Poisoning due to Pyrethroids

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give α-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the α-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium ‘tail current’) ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and ‘conduction block’ ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4–8 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12–24 hours, specific treatment is not generally required, although topical application of dl-α tocopherol acetate (vitamin E) may reduce their severity.     

A comparison of Nd:YAG laser damage thresholds for PMMA and silicone intraocular lenses

Power density producing damage at a probability of 0.5 (ie, damage threshold, DT-50) was determined for PMMA (with/without UV absorber) and Silicone intraocular lenses. Scattered light from a collinear diagnostic He:Ne beam was one of four damage monitors deployed to enhance the sensitivity of the system. In order of increasing laser resistance the following results were obtained: injection molded PMMA (1.9/GW/cm2) Silicone (2.63 GW/cm2) Lathe-cut PMMA (4.47 GW/cm2), Lathe-cut PMMA with UV absorber (8.32 GW/cm2), Cast-molded PMMA (12.30 GW/cm2). An analysis of variance revealed interclass differences significant at the .01 level. Cast-molded PMMA was the most laser-resistant IOL material.     

Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused of isomers of benzanthracene

Many polycyclic aromatic hydrocarbons containing peripherallyfused cyclopenta rings are believed to be activated primarilyby epoxidation of the cyclopenta ring. The cyclopenta epoxidesof a series of four cyclopenta benzanthracene derivatives, benz[e]aceanthrylene-5,6-oxide,benz[j]ace-anthrylene-1,2-oxide, benz(l)anthrylene-1,2-oxideand benz[k]acephenaceanthrylene-4,5-oxide were synthesized fromtheir parent hydrocarbons by formation of the bromohydrin followedby dehydrobromination, and characterized by u.v. – vis,and ¹H n.m.r. spectroscopy and mass spectrometry. The mutagenicityof these compounds was investigated in the Ames plate incorporationassay with Salmonella typhimurium strain TA98. All the oxideswere active without exogenous metabolic activation (170–320His⁺ revertants per nanomole) and also toxic above 0.5 µg/plate.Addition of S9 protein did not increase, and generally decreased,the mutagenicity of the oxides, while toxicity was largely unchanged.These results are consistent with the postulated role of cyclopentaoxides as major contributors to the mutagenicity of the parentcompounds in the Ames assay.     

Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain.

Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.     

Nonabsorbable marker and single, random stool samples used for measuring intestinal absorption of macronutrients in infants and children

To measure intestinal absorption by using a single, random stool sample, polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration, apparent intestinal absorption of macronutrients was estimated from a standard 3-d metabolic balance and compared with that estimated by using the ratio of PEG to macronutrients in a single random sample of feces. Correlation coefficients for this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat, respectively. Additionally, apparent intestinal absorptions estimated from two separate consecutive 3-d metabolic-balance studies were compared, showing correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate, and fat, respectively. The random sample-marker technique appears to be acceptable for measuring apparent absorption of macronutrients and is at least as accurate as a standard 3-d metabolic-balance study.     

Relative effects of diarrhea, fever, and dietary energy intake on weight gain in rural Bangladeshi children

Quantitative studies of morbidity, food intake, and somatic growth were done prospectively during 14 mo for 70 children aged 5-18 mo in two Bangladeshi villages. When random-effect regression models were used, monthly changes in weight were inversely related to proportions of days in the month with fever and diarrhea and positively related to energy intake per kilogram body weight. Interestingly, weight changes did not vary with age in this interval. Estimates indicate that increasing energy intakes to the recommended World Health Organization level would have a significantly greater effect on weight gain than would the elimination of diarrhea and fever. With energy at recommended intake and diarrhea and fever prevalence as found in US children, weight gain is predicted to be near that of the international reference population. Therefore, interventions aimed at improving dietary intake may be as important as infection-control programs for improving growth of children in poor developing nations.