the detection of acute ingestion of pyrrolizidines in large amounts, but is not sufficiently sensitive for the detection of chronic ingestion of smaller amounts. Nevertheless, in those patients who have hepatomegaly and ascites a positive finding of pyrrolizidines is important and may remove the necessity for expensive and invasive investigative measures.

Alanine Transaminase↗

The biochemistry and toxicity of atractyloside: a review.

Atractyloside poisoning is an infrequent but often fatal form of herbal poisoning, which occurs worldwide but especially in Africa and the Mediterranean regions. The primary mechanism of atractyloside poisoning is known to be inhibition of the mitochondrial ADP transporter. Poisoning in humans may present with either acute hepatic or renal pathology and it is possible that there is a second, different mechanism of toxicity to the hepatocyte. Atractyloside in large amounts gives rise to massive necrosis, but in vitro studies have shown that at lower doses cells progress to apoptosis. Simple methods for the detection of atractyloside poisoning are at present restricted to thin-layer chromatography in urine and are useful only in the case of severe poisoning. Immunoassays, high-performance liquid chromatography, nuclear magnetic resonance, and a recently developed high-performance liquid chromatography/mass spectrometry method have yet to be applied to clinical diagnoses. There is at present no treatment, but a fuller understanding of the mechanisms of toxicity may lead to the application of a number of compounds that are effective in vitro.

Animals↗

Failure of thrombolysis by streptokinase: detection with a simple electrocardiographic method.

OBJECTIVE: To determine whether simple, readily applicable ECG criteria will allow early prediction of inadequate (< TIMI 3) flow in the infarct related vessel in patients receiving thrombolytic treatment for acute myocardial infarction; and to determine the success of streptokinase in achieving adequate antegrade flow in the infarct related vessel two hours after starting treatment. DESIGN: Cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 100 sequential patients with acute myocardial infarction. INTERVENTIONS: Coronary angiography two hours after the initiation of thrombolytic treatment, proceeding to rescue angioplasty for inadequate flow in the infarct related vessel where appropriate. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of six ECG criteria for the detection of inadequate antegrade flow in the infarct related vessel. RESULTS: The ECG test that performed best as a positive test for < TIMI 3 flow in the infarct related vessel was < 50% resolution of the ST segment elevation in the worst lead and no accelerated idioventricular rhythm. This had a sensitivity of 81%, specificity of 88%, positive predictive value of 87%, negative predictive value of 83%, and overall accuracy of 85%. CONCLUSIONS: Sensitive, specific, and simple ECG criteria are defined for diagnosing failure of thrombolytic treatment with streptokinase. These allow the early detection of patients at high risk of further adverse events from a persistently occluded vessel. They may be used without recourse to sophisticated equipment or complex analyses. Such patients can then be considered for alternative treatments or enrollment into appropriate research protocols.

Adult↗

Failure of thrombolysis: experience with a policy of early angiography and rescue angioplasty for electrocardiographic evidence of failed thrombolysis.

OBJECTIVE: To assess the outcome of a policy of emergency coronary angiography with or without rescue angioplasty in patients with acute myocardial infarction and ECG evidence of failed reperfusion after thrombolysis. DESIGN: A cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 197 patients with acute myocardial infarction fulfilling a simple ECG criterion of failed reperfusion. INTERVENTIONS: Emergency coronary angiography proceeding to rescue angioplasty for inadequate antegrade flow. MAIN OUTCOME MEASURES: Hospital mortality for all 197 patients; incidence of successful and failed rescue angioplasty; need for additional revascularisation in those receiving rescue angioplasty compared with those not treated in this way. RESULTS: 197 patients had emergency angiography for ECG evidence of failed reperfusion; 156 patients received immediate rescue angioplasty. Overall hospital mortality for those undergoing rescue angioplasty was 11.5%. Rescue angioplasty achieved TIMI 2 (11) or TIMI 3 (124) in 135 patients, who had a hospital mortality of 5.9%. Failure to achieve at least TIMI 2 flow following rescue angioplasty occurred in 21 patients, with a hospital mortality of 48%. In the 41 patients in whom immediate rescue angioplasty was not performed, reinfarction or requirement for revascularisation occurred in 37%. Reinfarction occurred in three patients (1.9%) who had immediate rescue angioplasty. Hospital mortality for the whole cohort was 10.7%. CONCLUSIONS: A policy of emergency coronary angiography proceeding to rescue angioplasty where appropriate reduces mortality in a high risk group to a level less than expected for patients with acute myocardial infarction and ECG evidence of failed reperfusion. Unsuccessful rescue angioplasty is associated with a high mortality.

Angioplasty, Balloon, Coronary↗

Routine analysis of amphetamine class drugs as their naphthaquinone derivatives in human urine by high-performance liquid chromatography.

We describe a simple HPLC method which is suitable for the routine confirmation of immunoassay positive amphetamine urine samples. The precolumn derivisation method employing sodium naphthaquinone-4-sulphonate was found to have adequate sensitivity, selectivity and precision for the measurement of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) at 500 microg/l cutoff level for confirmatory analysis of amphetamines in urine. The specificity of the method is enhanced by detecting the peaks at two different wavelengths. The ratios of the peak heights measured at the two wavelengths were different for each of the 5 amphetamines analysed. There was no interference from other phenylethylamine analogues that are commonly found in "over the counter" preparations. The HPLC method is compared to a commercial TLC system for detecting amphetamines in urine of drug abusers attending drug rehabilitation programmes. The HPLC confirmatory method described is a viable alternative to GC or to the more complex and costly GC-MS techniques for confirming amphetamine, methamphetamine, MDMA, MDA and MDEA in urine of drug abusers especially when used in a clinical care setting.

Amphetamines↗

Drosophila S6 kinase: a regulator of cell size.

Cell proliferation requires cell growth; that is, cells only divide after they reach a critical size. However, the mechanisms by which cells grow and maintain their appropriate size have remained elusive. Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size. These flies had smaller cells rather than fewer cells. The effect was cell-autonomous, displayed throughout larval development, and distinct from that of ribosomal protein mutants (Minutes). Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number.

Animals↗

Structural basis and mechanism of enoyl reductase inhibition by triclosan.

The enoyl-acyl carrier protein reductase (ENR) is involved in bacterial fatty acid biosynthesis and is the target of the antibacterial diazaborine compounds and the front-line antituberculosis drug isoniazid. Recent studies suggest that ENR is also the target for the broad-spectrum biocide triclosan. The 1.75 A crystal structure of EnvM, the ENR from Escherichia coli, in complex with triclosan and NADH reveals that triclosan binds specifically to EnvM. These data provide a molecular mechanism for the antibacterial activity of triclosan and substantiate the hypothesis that its activity results from inhibition of a specific cellular target rather than non-specific disruption of the bacterial cell membrane. This has important implications for the emergence of drug-resistant bacteria, since triclosan is an additive in many personal care products such as toothpastes, mouthwashes and soaps. Based on this structure, rational design of triclosan derivatives is possible which might be effective against recently identified triclosan-resistant bacterial strains.

Anti-Bacterial Agents↗

Findings in fatal cases of poisoning attributed to traditional remedies in South Africa.

An analysis of the Johannesburg forensic database over the years 1991-1995 revealed 206 cases in which a traditional remedy was either stated to be the cause of death or was found to be present in a case of poisoning with an unknown substance. The range of toxins detected was wide, with herbal materials being found in 43% of cases, and pharmaceutical or agri-chemicals in 20% and 33% respectively. Since there are as yet no standard methods for the detection of many herbal remedies or their metabolites, careful analysis, using methods such as HPLC/MS, are mandatory for the correct identification of the true cause in cases of poisoning ascribed to traditional remedies.

Cause of Death↗

Plasma total phenytoin: a possibly misleading test in developing countries.

The use of phenytoin has increased among the rural black population in South Africa, many of whom have albumin concentrations below the accepted reference range of 35-50 g/L, related to a combination of malnutrition and late-presenting renal and hepatic disease. Because albumin concentration has a major effect on the proportion of free phenytoin in the extracellular fluid, we instituted a study of the extent of hypoalbuminemia and of the difference between "total" phenytoin (measured by immunoassay), and "corrected" phenytoin (calculated using the Sheiner-Tozer equation, which is based on a mean albumin of 40 g/L). The differences were significant (higher than 20%) in 37% of patients and led us to propose that in populations in which there is a high proportion of patients who are hypoalbuminemic, it is corrected rather than total phenytoin that should be the value reported.

Anticonvulsants↗