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Biomedical subjects

Murray Barclay

Publications and source records attributed to Murray Barclay.

12 recordsLinked to original sources
PubMed2006

The use of low dose methotrexate in rheumatoid arthritis - are we entering a new era of therapeutic drug monitoring and pharmacogenomics?

Methotrexate (MTX) is one of the most commonly used medications in the treatment of rheumatoid arthritis (RA). It has proven efficacy as a sole agent as well as in combination with other disease modifying anti-rheumatic agents (DMARDs) including the newer biological agents. MTX is generally well tolerated although there are a number of potentially serious adverse effects. Of these, haematopoietic suppression, hepatotoxicity and pulmonary toxicity are the more severe and patients are therefore required to have appropriate monitoring while they remain on MTX. In the past, attempts at therapeutic drug monitoring using serum MTX concentrations have been unsuccessful. However, MTX is taken into red blood cells (RBC) where up to four glutamates are added to form MTX polyglutamates (MTXPG(n)). More recently it has been suggested that higher RBC MTXPG(3-5) concentrations may be associated with improved disease control. Genetic variations in enzymes involved in the uptake of MTX into cells and its metabolism are also being examined for their ability to predict drug response and potential for adverse events. While it is unlikely that a single genetic variant will predict efficacy or toxicity there is preliminary evidence that a "pharmacogenetic index" that takes into account the effects of multiple genetic variants maybe useful. Although in their infancy at present, both therapeutic drug monitoring using MTXPG concentrations and pharmacogenomics of MTX may prove useful in the future and are worthy of further investigation.

Antirheumatic Agents↗
PubMed2006

Ambulatory oesophageal manometry and pH monitoring for investigation of chest pain: a New Zealand experience.

AIMS: Patients with chest pain of uncertain origin are often referred to gastroenterology to assess for possible oesophageal causes. Oesophageal spasm is difficult to ascertain with stationary manometry, as pain seldom occurs during this brief study. Twenty-four-hour ambulatory manometry and oesophageal pH recording (AMP) offers the opportunity to correlate pain symptoms with abnormal motility or acid reflux for more definitive diagnosis. AMP has been available at Christchurch Hospital since 2000 and we describe our experience. METHODS: Thirty-seven patients (23 female, 14 male) underwent AMP between January 2000 and January 2004. Tracings were analysed by automated software and manually by an experienced scientist and gastroenterologist. Case-notes were reviewed for history and drug data. RESULTS: Thirty-three patients (89%) experienced typical pain and/or dysphagia symptoms during AMP. Twenty-one had no correlation between symptoms and pH or manometric abnormalities, excluding reflux disease or an oesophageal hypercontractile disorder as a cause of symptoms. Only one patient had oesophageal spasm proven. One patient's pain correlated strongly with acid reflux. Seven others had reflux episodes during AMP with less consistent pain correlation. At least six patients required treatment for ischaemic heart disease after a negative AMP result. CONCLUSIONS: AMP has been a useful additional investigation for chest pain and was able to exclude oesophageal causes of pain in most patients studied. Oesophageal spasm appears to be a rare cause of chest pain in Christchurch. When a diagnosis was made on AMP, it was most often gastro-oesophageal reflux disease.

Adolescent↗
PubMed2005

Measurement of thiopurine methyl transferase activity guides dose-initiation and prevents toxicity from azathioprine.

AIM: To establish an assay service for thiopurine methyl transferase (TPMT) activity in order to facilitate dose initiation of thiopurine drug therapy and to define appropriate reference intervals and optimal cut-offs for the New Zealand population. METHODS: 407 patients underwent radio-enzymatic assay testing of TPMT activity prior to initiation of thiopurine drug therapy. Those with low activity also underwent genotyping for the abnormal *2, *3A, and *3C alleles. RESULTS: A trimodal distribution of enzyme activity was seen consistent with the known polymorphic genetics for this enzyme. Three cases of homozygous deficiency were identified. The 'normal' range is 9.3 to 17.6 units/ml red blood cells (RBCs), but many heterozygotes have activity above the lower limit of his range. TPMT activity above 10.7 units/ml RBC identifies a normal genotype with 100% probability. CONCLUSION: The normal range for TPMT has been established. The measurement of TPMT activity helps to guide dose initiation and may prevent toxicity from azathioprine.

Azathioprine↗
PubMed2005

Submental surface electromyographic measurement and pharyngeal pressures during normal and effortful swallowing.

OBJECTIVE: To evaluate the influence of 2 swallowing maneuvers on anterior suprahyoid surface electromyographic measurement and pharyngeal manometric pressure. DESIGN: Correlational analysis of biomechanic measures of swallowing. SETTING: Research laboratory in a community hospital. PARTICIPANTS: A consecutive volunteer sample of 22 healthy subjects (mean, 29.7y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak amplitude of submental surface electromyographic and pharyngeal manometric pressure at 3 locations. RESULTS: Effortful swallow generated greater pharyngeal pressure than normal swallow at the 2 proximal pharyngeal sensors (sensor 1: P=.017; sensor 2: P=.009) and lower pressure at the distal sensor (upper esophageal sphincter) (P<.001). Pressure in the upper pharynx was lower than that in the lower pharynx (P=.027). Effortful swallow generated greater surface electromyographic amplitudes than normal swallowing (P<.001). A statistically significant but weak negative correlation was identified between surface electromyographic and mid-pharyngeal pressure for normal swallowing condition (r=-.21, P<.01). For the effortful swallowing condition, statistically significant but weak negative correlations were identified between surface electromyographic and pressure measurements at all sensors (sensor 1: r=-.16, P=.02; sensor 2: r=-.30, P<.01; sensor 3: r=-.18, P<.01). CONCLUSIONS: There is a significant change in both suprahyoid surface electromyographic and pharyngeal pressures during effortful swallow compared with normal swallow.

Adult↗
PubMed2003

Digoxin therapeutic drug monitoring: an audit and review.

AIM: The measurement and assessment of digoxin concentrations are often performed poorly. We have conducted an audit to assess the appropriateness of digoxin therapeutic drug monitoring in Christchurch Hospital. METHODS: One hundred consecutive requests for digoxin concentrations in Christchurch Hospital inpatients were assessed. The case notes and hospital medication records were reviewed to determine the indication for testing, the appropriateness of the sampling time and of the subsequent alteration to dosing. RESULTS: In 53% of requests no clear indication for digoxin therapeutic drug monitoring (TDM) could be determined. In the remainder, 'suspected toxicity' accounted for 31% and 'therapeutic failure' for 16%. Samples were inappropriately taken within eight hours post-dose in 32% of requests. In 19% of cases, the samples did not reflect steady-state conditions. In 5% of occasions, the subsequent decision regarding dose adjustment was felt to be clearly inappropriate, and there was uncertainty regarding appropriateness in some other cases. Overall, in only 29% of requests was TDM performed appropriately with regard to indication, sampling and subsequent dose alteration. CONCLUSIONS: At Christchurch Hospital, the practice of TDM for digoxin is often inappropriate. It would seem that medical staff education is required to improve this practice.

Anti-Arrhythmia Agents↗