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Biomedical subjects

W H Mullen

Publications and source records attributed to W H Mullen.

7 recordsLinked to original sources

Incorrect overdose management advice in the Physicians' Desk Reference.

STUDY HYPOTHESIS: Physicians may consult references such as Physicians' Desk Reference (PDR) for overdose management advice. Although PDR recommendations are approved by the US Food and Drug Administration (FDA), we hypothesized that they are often outdated and potentially hazardous. METHODS: We surveyed physicians who consulted our poison center during a 1-month period with regard to their use of the PDR for overdose information and also compared PDR overdose treatment recommendations with those of five current major toxicology references. For the PDR overdose information review we examined data from the American Association of Poison Control Centers to identify pharmaceutical categories with the largest number of deaths. We reviewed the four leading drugs with at least 1,000 reported exposures in each category and identified 20 PDR-listed brand-name products for analysis. We obtained the consensus from five current toxicology references on contraindicated treatments, ineffective treatments, and specific recommended treatments or antidotes. Finally, we compared the overdose management advice provided in the 1994 PDR with the toxicology reference consensus. RESULTS: Forty of 80 of physicians surveyed (50%) reported use of the PDR for overdose information in the preceding 12 months. Of the 20 PDR entries, 16 (80%) had at least one deficiency, and 5 (25%) had two or more deficiencies. Thirteen (65%) omitted an indicated specific treatment, three (15%) recommended contraindicated treatments, and four (20%) advised ineffective treatments with potential for harm. Only four entries (20%) had no deficiencies by our survey criteria. CONCLUSION: We found serious discrepancies in overdose treatment advice in the PDR compared with a consensus of current toxicology references. Altogether, four of five PDR entries were deficient, and almost half advised ineffective or frankly contraindicated therapies. Despite FDA approval, the use of PDR overdose advice in a serious poisoning case could result in unnecessary morbidity or mortality.

Drug Information Services↗

Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature.

BACKGROUND: Pennyroyal is a widely available herb that has long been used as an abortifacient despite its potentially lethal hepatotoxic effects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported. OBJECTIVES: To quantify pennyroyal metabolites in human overdose, to correlate these findings with clinical variables, and to place these findings in the context of previously reported cases of pennyroyal toxicity. DESIGN: Clinical case series of pennyroyal ingestions; quantification of pennyroyal metabolites by gas chromatography and mass spectrometry; qualitative detection of protein-bound adducts of the metabolites of pennyroyal constituents in human liver by Western blot assay; and review of the literature based on a search of MEDLINE, Index Medicus, and the reference citations of all available publications. RESULTS: We report four cases of pennyroyal ingestion. One patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N-acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil. CONCLUSION: Pennyroyal continues to be an herbal toxin of public health importance. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine. Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted access to the herb.

Acetylcysteine↗

Homogeneous amperometric immunoassay for theophylline in whole blood.

A homogeneous spectrophotometric EMIT immunoassay kit for the quantitation of theophylline in serum or plasma has been modified to produce a rapid, amperometric immunoassay requiring a 50 microliters whole blood sample. The basis of the detection system for the assay is the electrochemical oxidation of NADH produced by G6PDH-labelled theophylline at a potential of +150 mV vs Ag/AgCl using platinised activated carbon (PACE) electrodes. Comparison of the amperometric whole blood method with the conventional spectrophotometric plasma assay produced a reasonable correlation: y = 0.90x - 1.01, (r = 0.98, n = 12). The advantage of the new method is that simple and robust instrumentation can rapidly determine theophylline in whole blood with no sample pre-treatment or separation steps.

Biosensing Techniques↗

Enzyme electrode for the measurement of lactate in undiluted blood.

An enzyme electrode is described based upon the enzyme lactate oxidase (EC 1.1.3.2) coupled to an H2O2 sensor. Use of an organosilane-treated microporous membrane over the enzyme layer, allows responses linear to 18 mmol/l L-lactate with response times of 1-3 min, whilst giving independence from stirring. The method is suitable for the bedside analysis of a single drop of undiluted whole blood. Correlation with a routine method gave y = 0.96x + 0.11, r = 0.996, n = 46.

Cellulose↗

Needle enzyme electrodes for biological studies.

Needle enzyme electrodes have been produced for measurement of glucose and lactate. They comprise glutaraldehyde-crosslinked oxidases immobilised over less than 1.1 mm od needle-type sensors for H2O2. To obtain selectivity in blood, an underlying polyethersulphone membrane was used which excluded electrochemical interferents from the working (Pt) electrode. Linearity for the systems was extended to cover the clinical range by the use of outer low permeability polyurethane membranes. This type of external membrane also reduced the stirring dependence of electrodes. The glucose needle electrode was used in unstirred whole blood samples and gave an acceptable correlation with the routine spectrophotometric method (y = 0.954x + 0.202, r = 0.991, n = 48).

Blood Glucose↗