Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.

Single-dose disulfiram does not inhibit CYP2A6 activity.

BACKGROUND: Disulfiram and its primary metabolite diethyldithiocarbamate are effective mechanism-based inhibitors of human liver cytochrome P450 2E1 (CYP2E1) in vitro. A single dose of disulfiram, which significantly diminishes human P450 2E1 activity in vivo, has been used to investigate the role of CYP2E1 in human drug metabolism and to prevent CYP2E1-mediated biotransformation. Nevertheless, the specificity of single-dose disulfiram toward human CYP2E1 in vivo is unknown. Because diethyldithiocarbamate also inhibits human liver CYP2A6 in vitro, this investigation explored the effect of single-dose disulfiram on human CYP2A6 activity in vivo. METHODS: CYP2A6 activity was assessed by the 7-hydroxylation of coumarin, which is catalyzed selectively by CYP2A6. Ten healthy volunteers received 50 mg oral coumarin on two occasions in a randomized crossover design, approximately 10 hours after 500 mg oral disulfiram was administered or after no pretreatment (control group). Plasma and urine 7-hydroxycoumarin and plasma coumarin concentrations were determined by HPLC. RESULTS: The area under the plasma 7-hydroxycoumarin versus time curve (2.69 +/- 0.90 micrograms.hr/ml) was not decreased after disulfiram pretreatment (3.33 +/- 0.93 micrograms.hr/ml). Furthermore, maximum plasma concentration (Cmax) of 7-hydroxycoumarin (1.4 +/- 0.5 versus 1.8 +/- 0.6 micrograms/ml) and time to reach Cmax (1.0 +/- 0.2 and 1.0 +/- 0.4 hour) were unchanged by disulfiram pretreatment. Urinary 7-hydroxycoumarin excretion over a 24-hour period (38.9 +/- 10.8 mg) was also undiminished by disulfiram pretreatment (45.2 +/- 6.6 mg). CONCLUSIONS: Single-dose disulfiram does not inhibit human CYP2A6 activity in vivo. When single-dose disulfiram is used as an in vivo probe for P450, inhibition of drug metabolism suggests involvement of CYP2E1 but not CYP2A6.

The British hepatic angiosarcoma register.

A register of British cases of primary hepatic angiosarcoma (HAS) was established in 1974 to monitor the occurrence of cases from 1963 onwards. Details of cases dying in 1963-77 have been obtained. Thirty-five cases were agreed as HAS by panel of liver pathologists, and occupational and medical information was obtained in the majority of these. Two cases were attributable to VCM exposure, and eight others had received intra-arterial Thorotrast. In 1978-79, two more cases were confirmed in VCM polymerization workers.

An apparatus for the determination of volatile analytes by stopped-flow injection analysis using an integrated fiber optic detector.

A new method for the analysis of volatile analytes using a stopped-flow injection system originating from either a gas or liquid phase has been developed. It uses an integrated fiber optic detector which also serves as a reactor. This system combines the advantages of gas diffusion and stopped-flow, making the overall assay very sensitive. Both gas streams and aqueous solutions containing ammonia were analyzed. The limits of detection are 40 ppb for gas phase analysis and 1.0 ppm for aqueous phase analysis.

Rectal indomethacin for postoperative pain in orthopaedic surgery. A double-blind study.

We report a double-blind study of the effectiveness of indomethacin suppositories in the relief of postoperative pain and the reduction in demand for opiate analgesia following orthopaedic procedures.

Biological monitoring of occupational exposure in the chromate pigment production industry.

A survey of occupational exposure to hexavalent chromium in chromate pigment production was undertaken in factories producing lead chromate (PbCrO4) and strontium chromate (SrCrO4). Sampling pre and post-shift in a factory where SrCrO4 production had just started showed the optimum strategy for biological monitoring is the measurement of urinary chromium, in urine samples taken at the end of Friday shift and pre-shift the following Monday. However, short-term uptake may be assessed under these circumstances by the increase in urinary chromium over a shift. Body burden, representing long-term chromate exposure is best assessed by measuring chromium in whole blood or pre-shift urinary chromium at the beginning of the working week. Exceptionally high levels of chromium in blood (387-4160 nmol l-1) and urine (41-1250 nmol nmol-1 creatinine) as well as skin and nasal lesions, were discovered amongst the workforce at the strontium chromate plant. These contrasted with occupationally unexposed levels of less than 20 nmol l-1 and less than 1 nmol nmol-1 creatinine, respectively, and led to the continuation of the biological monitoring programme. At the same time, improved working practices and respiratory protection equipment were introduced. A steady elimination of chromium from whole blood with a half-life of approximately 24 days was found. This elimination rate was confirmed over a 14 day period when the workforce were completely removed from exposure. The study confirms the usefulness of biological monitoring in assessing the uptake of hexavalent chromium and control of exposure.

Mount St. Helens eruptions: the acute respiratory effects of volcanic ash in a North American community.

After the May 18, 1980 volcanic eruption of Mount St. Helens, increases were observed in the number of patients who, because of asthma or bronchitis, sought medical care at emergency rooms of major hospitals in areas of ashfall. An interview study of 39 asthma and 44 bronchitis patients who became sick during the 4 wk following the eruption and who attended the emergency rooms of two major hospitals in Yakima, Washington, and of healthy matched controls indicated that a history of asthma, and possibly of bronchitis, were risk factors for contracting respiratory problems. The interview study also indicated that the main exacerbating factor was the elevated level of airborne total suspended particulates (in excess of 30,000 micrograms/m3) after the eruption. An interview study of 97 patients who had chronic lung disease and who lived in the same area as the above-mentioned patients, but who did not go to a hospital, showed that the ashfall exacerbated the condition in about one-third of these. Emergency planners and their geologist advisers should be aware that special preventive measures are justified for people with a history of asthma or chronic lung disease who live in communities at risk to volcanic ashfalls.

Lake Nyos disaster, Cameroon, 1986: the medical effects of large scale emission of carbon dioxide?

Carbon dioxide was blamed for the deaths of around 1700 people in Cameroon, west Africa, in 1986 when a massive release of gas occurred from Lake Nyos, a volcanic crater lake. The clinical findings in 845 survivors seen at or admitted to hospital were compatible with exposure to an asphyxiant gas. Rescuers noted cutaneous erythema and bullae on an unknown proportion of corpses and 161 (19%) survivors treated in hospital; though these lesions were initially believed to be burns from acidic gases, further investigation suggested that they were associated with coma states caused by exposure to carbon dioxide in air. The disaster at Lake Nyos and a similar event at Lake Monoun, Cameroon, two years previously provide new information on the possible medical effects of large scale emissions of carbon dioxide, though the presence of other toxic factors in these gas releases cannot be excluded.

Exposure to antineoplastic drugs in two UK hospital pharmacy units.

STUDY OBJECTIVES: To carry out an environmental and biological monitoring study in two UK hospital pharmacy units involved in the preparation of antineoplastic drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug preparation. One used isolators operating at positive pressure relative to external atmospheric pressure, whereas the other used negative pressure isolators. Monitoring utilized the measurements of methotrexate, ifosfamide, cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples were collected together with preshift and post-shift urine samples over a 4-day consecutive monitoring period. During the study period both units operated to their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were detected on the floors of both units and on the disposable gloves worn by staff preparing the drugs. There was also evidence in both units of some very low-level drug absorption from urine measurements, using the most sensitive analytical technique of platinum analysis. The absorption of platinum containing drugs in the unit using negative-pressure isolators was significantly higher, even though less platinum containing drug was prepared per day. Urine measurements in both units were below the detection limit for the other measured drugs. Although the unit using positive-pressure isolators handled daily approximately five times the drug quantities handled with the negative pressure unit, the general levels of external contamination and urine measurements did not reflect this difference. Comparison of the relative levels of glove and floor contamination between the two units was not clear-cut and appeared to depend on the specific cytotoxic drug being monitored. CONCLUSIONS: The levels of external contamination on the floor and gloves, and absorbed dose from urine measurements found in this study showed considerable improvement over many earlier, non-UK studies using comparable exposure measurements. These earlier studies were in facilities using laminar flow/microbiological safety cabinets and where staff were likely to be involved in both drug preparation and administration. Our data did not suggest that the differential pressure of the isolator to the pharmacy atmosphere was an overarching factor in the risk of operator exposure under normal operation. There remains a need to investigate the sources of the low-level drug contamination found in the pharmacies even when using isolators to prepare cytotoxic drugs. This study, and related studies of hospital oncology ward staff, appear to be the only recent UK studies of occupational cytotoxic drug exposure using environmental and biological monitoring techniques.

Responding to major toxic releases.

Major releases of hazardous substances into the community are a preventable cause of disaster. Despite the impetus given by recent legislation to emergency planning the problems of mounting an adequate response to a chemical disaster are considerable. The successful medical management of a major incident depends upon a rapid and complete evaluation of the acute and possible long-term health hazards and this is likely to require the urgent deployment to the scene of specialists from the key disciplines. Some of the lessons of previous major incidents are highlighted; these are similar regardless of the route of human exposure (air, food and drink, water) or whether the release is from an industrial or natural source.

Research in occupational health. The UK National Health Service.

The creation of over fifty consultant posts in occupational medicine in the National Health Service in the last few years has paved the way for the development of occupational health research in the health services in the United Kingdom. General research topics that await further study include: health inequalities amongst health care workers, the Sick Doctor and Sick Nurse; job stress, back problems, pregnancy, and infection risks from blood. Topical specific hazards include glutaraldehyde, cytotoxic drugs, nuclear magnetic resonance imaging, and implications of new technology in surgery. The coordination of databases across different district health authorities would create large populations for epidemiological research, such as the surveillance of sentinel diseases, the delivery of occupational health services and vaccination strategies. Occupational health should be seen as an integral part of delivering health care and adequate funding for occupational health research should be made available.

Rehydration of desiccated Baralyme prevents carbon monoxide formation from desflurane in an anesthesia machine.

BACKGROUND: Desiccated carbon dioxide absorbents degrade desflurane, enflurane, and isoflurane to carbon monoxide (CO) in vitro and in anesthesia machines, which can result in significant clinical CO exposure. Carbon monoxide formation is highest from desflurane, and greater with Baralyme than with soda lime. Degradation is inversely related to absorbent water content, and thus the greatest CO concentrations occur with desflurane and fully desiccated Baralyme. This investigation tested the hypothesis that rehydrating desiccated absorbent can diminish CO formation. METHODS: Baralyme was dried to constant weight. Carbon monoxide formation from desflurane and desiccated Baralyme was determined in sealed 20.7-ml vials without adding water, after adding 10% of the normal water content (1.3% water), and after adding 100% of the normal water content (13% water) to the dry absorbent. Similar measurements were made using an anesthesia machine and circle system. Carbon monoxide was measured by gas chromatography-mass spectrometry. RESULTS: Carbon monoxide formation from desflurane in vitro was decreased from 10,700 ppm with desiccated Baralyme to 715 ppm and less than 100 ppm, respectively, when 1.3% and 13% water were added. Complete rehydration also decreased CO formation from enflurane and isoflurane to undetectable concentrations. Desflurane degradation in an anesthesia machine produced 2,500 ppm CO in the circuit, which was reduced to less than 180 ppm when the full complement of water (13%) was added to the dried absorbent. CONCLUSIONS: Desflurane is degraded by desiccated Baralyme in an anesthesia machine, resulting in CO formation. Adding water to dried Baralyme is an effective means of reducing CO formation and the risk of intraoperative CO poisoning. Although demonstrated specifically for desflurane and Baralyme, rehydration is also applicable to enflurane and isoflurane, and to soda lime.

Infection risks in hospital staff from blood: hazardous injury rates and acceptance of hepatitis B immunization.

A questionnaire survey of 1800 clinical health care staff was undertaken to determine hazardous injury rates and uptake of hepatitis B vaccination. The overall sharps injury rate was 116 injuries per 100 staff per year. Full-time doctors had the highest rates. Surgical procedures were the commonest cause of accidental injury (58 per cent) and 30 per cent of all sharps injuries were attributable to careless handling. Injuries caused by bites and scratches from patients occurred mainly in nurses and auxilliaries in psychiatric and geriatric wards (115/100 staff per year). Twenty-four per cent of respondents had received a full course of hepatitis B vaccine and 51 per cent of the remainder were planning to have, or were in the process of receiving, a course. The most frequent reason given for not being vaccinated was lack of information about vaccination. This survey reveals injury rates higher than those observed in previous reports, particularly in doctors, and shows a need for more information and advice about hepatitis B infection and vaccination to be targeted to health care workers at risk.

Occupation and cancer in London: an investigation into nasal and bladder cancer using the Cancer Atlas.

The Atlas of Cancer Mortality for England and Wales showed pronounced excesses of male mortality from nasal and bladder cancer in certain London boroughs. These excesses were investigated by case-referent studies using death certificate data for male deaths, 1968-78. Nasal cancer was found to be significantly associated with occupations involving heavy exposure to wood dust. Bladder cancer was significantly associated with occupations in road transport driving and in the handling of leather, whereas consistently raised relative risk ratios were also found for wood-workers, engineering fitters, printers, machinists, plumbers, and motor mechanics. These findings highlight the potential role of occupational factors in cancer causation in London.

Volcanic ash and respiratory symptoms in children on the island of Montserrat, British West Indies.

BACKGROUND: In July 1995 the volcano on the West Indian island of Montserrat erupted after being inactive for several hundred years. Since then, clouds of ash have been released intermittently from the volcano. Some of this ash is <10 micro m in diameter and therefore respirable. Concerns were raised that the particles might cause respiratory problems. AIMS: To evaluate whether ashfalls had any effect on the respiratory health of children in Montserrat. METHODS: A survey of asthma diagnoses, respiratory symptoms, exercise induced bronchoconstriction (EIB), and current and previous exposure to volcanic ash was carried out in schools in Montserrat during February 1998. RESULTS: Questionnaire information was available for nearly 80% of the 443 children on the school rolls. The prevalence of wheeze symptoms in the previous 12 months was 18% in children aged 12 years and under and 16% in children aged 13 years and over. In children aged 12 and under, the prevalence of wheeze was greater in those who had ever been heavily or moderately exposed to volcanic ash compared with the group who had only ever been exposed to low levels (wheeze in last 12 months: odds ratio (OR) 4.30; wheeze ever: OR 3.45). The prevalence of EIB in 8-12 year olds was about four times higher in those who were currently heavily exposed to volcanic ash (OR 3.85) compared to those currently exposed to low levels. CONCLUSIONS: Volcanic ash emissions adversely affected the respiratory health of Montserrat children. The findings emphasise the need to limit exposures of children to volcanic ash and ensure the appropriate management of respiratory symptoms.

Flow injection microscopy: a novel tool for the study of cellular response and drug discovery.

Studying responses of live cells to agonists, antagonists and other physical stimuli offers insight into their complex membrane and internal biochemistry. An experimental technique has been developed in which responses of living cells in an inverted radial flow chamber are continuously monitored while being repeatedly stimulated using controlled pulses of a biologically active ligand. Precisely defined flow conditions result in reproducible peaks which can be numerically analysed by comparison with a tracer curve obtained by substituting a dye for the stimulus. Exploratory studies have demonstrated that the flow injection technique can provide a novel method for kinetics of receptor binding and cellular responses. Flow injection microscopy (FIM) allows identification of biologically active ligands and their ranking based on measurement of the cellular responses in a short time frame. The use of FIM for rapid drug screening, through monitoring of the initial kinetics of cellular responses, is demonstrated on a model system.

The laryngeal mask airway: a comparison between two insertion techniques.

UNLABELLED: The purpose of the study was to compare the ease of insertion of the laryngeal mask airway using the standard uninflated approach or with a fully inflated cuff. Two hundred consecutive patients undergoing anesthesia using a laryngeal mask airway were randomized to have the laryngeal mask inserted using either method. Successful insertion was judged primarily by the clinical function of the airway. The number of insertion attempts to achieve a satisfactory airway and whether an alternative technique was required for success were recorded. On removal of the laryngeal mask, a blind observer noted the presence or absence of blood. Just before leaving the recovery room, each patient was asked whether they had a sore throat. Insertion technique made no difference with regard to first attempt success. However, the presence of blood on the removed masks (P < 0.01) and sore throat (P < 0.01) were less frequent in the inflated cuff group. We conclude that the inflated cuff insertion technique is an acceptable alternative to the standard approach and has the advantage of reducing the incidence of minor pharyngeal mucosal trauma, as evidenced by mucosal bleeding and sore throat. IMPLICATIONS: Insertion of the laryngeal mask airway with the cuff fully inflated is equally successful to the standard uninflated approach in experienced hands. The inflated technique was associated with less minor pharyngeal mucosal trauma and, consequently, a lower incidence of postoperative sore throat. This implies that the inflated technique would be acceptable to the general population of laryngeal mask users.

Preventive health measures in volcanic eruptions.

Medical treatment has only a small role in severe volcanic eruptions and so preventive measures are paramount if injuries and loss of life are to be reduced. The health team must be incorporated in emergency planning and response at the earliest stage. Guidance on the interpretation of geological information about a volcano and the appropriate health measures that should be adopted before and after an eruption are summarized for the benefit of health workers.