Acute ill-health in sheep farmers following use of pesticides.

BACKGROUND: Sheep farmers often complain of acute ill-health, known colloquially as 'dipper's flu', immediately after treating sheep with pesticides. There have been few prospective epidemiological studies to determine it's nature and incidence. Aims To determine the nature and frequency of symptoms occurring in farmers treating sheep for ectoparasites. METHODS: In a longitudinal study, farmers who planned to treat their sheep for ectoparasites were recruited. Farmers kept a symptom diary for 7 days after starting pesticide treatment. Symptoms reported on days 1-6 were compared to those reported on day 7 via the McNemar's test and with previously published literature definitions of dipper's flu. A principal component analysis (PCA) was carried out on new symptoms occurring on days 1 and 2. RESULTS: Of 781 farmers recruited, 352 farmers (45%) completed the symptom diary. In the 7 days after starting pesticide treatment, symptom complex reporting typically peaked on day 2, but few farmers (7 or less; <2%) were identified as having dipper's flu using literature definitions. However, PCA identified two new patterns of symptom complexes that accounted for 35% of the variance. A pyrexial factor consisted of four symptom complexes (feeling generally ill; feeling sweaty, shivery, feverish, hot or cold; feeling unusually tired; and having a headache) and a respiratory factor consisted of three symptom complexes (runny, stuffy, blocked or irritated nose; cough, shortness of breath or wheeze; and eye irritation). CONCLUSIONS: Existing definitions of dipper's flu do not adequately describe symptoms that occur following the treatment of sheep for ectoparasites.

Long-term event-related potential changes following organophosphorus insecticide poisoning.

OBJECTIVE: To determine prolonged effects of organophosphorus (OP) insecticide poisoning on cognitive event-related potentials (ERPs). METHODS: ERPs of a group of 32 patients recovered from cholinergic phase of OP insecticide poisoning were compared with those of two matched control groups: 32 healthy volunteers and nine patients hospitalised with paracetamol overdose. A follow-up assessment was done in 21 patients (66% of the initial sample) 6 months after OP intoxication and the findings were compared with their initial ERP data. RESULTS: Patients showed highly significant prolongation of P300 latency, compared to healthy controls (p=0.003) and the controls with paracetamol overdose (p=0.016). Follow-up ERP findings of the patients revealed that this impairment remained unchanged even 6 months after OP poisoning (p=0.790). There was no significant difference in N100, P200 and N200 latencies or P300 amplitude either among the groups or between the two assessments of the patients with OP poisoning. CONCLUSIONS: Our results suggest that acute OP poisoning causes a delay in cognitive processes involved in stimulus classification, lasting at least for 6 months. SIGNIFICANCE: These findings highlight the possibility of development of long-lasting cognitive deficits following OP insecticide poisoning, and warrant longer-term prospective studies to determine whether this impairment is permanent.

Cognitive processing of visual stimuli in patients with organophosphate insecticide poisoning.

OBJECTIVE: To determine the effect of organophosphate (OP) insecticide poisoning on cognitive processing time of visual stimuli. METHODS: We compared 33 patients who recovered from the cholinergic phase (on average, 15 days after poisoning) with an age- and sex-matched control group. The tests used were simple visual reaction time (SVRT), recognition visual reaction time (RVRT), visual evoked potentials (VEP), and motor evoked potentials (MEP). The term cognitive processing time (CPT) was used to denote the time taken from the initial cortical perception of a stimulus to initiation of the descending motor impulse. CPT of each type of visual reaction was calculated by subtracting the sum of the visual impulse duration and the motor impulse duration from reaction time (CPT = reaction time-[P100 latency + total motor conduction time]). RESULTS: Both the SVRT and RVRT were significantly prolonged in patients. There was no significant difference in P100 latency or total motor conduction time (TMCT) between patients and the controls. However, CPT of simple visual reactions (CPT(SVR)) and the CPT of recognition visual reactions (CPT(RVR)) were significantly prolonged in patients. CONCLUSIONS: Acute organophosphate poisoning may slow higher-order cognitive processing involved in visual stimulus detection and visual stimulus discrimination, even after clinical recovery from the cholinergic phase.

Organophosphate toxicity and occupational exposure.

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.

Variables influencing the toxic response to organophosphates in humans.

Concerns and doubts associated with the predictable health effects in humans following exposure to xenobiotics is primarily due to the failure to consider the variables influencing the toxic response in each instance. Lack of correlation between laboratory data, animal experiments and clinical findings in man associated with exposure to organophosphates (OPs) is an example. We have reviewed the literature to identify the variables that need to be considered following exposure to OPs. These include factors related to the OP (physico-chemical properties, solvents, impurities), duration and routes of exposure, and factors related to the individual(s) exposed. Individual variables include variations in metabolic, sequestration and excretory processes and health status (age, gender, environmental factors, concurrent medications, cholinergic status). The assessment of ill-health following exposure is critical to the development and compliance with guidelines and to the adoption of the best instrumentation. We have suggested a schematic assessment that needs to be applied for each exposure associated with organophosphates and provided the reasons for the development of this format. Exposure to xenobiotics through the environment, occupation or following therapy is an unavoidable aspect of modern life. Application of the principles discussed to each xenobiotic exposure is necessary to provide accurate and adequate information to advance the prevention or minimising toxicity.

Possible immediate and long-term health effects following exposure to chemical warfare agents.

Agents of chemical warfare continue to pose a threat to human life. Organophosphorus compounds are possibly the best known and most used agents in recent times. These are known to produce acute ill health and death and, probably equally important, many diverse delayed effects, many of which are not clinically nor pathologically well defined. The immediate and delayed effects of organophosphorus compounds, in particular, and those of other known agents of chemical warfare, such as mustard gas, Lewisite, phosgene, cyanides and the newer crowd control agents, are reviewed. Environmental sequelae of these agents are gaining importance as probable causes of chronic ill health amongst those living in regions where these agents have been used. The need to study the pattern of disease in exposed populations is emphasised.

Organophosphorus poisoning and anaesthesia.

Organophosphorus compounds, used as insecticides and agents of chemical warfare, are a major global cause of health problems. These irreversible inhibitors of cholinesterase produce three well-recognised clinical entities: the initial cholinergic phase, which is a medical emergency often requiring management in an intensive care unit; the intermediate syndrome, during which prolonged ventilatory care is necessary; and delayed polyneuropathy. In addition, disturbances of body temperature and endocrine function, electrolyte imbalances, immunological dysfunction and disorders of reproduction have been reported in animals and man. Vocal cord paralysis, pancreatitis, cardiac arrhythmias and a wide range of neuropsychiatric disorders are known to follow acute and chronic exposure to organophosphorus compounds. As a result of the inhibition of plasma cholinesterase, there can be increased sensitivity to drugs hydrolysed by this enzyme, e.g. suxamethonium and mivacurium. The inhibition of acetylcholinesterase causes dysfunction at the neuromuscular junction which can produce altered responses to nondepolarizing neuromuscular blockers. Anaesthetists may encounter patients exposed to organophosphorus compounds either following acute poisoning, trauma (warfare) or as patients with a wide range of nonspecific disorders presenting for surgery. The traditional use of oximes and atropine in treatment has failed to reduce the morbidity and mortality associated with poisoning. The roles of agents that have reduced the toxicity of organophosphorus compounds in animal experiments are discussed as potential therapeutic agents. There is an urgent need for accurate information on the problems associated with exposure to organophosphorus compounds. This would best be achieved by collaborative research between technologically advanced countries and developing countries, where organophosphorus compounds are a leading cause of ill health.

Drug interactions and the clinical anaesthetist.

In clinical practice, anaesthetists encounter many patients who are on concurrent medication which may have the potential to interact with drugs used during anaesthesia. Many patients are receiving as many as a dozen drugs of various kinds, thus, increasing the risk of a drug interaction occurring. Unfortunately anaesthetists tend not to report drug interactions which occur during anaesthesia--especially those of a minor nature such as flushing--and hence, the true number of drug interactions is unknown. We have developed a chart indicating the nature of important interactions that the anaesthetist may encounter.

General anesthesia for disabled patients in dental practice.

We reviewed the cases of 91 consecutive patients with disabilities who required general anesthesia at a tertiary referral center for dental treatment with a view to determining the factors that create difficulties in the anesthetic management. The more important of these are the special difficulties involved in making preoperative assessments of these patients and the difficulty in establishing monitoring. Other difficulties in anesthesia for these patients involve problems with gaining intravenous access, problems in determining when there has been adequate recovery from anesthesia, and problems in determining the degree of discomfort or pain the patients experience after dental treatment. Another potential hazard in this group of patients is the risk of drug interactions. We emphasize the need to train anesthetists in the care of disabled patients.

Drug interactions with neuromuscular blockers.

Drugs administered to patients undergoing anaesthesia may complicate the use of the neuromuscular blockers that are given to provide good surgical conditions. The various sites of interaction include actions on motor nerve conduction and spinal reflexes, acetylcholine (ACh) synthesis, mobilisation and release, sensitivity of the motor end plate to ACh and the ease of propagation of the motor action potential. In addition, many drugs affect the pharmacokinetics of neuromuscular blockers, especially as most drugs depend to a greater or lesser extent upon renal excretion. The clinically significant interaction between nondepolarisers and depolarisers may be due to blockade of the pre-synaptic nicotinic receptors by the depolarisers, leading to decreased ACh mobilisation and release. Synergism between nondepolarisers probably results from post-synaptic receptor mechanisms. Volatile anaesthetic agents affect the sensitivity of the motor end-plate (post-synaptic receptor blockade) in addition to having effects on pre-synaptic nicotinic function. The effects of nondepolarisers are likely to be potentiated and their action prolonged by large doses of local anaesthetics due to depression of nerve conduction, depression of ACh formation, mobilisation and release, decreases in post-synaptic receptor channel opening times and reductions in muscular contraction. Most antibacterials have effects on pre-synaptic mechanisms. Procainamide and quinidine principally block nicotinic receptor channels. Magnesium has a marked inhibitory effect on ACh release. Calcium antagonists could theoretically interfere with neurotransmitter release and muscle contractility. Phenytoin and lithium decrease ACh release, whilst corticosteroids and furosemide (frusemide) tend to increase the release of the transmitter. Ecothiopate, tacrine, organophosphates, propanidid, metoclopramide and bambuterol depress cholinesterase activity and prolong the duration of the neuromuscular block. The probability of clinically significant interactions increases in patients receiving several drugs with possible effects on neuromuscular transmission and muscle contraction.

Unfinished business: adult immunization against tetanus.

Where effective child immunization schemes have been established virtually all cases of tetanus occur in persons aged over 50 years. Adult immunization programmes should be introduced in order to protect this age group against the disease.

Immunity to tetanus in United Kingdom populations.

As tetanus, a totally preventable disease, is still encountered in the older age group in England and Wales, a study was carried out to assess the state of immunity to the disease in the elderly population. These levels were compared to those in recruits and service personnel in the Army. Elderly patients with underlying disease had lower levels than the elderly who were healthy. When compared with recruit population the elderly group had significantly lower levels of antibody. If tetanus is to be eliminated, an effective programme of immunisation extending throughout life must be ensured.