Passive smoking and Parkinson disease

This is the first report of an inverse relationship between passive smoking exposure and Parkinson's disease.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

The treatment of tardive dyskinesia: A systematic review and meta-analysis

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for mete-analysis, Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Metaanalysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects. (C) 1999 Elsevier Science B.V. All rights reserved.

Irreversible change of pore structure of MCM-41 upon hydration at room temperature

The pore structure stability of MCM-41 materials upon hydration/dehydration was studied by XRD, Si-29 MAS NMR, and gravimetric adsorption techniques. Results demonstrated that collapses of the pore structure of MCM-41 occurred upon rehydration at room temperature due to the hydrolysis of the bare Si-O-Si(Al) bonds in the presence of water vapor. Full structure collapses of MCM-41 were found to occur when a MCM-41 sample was left in air for three months. It is also suggested that care must be taken when XRD is used to evaluate the structure property of MCM-41 materials to avoid the possible adverse effects of water vapor.

Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia

The polymorphisms of the important xenobiotic metabolizing enzymes CYP2D6, CYP2C19 and CYP2E1 have been studied extensively in a large number of populations and show significant heterogeneity in the frequency of different alleles/genotypes and in the prevalence of the extensive and poor metabolizer phenotypes, Understanding of inter-ethnic differences in genotypes is important in prediction of either beneficial or adverse effects from therapeutic agents and other xenobiotics. Since no data were available for Australian Aborigines, we investigated the frequencies of alleles and genotypes for CYP2D6, CYP2C19 and CYP2E1 in a population living in the far north of Western Australia. Because of its geographical isolation, this population can serve as a model to study the impact of evolutionary forces on the distribution of different alleles for xenobiotic metabolizing enzymes. Twelve CYP2D6 alleles were analysed, The wild-type allele *1 was the most frequent (85.8%) and the non-functional alleles (*4, *5, *16) had an overall frequency of less than 10%. Only one subject (0.4%) was a poor metabolizer for CYP2D6 because of the genotype *5/*5, For CYP2C19, the frequencies of the *1 (wild-type) and the non-functional (*2 and *3) alleles were 50.2%, 35.5% and 14.3%, respectively. The combined CYP2C19 genotypes (*2/*2, *2/*3 or *3/*3) correspond to a predicted frequency of 25.6% for the CYP2C19 poor metabolizer phenotype, For CYP2E1, only one subject had the rare c2 allele giving an overall allele frequency of 0.2%. For CYP2D6 and CYP2C19, allele frequencies and predicted phenotypes differed significantly from those for Caucasians but were similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allele frequencies for CYP2D6*10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively, Pharmacogenetics 11:69-76 (C) 2001 Lippincott Williams & Wilkins.

Experimental study of the deposition of combustion aerosols in the human respiratory tract

The total deposition of environmental tobacco smoke (ETS), diesel and petrol smoke in the respiratory tract of 14 non-smokers between the ages of 20 and 30 was determined experimentally. A scanning mobility particle sizer (SMPS) measuring a size range of 0.016-0.626 mu m was used to characterise the inhaled and exhaled aerosol during relaxed nasal breathing over a period of 10 min. The ETS, diesel, and petrol particles had average count median diameter (and geometric standard deviation) of 0.183 mu m (1.7), 0.125 mu m (1.7), and 0.069 mu m (1.7), respectively. The average total number deposition of ETS was 36% (standard deviation 10%), of diesel smoke 30% (standard deviation 9%), and of petrol smoke 41% (standard deviation 8%). The analysis of the deposition patterns as a function of particle size for the three aerosols in each individual showed that there is a significant difference between each aerosol for a majority of individuals (12 out of 14). This is an important result as it indicates that differences persist regardless of inter-subject variability. (C) 2005 Elsevier Ltd. All rights reserved.

Use of methotrexate in older patients - A risk-benefit assessment

Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor renal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate for rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastrointestinal complications are the most common adverse effects of methotrexate, but hepatotoxicity, haematological toxicity, pulmonary toxicity, lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported, Decreased renal function as a result of disease and/or aging appears to be an important determinant of hepatic, lymphoproli ferative and haematological toxicity, Concomitant use of low doses of folic acid has been recommended as an approach to limiting toxicity. Interactions between methotrexate and several nonsteroidal anti-inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinations in patients with reduced renal function. More serious toxicities (e.g. pancytopenia) may result when other inhibitors of folate utilisation [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methotrexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests and chest radiography should be performed. Blood counts and liver function tests should be repeated at regular intervals. Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dose methotrexate therapy, and the probability of patients continuing their treatment beyond 5 years is greater than for other slow-acting antirheumatic drugs. Thus, given its sustained clinical utility and relatively predictable toxicity profile, low dose methotrexate is a useful addition to the therapy of RA.

Evaluation of fly ash as a component of potting substrates

A series of laboratory and glasshouse experiments were undertaken to assess the potential for incorporation of fly ash in soilless potting substrates. The physical and chemical properties of a commercially available bark based substrate, the University of California (UC) 1:1 peat:sand mix and a range uf test substrates containing fly ash were characterised. In test mixtures, fly ash was substituted for a portion of either the peat or sand component of the UC mix, at rates of 10, 20, 30 and 50% of the mix volume, Incorporation of fly ash greatly increased the plant available water capacity (10-1500 kPa) of the substrate. However, high pH, increased substrate strength and reduced air-filled porosity were considered adverse effects, particularly at ash rates > 20%. The growth of tomato (Lycopersicon esculentum), petunia (Petunia x hybrida grandiflora) and Boston fern (Nephrolepis exaltata) in the substrates was assessed. Two watering regimes, capillary watering and irregular hosing, were used to identify effects of available water capacity on plant growth, but no effect was identified. Test mixtures containing fly ash as 20% of the substrate volume produced growth equal to that in the UC mix, with substrates containing 10% ash producing significantly greater growth of tomato and petunia. At rates of incorporation > 20% reduced plant growth was attributed to both adverse physical and chemical characteristics of the substrate. As fly ash is available at low cost and can be successfully substituted for a considerable portion of the expensive peat component, its use at low application rates in potting substrates may be desirable from an economic viewpoint.

How the NHMRC got its fingers burnt

On 20 December 1996, Justice J Finn of the Federal Court of Australia handed down his judgment in the case of the Tobacco Institute of Australia (TIA) Ltd and others v the National Health and Medical Research Council (NHMRC) and others. Justice Finn concluded that, in developing its recommendations for control of environmental tobacco smoke, the NHMRC's Working Party on Passive Smoking erred significantly in regard to the consultative procedures that it employed. As the following discussion shows, the legal decision has profound implications for the NHMRC and the provision of expert advice to Australian governments on matters of health and health policy. The discussion has been prepared by three members of the NHMRC Working Party, but reflects their personal views and not necessarily those of the Working Party as a whole or those of the NHMRC.

Management of acute psychostimulant toxicity

Psychostimulants produce a broad range of effects. Adverse effects can exist on a spectrum of severity from minor symptoms to life threatening toxicity. Although regular use or use of high doses increases risk of adverse events, many adverse events requiring emergency intervention may occur even in the naïve user.

Low-level lead exposure and children

The adverse effects of environmental lead exposure on the mental development of young children are well established. There is no safe level of blood lead below which children are not affected. Recent research expands our understanding of the impact of lead exposure continuing into later childhood, as well as its effects on children's behaviour. However, social and other environmental factors also contribute to variance in measures of developmental and behavioural outcomes. Lead is associated with only modest effects on children's development, but is a potentially modifiable risk factor. As environmental exposure to lead declines for the whole population, continued specific attention is needed for children living in industrial areas.

A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis

This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events, We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population, The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization. responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.

Surgical outcomes of a randomized prospective trial involving patients with a proximal femoral fracture

Background: An orthopaedic management/patient-focused care unit (OMPFCU) involving a dedicated orthopaedic-geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures. Methods: The surgical outcomes of the patients were monitored in order to determine whether accelerated rehabilitation had any significant adverse effects on the surgical outcomes, measured by mortality, readmission to hospital, deep wound infection, fracture union delay, mobility and the revision surgery rate. Results: No significant difference was recorded in mortality and morbidity, deep wound infection and revision surgery rates between patients in the Royal Brisbane Hospital OMPFCU and those in standard care in the orthopaedic surgery wards. Conclusion: Accelerated rehabilitation for patients with a proximal femoral fracture in a major teaching hospital can be accomplished safely.

Pulpal heat changes with newly developed resin photopolymerisation systems

Composite resin is a widely-used direct tooth coloured restorative material. Photoactivation of the polymerisation reaction can be achieved by visible blue light from a range of light sources, including halogen lamps, metal halide lamps, plasma arc lamps, and Light Emitting Diode (LED) lights. Concerns have been raised that curing lights may induce a temperature rise that could be detrimental to the vitality of the dental pulp during the act of photoactivation. The present study examined heat changes associated with standardised class V restorations on the buccal surface of extracted premolar teeth, using a curing time of 40 seconds. The independent effects of type of light source, resin shade and remaining tooth thickness were assessed using a matrix experimental design. When a conventional halogen lamp, a metal halide lamp and two different LED lights were compared, it was found that both LED lamps elicited minimal thermal changes at the level of the dental pulp, whereas the halogen lamp induced greater changes and the metal halide lamp caused the greatest thermal insult of all the light sources. These thermal changes were influenced by resin shade, with different patterns for LED versus halogen or halide sources. Thermal stress reduced as the remaining thickness of tooth structure between the pulp and the cavity floor increased. From these results, it is concluded that LED lights produce the least thermal insult during photopolymerisation of composite resins.