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Biomedical subjects

P J Baxter

Publications and source records attributed to P J Baxter.

At least 19 recordsLinked to original sources
PubMed2005

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.

Air Pollution, Indoor↗
PubMed2003

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.

Adolescent↗
PubMed2002

Assessment of the exposure of islanders to ash from the Soufriere Hills volcano, Montserrat, British West Indies.

BACKGROUND AND AIMS: The Soufriere Hills volcano, Montserrat, has been erupting since July 1995 and volcanic ash has fallen on the island throughout most of the eruption. The ash contains substantial quantities of respirable particles and unusually large amounts (15-20%) of the crystalline silica mineral, cristobalite. The purpose of the surveys described here, undertaken between December 1996 and April 2000, was to determine levels of personal exposure of islanders to volcanic ash and cristobalite in order to inform advice on the associated risks to health and the measures required to reduce exposure. METHODS: Surveys of personal exposure to respirable dust and cristobalite were undertaken using cyclone samplers. In addition, direct reading instruments (DUSTTRAK) were used to monitor ambient air concentrations of PM(10) at fixed sites and also to provide information about exposures to airborne particles associated with selected activities. RESULTS: Environmental concentrations of airborne ash have been greatest in the areas where the most ash has been deposited and during dry weather. Individual exposure to airborne ash was related to occupation, with the highest exposures among gardeners, cleaners, roadworkers, and police at roadside checkpoints. During 1997 many of these individuals were exposed to concentrations of cristobalite that exceeded the ACGIH recommended occupational exposure limit. Since the population became confined to the north of the island in October 1997, even those in relatively dusty occupations have received exposures to cristobalite well below this limit. CONCLUSIONS: Most of the 4500 people who have remained on island since the eruption began have not been exposed to sufficiently high concentrations of airborne dust for long enough to be at risk of developing silicosis. However, more than a dozen individuals continued to experience frequent high occupational exposures to volcanic ash, some of whom may have had sufficient exposure to crystalline silica to be at risk of developing mild silicosis. If volcanic activity were to deposit further ash over the occupied areas of the island during the coming years, the risks of silicosis will become more substantial.

Adult↗
PubMed2002

Occupational exposure to cytotoxic drugs in two UK oncology wards.

AIMS: To investigate the potential exposure to cytotoxic drugs of staff on two oncology wards in a large district, UK hospital under normal working conditions. METHODS: Cytotoxic drug exposure was monitored in urine samples, surface wipes, and on disposable gloves by using a number of commonly used marker drugs, namely cyclophosphamide, ifosfamide, methotrexate, and the platino coordinated drugs. Questionnaire data on their work practices, potential exposure, use of protective personal equipment, and relevant training were collected from nursing, domestic, and clerical staff on two oncology wards. RESULTS: The majority of staff were female with a mean age of 31 years. Roughly half of the staff studied were specifically trained nurses with an average of 3.5 years experience of administering cytotoxic drugs. No cytotoxic drug preparation or reconstitution was carried out on the wards. Disposable gloves, plastic armlets and aprons, but not eye protection, were invariably worn where there was potential exposure to cytotoxics. No cytotoxic drug was detected in any of the staff's urine samples. Isolated disposable latex gloves from nurses administering drugs showed some contamination, as did some surfaces within the wards' sluice rooms, but not in the ward areas where the drugs were stored and checked prior to administration. CONCLUSIONS: The risk management strategies in place, including use of personal protective equipment, staff training, and other organisational measures, have ensured that internal exposure is lower than the detection limits for the current biological monitoring methods. Levels of contamination appear significantly lower than earlier, non-UK published studies where different risk management strategies were in place and, in particular, ward staff may have been involved in some degree of cytotoxic drug reconstitution.

Adult↗
PubMed2001

Dry deposition and heavy acid loading in the vicinity of Masaya Volcano, a major sulfur and chlorine source in Nicaragua.

Certain volcanoes constitute the world's largest sources of SO2, HCl, and HF emissions and contribute significantly to regional acid deposition. However, the impact of volcanic acid emissions to nearby ecosystems remain poorly documented. In this paper, the spatial pattern of acid dry depositions was monitored within 44 km of Masaya Volcano, Nicaragua, with a network of sulfation plates. Measured SO2 deposition rates were <2-791 mg m(-2) day(-1). The plates also collected the dry deposition of HCI at rates of <1-297 mg m(-2) day(-1). A similar deposition velocity Vd (gas transfer) of 1.6 +/- 0.8 cm/s was calculated for SO2 and HCl above the plate surfaces. Quantities of SO2 and HCI deposited daily within the area surveyed amounted to 1.5 x 10(8) g and 5.7 x 10(7) g, respectively, which correspond to about 10% of the total SO2 and HCl released by the volcano. These depositions may generate an equivalent hydrogen flux ranging from <1 to 30 mg m(-2) day(-1). Our results demonstrate that volcano emissions can dramatically affect acid deposition downwind and in turn cause extreme acid loading of the local ecosystems. This study opens exciting prospects for investigating the sensivity of volcanic ash soils to acid inputs.

Acid Rain↗
PubMed1998

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.

Administration, Oral↗
PubMed1998

Mechanistic aspects of carbon monoxide formation from volatile anesthetics.

BACKGROUND: Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This investigation examined sequential steps in anesthetic degradation to CO. METHODS: Carbon monoxide formation from anesthetics and desiccated barium hydroxide lime or soda lime was determined at equimole and equiMAC concentrations. Carbon monoxide formation from deuterium-substituted anesthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive chemical intermediate was trapped and identified by gas chromatography-mass spectrometry. The source of the oxygen in CO was identified by 18O incorporation. RESULTS: Desflurane,enflurane,andisoflurane(difluoromethylethyl ethers), but not sevoflurane (monofluoromethyl ether), methoxyflurane (methy-ethyl ether), or halothane (alkane) were degraded to CO. The amount of CO formed was desflurane > or = enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at equimole concentrations. Proton abstraction from the difluoromethoxy carbon was greater with potassium than with sodium hydroxide, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desflurane > isoflurane > or = methoxyflurane = sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution on enflurane and desflurane diminished CO formation. Chemical trapping showed formation of a difluorocarbene intermediate from enflurane and desflurane. Incorporation of H2(18)O in barium hydroxide lime resulted in C18O formation from unlabeled enflurane and desflurane. CONCLUSIONS: A difluoromethoxy group is a structural requirement for haloether degradation to CO. Results are consistent with initial base-catalyzed difluoromethoxy proton abstraction (potassium > sodium hydroxide, thus greater CO formation with barium hydroxide lime vs. soda lime) forming a carbanion (reprotonated by water to regenerate the anesthetic, hence requirements for relatively dry absorbent), carbanion decomposition to a difluorocarbene, and subsequent difluorocarbene reaction to form CO.

Absorption↗
PubMed1997

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.

Anesthesia↗
PubMed1997

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.

Anesthesia, Inhalation↗
PubMed1996

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.

Cell Line↗
PubMed1995

Configurations of a flow injection system for perfusion studies of adherent cells.

This paper describes three configurations of a flow injection apparatus designed to be the fluidic drive for perfusion studies of cultured adherent cells. The apparatus was coupled to a flow-through perfusion chamber that was specifically designed for live cell perfusion using fluorescence microscopy as the detector. The instrument consists of two linear syringe pumps and a multiposition selector valve which, under computer control, allowed sequential injection, fluid switching, and flow injection to be performed with minimal system reconfiguration. When the apparatus is coupled to a dual inlet perfusion chamber, target cells can be exposed to very steep reagent pulses, while the traditional single inlet perfusion chamber allows more flexibility and provides a more gradual increase in reagent concentration. The most significant salient feature of the system is the ability to generate very steep pulses--a desirable feature for cell perfusion studies.

Cell Adhesion↗
PubMed1995

Thetford plastics fire, October 1991: the role of a preventive medical team in chemical incidents.

OBJECTIVES: To review the role of a medical team in the emergency management of a major polyvinyl chloride (PVC) fire in an urban area. METHODS: The district health authority's consultant in communicable disease control (CCDC) was requested to advise on the health impacts of a fire that consumed some 1000 tonnes of plastic, mainly PVC, over 72 hours and which emitted a large smoke plume that threatened the health of local residents and emergency workers alike, constituting one of the largest incidents the local emergency services had dealt with in recent years. A medical team was formed comprising the CCDC, a regional epidemiologist, an occupational physician, and a medical toxicologist. This paper is an account of this team's experience of advising on the medical management of the emergency without having any formally established role or previous training for the task. RESULTS: The main issues requiring the input of the medical team included: the possible products of combustion and their effects on health; the clinical management of those exposed; the alerting of local hospitals to the type of casualties to expect; the special health risks posed to emergency workers, especially the firemen; the need for evacuation of local residents; the risks of contamination of soil, water, and crops; the potential health impact of the plume; and the provision of expert and authoritative advice on the short and long term health implications to the public. Active surveillance systems, which included the local general practitioners and hospitals, were established and air monitoring instigated. The 46 casualties were restricted to emergency personnel who had inadvertently received exposure to the fire smoke: all recovered within 48 hours. Local residents were unharmed. CONCLUSION: The incident showed the need for preventive medical teams trained to fill a formal advisory and investigative role for chemical releases and fires, and which can play an integral part in emergency management.

Disaster Planning↗
PubMed1993

An assessment of exposure to glutaraldehyde in hospitals: typical exposure levels and recommended control measures.

An assessment of exposure to glutaraldehyde in cold sterilisation and x ray development processes was undertaken in 14 locations at six hospitals in south east England. The results obtained indicate that routine exposures of hospital workers to airborne concentrations of the compound are within the current United Kingdom occupational exposure limit of 0.7 mg m-3. There was the potential for skin contact in many of the activities observed and alternative sterilisation and disinfection procedures would have been more appropriate in some situations. Recommendations are made on reducing exposures as the current occupational exposure limit for this compound may not be appropriate.

Disinfection↗