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.     

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.     

Monitoring pressure ulcer healing in persons with disabilities.

Pressure ulcers are a high-risk, high-volume, and high-cost problem for persons with disabilities. This article describes four tools published in the literature and reports the validity, reliability, strengths, and limitations of each. These tools include the Pressure Ulcer Scale for Healing (PUSH), the Pressure Sore Status Tool (PSST), the Sussman Wound Healing Tool (SWHT), and the Sessing Scale. Rehabilitation nurses should use a consistent framework with accurate quantification to assess, document, and monitor changes in pressure ulcers over time. Such a measurement tool must prove valid for the disabled population in which the tool is used. This will enable healthcare providers to communicate more effectively and evaluate the therapeutic plan of care.     

Comparison of yogurt, soybean, casein, and amino acid–based diets in children with persistent diarrhea

Although previous studies have shown successful treatment of persistent diarrhea (PD) with the use of yogurt-based diets, some recent ones speculate the need of special formulas for the nutritional management of PD complicated cases. In the present study, we tested the hypothesis that the consumption of 3 lactose-free diets, with different degrees of complexity, is associated with lower stool output and shorter duration of diarrhea when compared with the use of a yogurt-based one on the nutritional management of PD. A total of 154 male infants, aged between 1 and 30 months, with PD and with or without dehydration, were randomly assigned to 1 of 4 treatment groups. Throughout the study, the patients were placed in a metabolic unit; their body weights and intakes of oral rehydration solution, water, and formula diets, in addition to outputs of stool, urine, and vomit, were measured and recorded at 24-hour intervals. Four different diets were used in this study: diet 1, yogurt-based formula; diet 2, soy-based formula; diet 3, hydrolyzed protein-based formula; and diet 4, amino acid–based formula. Throughout the study, only these formula diets were fed to the children. The data showed that children fed the yogurt-based diet (diet 1) or the amino acid–based diet (diet 4) had a significant reduction in stool output and in the duration of diarrhea. The use of an inexpensive and worldwide-available yogurt-based diet is recommended as the first choice for the nutritional management of mild to moderate PD. For the few complicated PD cases, when available, a more complex amino acid–based diet should be reserved for the nutritional management of these unresponsive and severe presentations. Soy-based or casein-based diets do not offer any specific advantage or benefits and do not seem to have a place in the management of PD.     

A Spanish version of the Family Assessment Device

Introduction  

This paper presents the results of a study on the psychometric properties of an authorized Spanish version of the McMaster Family Assessment Device, a self-report measure of family functioning.     

Nucleolin protein expression in cutaneous melanocytic lesions

Background:  Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.
Methods:  We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results:  Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion:  An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma.     

Reproducibility of food atopy patch tests over time in the general child population

Background  The atopy patch test (APT) is no longer an experimental method; it is increasingly being used as a standard diagnostic tool for the characterization of patients with aeroallergen- and food-triggered disorders. Some technical aspects of this test still remain to be answered. We aimed to study the reproducibility of this test over time in the general child population.
Methods  In a general population of 118 children, we investigated the reproducibility of duplicate APTs with four food allergens in their native form, which were repeated at set intervals from the first test: 7 days (group 1), 14 days (group 2), and 21 days (group 3).
Results  We observed very poor reproducibility on both sides of the back in all three studied subgroups. The reproducibility rates and Cohen's κ values did not improve when we did not consider the side of the back. There were no differences in the prevalence of atopy between the subjects with reproducible and nonreproducible APT results. All three groups studied showed no difference in the prevalence rates of atopy. There was no relationship between APT and skin prick test positivity for the same allergen. Questionnaire-derived data about previous food-related reactions did not help in the evaluation of the doubtful nonreproducible APT results with food allergens.
Conclusions  Our results show that the reproducibility of food APTs is poor and unsatisfactory over time, and there is an urgent need for the development of optimal, stable, and good-quality APT testing substances.     

Scabies

Scabies is an ectoparasite caused by the mite Sarcoptes scabiei var hominis , an obligate human parasite. There are about 300 million cases of scabies in the world each year. Common predisposing factors are overcrowding, immigration, poor hygiene, poor nutritional status, homelessness, dementia, and sexual contact. Direct skin-to-skin contact between 15 and 20 minutes is needed to transfer the mites from one person to another. The diagnosis suspected with a clinical history of itch, worse at night, affecting other family members, clinical distribution, and appearance. Definite diagnosis relies on microscopic identification of the mites, eggs, or fecal pellets with 10% potassium hydroxide, ink enhancement, tetracycline fluorescence tests, or mineral oil; other methods include: epiluminescence light microscopy and S. scabiei DNA. The most commonly used treatment modalities are permethrin and ivermectin. Persistence of symptoms for 2–6 weeks after successful treatment is common. Most recurrences are because of reinfection from untreated contacts.