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Pica and elevated blood lead level in autistic and atypical children.

Children with severely atypical development often display pica, habitual mouthing, and odd food preferences as symptoms from the first year of life. Such children can ingest dangerous amounts of lead even in environments that are usually considered safe. Mean blood lead concentration was notably higher in 18 autistic children than in 16 nonautistic psychotic children or in ten normal siblings. Fifteen (44%) of the psychotic children (autistic and nonautistic) had blood lead levels greater than two standard deviations above the mean for normal controls. Behavioral and neurological sequelae of elevated blood lead level may be obscured in severely disorganized children. Screening for blood lead should be part of the medical care of these vulnerable children with pica.

Adolescent↗

Fatal pneumococcal sepsis following flexible bronchoscopy in an immunocompromised infant.

A 5-month-old boy who suffered from a leukocyte chemotactic defect underwent flexible bronchoscopy for persistent right upper lobe atelectasis and tachypnea. Ten hours after the procedure he developed fulminant sepsis, and he died 16 hrs after bronchoscopy. Streptococcus pneumoniae (serotype 23) grew from the bronchoalveolar lavage fluid and from the blood culture taken during the sepsis work-up. We, therefore, suggest administering prophylactic antimicrobial therapy immediately following bronchoscopy to immunosuppressed children, even when an acute respiratory infection is not suspected, in order to prevent bacteremia and sepsis.

Bronchoscopy↗

Rat chromosome 9 bears a major susceptibility locus for IgE response.

Injection of Brown Norway (BN) rats with gold salts provides a model to analyze the genetic control of the IgE response. A cohort of F2 progeny of susceptible BN and resistant LEW strains has been studied to carry out a genome-wide search for loci controlling the IgE response. Genome scanning identified two previously described loci, Atps1 and Atps2, and a new locus, Atps3. Atps1 linked to the MHC and Atps2 linked to the cytokine gene cluster that included the IL-4 region have been previously associated with serum IgE concentrations and with other Th2-dependent immune manifestations triggered by gold salts. The new interval, Atps3, identified on chromosome 9 (Lod score = 16), appears to play a major role in the control of the IgE response since it accounts for 31% of the genetic variance. Moreover, Atps3 is linked to anti-laminin antibody response and to glomerular immunoglobulin deposits. The identification and functional characterization of genes involved in these regions, particularly in Atps3, may shed light on the pathogenesis of atopic diseases in man.

Animals↗

Effect of the thiol group on experimental gold-induced autoimmunity.

Brown Norway rats injected with aurothiopropanolsulfonate sodium salt develop systemic autoimmunity. The aim of this study was to assess the influence of the sulfur-containing group in this experimental model of gold-induced autoimmunity. It was shown that the sulfur-containing group does not induce autoimmunity of itself, but potentiates the immunotoxic effects of gold.

Animals↗

Pharmacokinetics of 14C-DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) in beagle dogs.

The pharmacokinetics of labelled DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) have been studied in four beagle dogs following bolus intravenous injection (65.7 mumol kg-1) and oral administration (197 mumol kg-1). Following intravenous injection the main kinetic parameters were t 1/2 = 43 min, V beta = 160 ml kg-1, and plasma clearance Clp = 2.6 ml min-1 kg-1. Following oral administration 14C-DMPS is rapidly absorbed with peak concentrations (478 +/- 25 mumol l-1) measured after 30-45 min. About 60 per cent of the oral dose was absorbed. Estimates of t 1/2, V beta, and Clp after oral administration were in close agreement with the values obtained in the intravenous study. 14C-DMPS is eliminated from the body by the kidneys. About 70 per cent of 14C-DMPS in dog plasma are bound to proteins. Binding is even higher in plasma from rat and man.

Administration, Oral↗

Rat anti-glomerular basement membrane antibodies in toxin-induced autoimmunity and in chronic graft-vs.-host reaction share recurrent idiotypes.

Cross-reactive idiotypes (CRId) borne on autoanti-glomerular basement membrane antibodies of Brown-Norway (BN) rats with mercury-induced glomerulonephritis have been described in the preceding study (Guéry, J.-C. et al., Eur. J. Immunol. 1990. 20:93). BN rats treated with sodium aurothiopropanol sulfonate or D-penicillamine, as well as (LEW X BN)F1 hybrids transferred with BN rat spleen cells, developed quite similar autoimmune abnormalities. In the present study, it is shown that immunoglobulins bearing such "public" idiotypes are also produced and deposited in the kidney in these three models. The CRId here described may, therefore, be considered as a marker of sets of recurrently expressed V region genes during the course of these autoimmune disorders. Anti-self class II T cells are present in the three models of toxin-induced autoimmunity and anti-allo class II T cells are responsible for the chronic graft-vs.-host reaction. The same B cell clones are probably triggered during these processes as a consequence of a polyclonal B cell activation mediated by anti-class II T cells.

Animals↗

A methylmercury toxicity model to test for possible adverse effects resulting from chelating agent therapy.

A daily dosing model for methylmercury (MM) intoxication was developed for the purpose of testing for possible adverse effects resulting from the administration of complexing agents used in the treatment of MM poisoning. The dithiol complexing agents 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) were chosen to test the discriminative ability of this model, since the former is contraindicated for MM poisoning and causes an increase in target organ MM burden, while the latter compound is known to be efficacious in reducing both toxicity and brain MM content. The basic design of the model called for daily observation of treated animals with identification of the following signs of MM intoxication: loss of body weight, onset of signs of toxicity, and mortality. The degree of toxicity was evaluated, and a toxicity score (0-5) was provided for each animal. A dose-dependent decrease in body weight was found in MM-treated mice. The latent period for development of signs of intoxication varied inversely with the dose rate. The rate of progression of severity of signs of intoxication was also dependent upon the dose. A dose rate of 14 mg Hg per kg per day was utilized to test the effects of BAL and DMSA on the onset and progression of signs of MM intoxication. Onset and progression of signs of methylmercury intoxication were similar for animals receiving methylmercury either alone or with administration of BAL at 2 mg per kg per day. Animals which received BAL at a dose rate of 20 mg per kg per day developed signs of intoxication significantly earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of three antidotes on arsenic toxicity in the common earthworm (Lumbricus terrestris).

The common earthworm (Lumbricus terrestris) is being evaluated in our laboratories as a substitute for mice in metal toxicity studies. These two disparate species have enzymes in common, such as catalase, superoxide dismutase and glutathione-S-transferase. Also, worms respond similarly to these rodents for selenium and nickel toxicity. Worms are less sensitive, however, to metal toxicity. In this study earthworms were challenged with three different arsenic compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The median lethal dose for each arsenic compound was determined. The order of toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24 h LD50 values were 189.5, 191.0 and 519.4 mumol kg-1, respectively). Individual mammalian dithiol antidotes, namely the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA) or 2,3-dimercapto-1-propanol (BAL), were injected into the worms 5 min after various doses of the arsenic compound were administered. The decreases in acute toxicity values were recorded. All three antidotes protected the worms against arsenic toxicity with varying degrees of effectiveness. The protective action for the inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic arsenical, PDA, the most effective antidote was BAL.

Animals↗