Alastair Hay

Factors affecting the transfer of organochlorine pesticide residues to breastmilk.

Existing studies monitoring organochlorine pesticide residues in breastmilk were examined to identify whether common factors determine the extent of transfer of these residues. A structured review of the English language literature was conducted. Papers were reviewed and assessed using a structured protocol. A total of 77 papers were initially identified, 46 of which contained conclusions relating to the factors which may affect the transfer of residues into breastmilk. Owing to the diversity of findings, papers were screened further to include only those in which a minimum of background information relating to selection of mothers and to milk sampling procedures were reported. Only eight papers were deemed to contain adequate information. Age, parity/length of previous lactation, fat mobilisation and the time of sampling were identified as the most likely factors to be considered when assessing transfer of organochlorine pesticide residues into breastmilk. This review highlights the difficulties of assessing trends in breastmilk contaminants where comparable sampling procedures are not used.

Maternal alcohol intake prior to and during pregnancy and risk of adverse birth outcomes: evidence from a British cohort

Background Evidence is conflicting regarding the relationship between low maternal alcohol consumption and birth outcomes. This paper aimed to investigate the association between alcohol intake before and during pregnancy with birth weight and gestational age and to examine the effect of timing of exposure. Methods A prospective cohort in Leeds, UK, of 1303 pregnant women aged 18–45 years. Questionnaires assessed alcohol consumption before pregnancy and for the three trimesters separately. Categories of alcohol consumption were divided into ≤2 units/week and >2 units/week with a non-drinking category as referent. This was related to size at birth and preterm delivery, adjusting for confounders including salivary cotinine as a biomarker of smoking status. Results Nearly two-thirds of women before pregnancy and over half in the first trimester reported alcohol intakes above the Department of Health (UK) guidelines of ≤2 units/week. Associations with birth outcomes were strongest for intakes >2 units/week before pregnancy and in trimesters 1 and 2 compared to non-drinkers. Even women adhering to the guidelines in the first trimester were at significantly higher risk of having babies with lower birth weight, lower birth centile and preterm birth compared to non-drinkers, after adjusting for confounders (p<0.05). Conclusions We found the first trimester to be the period most sensitive to the effect of alcohol on the developing fetus. Women adhering to guidelines in this period were still at increased risk of adverse birth outcomes. Our findings suggest that women should be advised to abstain from alcohol when planning to conceive and throughout pregnancy.

Steady-state pharmacokinetics of methadone in opioid addicts

SummaryKinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions — in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day) — providing unique pharmacokinetic data.Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean Ka, 1.7 h−1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing.The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution — assuming the oral bioavailability (f) of methadone to be 0.95 — was large (mean 6.71 · kg−1).The slow clearance of this drug from the body (mean 3.1 ml · min−1 · kg−1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval.

Carbon monoxide poisoning

The onset of autumn and cooler weather traditionally heralds the start of another season in the northern hemisphere—the peak incidence of unintentional deaths from carbon monoxide. Each year around 50 people in the United Kingdom die from carbon monoxide poisoning, and a year ago the chief medical officer warned again of the dangers.1 As yet there is no evidence that the population is at any lesser risk. Humans have been poisoned by carbon monoxide since they first discovered hydrocarbon fuels, incomplete combustion of which is the usual cause of poisoning. Napoleons surgeon, Larrey, saw soldiers with carbon monoxide induced myonecrosis when billeted in huts heated by woodburning stoves. And over 60 years ago American physicians were warned that chronic carbon monoxide exposure could mimic many neurological conditions, such as “cerebral haemorrhage, encephalitis, multiple sclerosis, spastic paraplegia, chorea and tetany.”2 Throughout the world people continue to die unnecessarily from carbon monoxide exposure or to survive their encounter with disabling symptoms whose cause is misdiagnosed. Carbon monoxide famously binds to haemoglobin over 200 times more strongly than oxygen, a strange evolutionary quirk explained by the tiny amounts of carbon monoxide produced naturally in the body by haem oxygenase and the need to have an efficient scavenging system for such a …

Proteomic Screening of a Cell Line Model of Esophageal Carcinogenesis Identifies Cathepsin D and Aldo-Keto Reductase 1C2 and 1B10 Dysregulation in Barrett’s Esophagus and Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EA) incidence is increasing rapidly and is associated with a poor prognosis. Identifying biomarkers of disease development and progression would be invaluable tools to inform clinical practice. Two-dimensional polyacrylamide gel electrophoresis was used to screen 10 esophageal cell lines representing distinct stages in the development of esophageal cancer. Thirty-three proteins were identified by MALDI-TOF-MS which demonstrated differences in expression across the cell lines. Western blotting and qRT-PCR confirmed increased cathepsin D and aldo-keto reductases 1C2 and 1B10 expression in metaplastic and dysplastic cell lines. Expression of these proteins was further assessed in esophageal epithelium from patients with nonerosive (NERD) and erosive gastro-esophageal reflux disease, Barretts esophagus (BE) and EA. When compared with normal epithelium of NERD patients, (i) cathepsin D mRNA levels demonstrated a stepwise increase in expression (p<0.05) in erosive, metaplastic and EA tissue; (ii) AKR1B10 expression increased (p<0.05) 3- and 9-fold in erosive and Barretts epithelium, respectively; and (iii) AKR1C2 levels increased (p<0.05) in erosive and Barretts epithelium, but were reduced (p<0.05) in EA. These proteins may contribute to disease development via effects on apoptosis, transport of bile acids and retinoid metabolism and should be considered as candidates for further mechanistic and clinical investigations.

Mortality of power workers exposed to phenoxy herbicides and polychlorinated biphenyls in waste transformer oil.

Herbicide spray crews employed by a Canadian power company between 1950 and 1967 had a higher than expected death rate, with a standardized mortality ratio of 157% (CI 130%-194%). In 1991, the cohort consisted of 225 former sprayers of whom 127 were still alive and 98 had died. Eligibility for inclusion in the cohort was based on employer records; and a history of spraying for 30 days or more in at least one spray season. Deaths expected were based on age-specific population mortality rates for New Brunswick. The all-age SMR for the total cohort was 159%. After 1958, however, waste transformer oil was added to the phenoxy-herbicide spray mixture, the oil representing 10% of the final mixture. Spray crews wore no protective clothing. Subdividing the cohort into spray years 1950-1958 and 1959-1967 yielded SMRs of 146% (CI 115%-184%); and 215% (CI 139%-318%), respectively. The transformer oil was used during the period 1959-1967. Most excess deaths were due to cardiovascular disease.

Assessing caffeine exposure in pregnant women

Studies on the effects of caffeine on health, while numerous, have produced inconsistent results. One of the most uncertain and controversial effects is on pregnancy outcome. Studies have produced conflicting results due to a number of methodological variations. The major challenge is the accurate assessment of caffeine intake. The aim of the present study was to explore different methods of assessing caffeine exposure in pregnant women. Twenty-four healthy pregnant women from the UK city of Leeds completed both a detailed questionnaire, the caffeine assessment tool (CAT) designed specifically to assess caffeine intake and a prospective 3 d food and drink diary. The women also provided nine saliva samples over two consecutive days for estimation of caffeine and a metabolite (paraxanthine). Caffeine intakes from the CAT and diary showed adequate agreement (intra-class correlation coefficient of 0.5). For saliva caffeine and paraxanthine measures, the between-sample variation (within the same woman) was greater than between-woman and between-day variation. However, there was still adequate agreement between these measures and the CAT. The CAT is a valuable tool that is now being used in a large prospective study investigating caffeines role in pregnancy outcome.

Benzodiazepine misuse by drug addicts.

Using a high-performance liquid chromatography method, we measured seven commonly prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam, lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients attending the Leeds Addiction Unit. All of the urines selected for investigation were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen. Forty-four of the urines contained a range of benzodiazepines, none of which had been prescribed. Nitrazepam was detected most frequently (61 urine samples), but had not been prescribed to any of the patients in this study. Chlordiazepoxide was detected in 49 urine samples, although it had been prescribed to only five patients. Temazepam was detected in 28 urine samples. Fourteen patients providing 21 urine samples had been prescribed temazepam for treatment. However, temazepam was detected in only 14 of these samples. Multiple benzodiazepine abuse was evident from the high rate of detection of unrelated benzodiazepines.

Identification, characterisation, and measurement of immunoglobulin concentrations in grey (Haliocherus grypus) and common (Phoca vitulina) seals

Concentrations of macroglobulin, total gammaglobulin, and a gammaglobulin subclass were measured in grey and common seals. In pups, immunoglobulin M (IgM) was found to rise rapidly, concentrations reaching adult values by approximately 14 days postpartum. Total IgG concentrations increased more slowly, only approaching 50% of juvenile and adult male values by 30 days after birth. Concentrations of the IgG subclass did not change significantly postpartum. Total IgG concentrations measured in adult female grey seals sampled during lactation were found to be lower than in males and juveniles. This apparent immunosuppression may be associated with pregnancy.

A Rapid Horizontal TLC Method for Detecting Drugs of Abuse

We present a rapid, low-cost method for detecting opioids, cocaine and amphetamine in the urine of drug abusers. Rapid solid phase extraction of 2 mL of urine using octadecylsilane cartridges (Bond Elut C18) concentrates compounds of interest (including the polar metabolite of cocaine, benzoylecgonine), in a small volume of methanol, which is easily dried down. Four microlitres of aliquots of samples and standards are spotted on to 5 cm square polyester-backed silica gel plates, and developed (8–10 min) in a Desaga H-Chamber. Rf values of all relevant compounds are presented for two mobile phases using an iodoplatinate spray. The sensitivity of the method is not the same for all drugs but is always at least 1 µg/mL urine. A number of investigations can be performed on a single extract from 2 mL of urine including confirmatory tests using different solvent systems or sprays.