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Biomedical subjects

A P Watson

Publications and source records attributed to A P Watson.

17 recordsLinked to original sources
PubMed1992

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure.

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Age Factors↗
PubMed1992

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release.

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.

Chemical Warfare Agents↗
PubMed1992

Neurological problems presenting to an ophthalmic casualty department.

All patients presenting with neurological problems to an eye hospital casualty department over one year were prospectively studied. A total of 119 patients were identified. The most frequent diagnoses were retrobulbar neuritis (34; 28.5%), sixth cranial nerve palsy (22; 18.5%), third cranial nerve palsy (15; 12.6%) and Adie's tonic pupil (11; 9%). Cranial nerve palsies were most commonly due to diabetes or hypertension (16; 43.2%). Only one intracranial aneurysm was found. Symptoms included blurred vision (52; 43.7%), binocular diplopia (51; 42.8%), and eye pain (27; 22.7%). Fifty patients (42.0%) were referred by a general medical practitioner. Twenty-two (18.5%) were admitted to hospital. Forty-nine skull X-rays were requested and all were normal. Twenty-nine chest X-rays were requested. One (3.4%) showed an abnormality (carcinoma of the bronchus). Neurological patients present to ophthalmic casualty departments because of ophthalmic symptoms. Ophthalmic casualty officers are able to make working diagnoses and to direct patients appropriately. The use of investigations in the casualty department, however, is unlikely to be productive.

Adolescent↗
PubMed1992

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

Animals↗
PubMed1990

Arylamine N-acetyltransferase from fast (C57BL6) and slow (A/J) N-acetylating strains of mice.

Many drugs and xenobiotics which are arylamines or hydrazines are metabolized by N-acetyltransferase. The enzyme is polymorphically expressed in humans and inbred strains of laboratory animals can be classified as fast or slow acetylating strains. N-Acetyltransferase has been partially purified from livers from a fast acetylator, C57BL6, and a slow acetylator, A/J, strain of mouse. The enzyme has been purified 1900- and 955-fold, respectively from the two strains, but still represents less than 20% of the total protein. These studies show that at least 5000-fold purification is required to isolate mouse liver N-acetyltransferase from either strain. During purification, N-acetyltransferase from both strains of mice elute identically as a single peak on ion exchange chromatography. Sucrose density gradient centrifugation of N-acetyltransferase shows partial separation of the activity from A/J mice into two peaks whilst the enzyme from C57BL6 mice migrates as one peak which is distinct from both the major and minor types of N-acetyltransferase in A/J mouse liver. The hydrodynamic parameters of N-acetyltransferase from C57BL6 mice and the major peak of N-acetyltransferase from A/J mice show that these enzymes are likely to be monomers of apparent molecular weights 33,000 +/- 1000 and 30,000 +/- 2000, respectively. These results indicate that the N-acetyltransferase isozymes in liver of these two strains of mice are not identical.

Acetyltransferases↗
PubMed1990

Chlorination, water hardness and serum cholesterol in forty-six Wisconsin communities.

The Wisconsin Heart Health Research Program measured serum lipids and other clinical parameters among residents of 46 neighbouring small communities in central Wisconsin. The purpose of the study was to determine whether distribution of serum lipids, blood pressure or thyroid hormones differed according to the chlorination of water supply, or to its calcium and magnesium content (hardness). This report examines serum lipid levels in relation to the drinking water characteristics chlorination and hardness. Variables measured on individuals included age, education level, alcohol intake, cigarette smoking, dietary fat and dietary calcium. An analysis of covariance was used to estimate effects of chlorination and hardness on each of the serum lipids, with individual variables included as covariates. Among females, serum cholesterol (SC) levels are significantly higher in chlorinated communities than in non-chlorinated communities. Community SC levels are also higher for males in chlorinated communities, on the average, but differences are smaller and not statistically significant. Low density lipoprotein (LDL) cholesterol levels follow a similar pattern to that for total SC levels, higher in chlorinated communities for females, but not different for males. On the other hand, high density lipoprotein (HDL) cholesterol community means are nearly identical in the chlorinated and non-chlorinated communities for each sex.

Adult↗
PubMed1990

Oral fluorescein angiography: reassessment of its relative safety and evaluation of optimum conditions with use of capsules.

Injection of fluorescein intravenously for fundal angiography is associated with a high incidence of minor adverse effects (21%) but a very low incidence of serious (life threatening) reactions (0.05%). A serious reaction may occur without warning in a patient with no history of atopy. There are no reports of oral fluorescein causing a serious reaction, and minor adverse effects are uncommon. A study was undertaken to determine optimum conditions for oral fluorescein angiography. Capsules proved more convenient than a solution for ingestion of fluorescein. A dose of 25 mg/kg body weight produced good quality angiograms in 75% of the patients. The best pictures were obtained by photographing the fundus after 40 and 60 minutes.

Administration, Oral↗
PubMed1990

Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers.

Antidotes↗
PubMed1989

Disposing of the US chemical weapons stockpile. An approaching reality.

A congressional mandate to dispose of the current US stockpile of lethal unitary weapons (Public Law 99-145, Department of Defense Authorization Act of 1986) has international implications and is responsible for a recent major assessment of available disposal alternatives. Eight installations in the continental United States currently host aging stockpiles of chemical warfare agents. The stockpiles are described, the toxicology and physical properties of each agent are characterized, disposal options considered by the US Army are identified, and the role of a programmatic health and environmental assessment in the decision-making process is outlined. Critical findings are that existing community emergency planning and preparedness are inadequate and that communication of risk information requires significant improvement. Measures are under way to address these needs. However, timely disposal of the stockpile entails less of a hazard than continued storage.

Chemical Warfare Agents↗
PubMed1989

Sulfur mustard as a carcinogen: application of relative potency analysis to the chemical warfare agents H, HD, and HT.

A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 X 10(-4) mg HD/m3 and the occupational exposure level of 3 X 10(-3) mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 X 10(-8) and 1 X 10(-7). Lifetime cancer risk estimates less than or equal to 10(-6) are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10(-5) for the general public and 10(-4) for the worker population. These values are considered upper limit estimates.

Animals↗
PubMed1989

Plasma concentrations of catecholamines following intraocular irrigation with adrenaline.

Plasma concentrations of adrenaline and noradrenaline were measured in 13 patients undergoing cataract surgery after intraocular irrigation with an adrenaline-containing solution. Venous blood samples were withdrawn before, during and after intraocular irrigation with a solution of adrenaline 1:500,000. Plasma concentrations of both adrenaline and noradrenaline did not differ significantly from those noted before induction of anaesthesia.

Absorption↗
PubMed1988

Arborescent bacterial keratopathy (infectious crystalline keratopathy).

Bacterial colonisation of the cornea is described in two cases, one bilateral. Discreet, white, branching opacities are produced without associated inflammation. It is suggested that due to its aetiology "arborescent bacterial keratopathy" is a better name for this condition than "infectious crystalline keratopathy".

Administration, Topical↗
PubMed1988

Chemical scoring by a rapid screening of hazard (RASH) method.

A rapid screening of hazard method (RASH) is presented for deriving relative potency estimates for hazardous substances. The method utilizes data from any available toxicological database such as the Registry of Toxic Effects of Chemical Substances (RTECS) or EPA's GENE-TOX database on genetic activity profiles. The method has been applied to derive relative potency values and permissible environmental concentrations for 278 chemicals. The derived values have been compared with recommendations of expert committees where possible, and substantial agreement is found.

Animals↗
PubMed1987

Endothelial cell loss due to repeated traumatic wound dehiscence after penetrating keratoplasty.

A patient with keratoconus suffered two traumatic ruptures of her corneal graft wound, both of which were successfully repaired with restoration of graft clarity. There were also two apparently unrelated episodes of rejection. The endothelium was monitored by specular microscopy during this period. Our findings suggest that the insult to a transplanted cornea from an episode of rejection may be greater than that from traumatic wound rupture.

Adult↗
PubMed1987

Sudden-onset squint.

Differentiating a sudden-onset concomitant squint from a paralytic squint in an ill child can be difficult, but the distinction is important in view of the neurological implications of the latter. Furthermore, the two types may co-exist, and four such cases are described. The causes of sudden-onset squint are discussed. Methods of examination are described which may help to distinguish a paretic squint, with its neurological implications, from a concomitant deviation with no such systemic associations.

Abducens Nerve↗