Excessive water drinking behavior in autism.

The aim of this study was to determine the incidence of polydipsia in 49 autistic children, and also the influence of psychotropic drugs and residential factors on water drinking behavior, as compared with in 89 mentally retarded children, in schools for mentally handicapped children in Fukui prefecture. Questionnaires were used to detect polydipsia and to assess the severity of the water drinking behavior in the autistic children and mentally retarded children. The incidence of polydipsia in the autistic children tended to be higher (P = 0.074) than that in the retarded children. The severity of water drinking behavior was significantly higher in autism (P = 0.022) than in mental retardation. The majority of the autistic children with polydipsia had been taking no psychotropic drugs. The incidence of polydipsia showed no significant difference between two residential situations, i.e. 'not at home' and 'at home'. The present study suggests that polydipsia or excessive water drinking behavior occurs more often in autism than in mental retardation, possibly due to some intrinsic factor in autism itself.

Ataxia-telangiectasia in the Japanese population: identification of R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being relatively common mutations.

We analyzed the data regarding six Japanese ataxia-telangiectasia (A-T) patients from four unrelated families, at the DNA level, to search for possible common mutations in the Japanese population. Among eight mutant alleles in the four families, c. 4612del165 (exon 33 skipping) was identified in two alleles, and c. 5749A to T (R1917X), c. 7471T to C (W2491R), c.7883de15, and c. 8725A to G (R2909G) were identified in one allele each. We found no mutations in the other two alleles. The IVS33 + 2T-->A mutation was identified at the genomic level as the cause of exon 33 skipping. We also identified the IVS33 + 2T-->A mutation in a Japanese patient ATL105 who was previously found to be a homozygote of c. 4612del165. W2491R and R2909G mutations were not detected in more than 100 control Japanese alleles. The latter is located in a highly conserved PI-3 kinase domain and is a completely conserved residue among ATM-related proteins. Taken together with previously documented mutations in five other Japanese A-T patients, IVS33 + 2T-->A and 7883del5 were identified in four and five alleles, respectively, in a total of 18 mutant alleles of Japanese A-T patients. These results suggest that these two mutations are relatively common mutations in the Japanese population.

[Two cases of infantile autism with intermittent water intoxication due to compulsive water drinking and episodic release of antidiuretic hormone (SIADH)].

The syndrome of water intoxication, resulting from dilutional hyponatremia and characterized by lethalgy, confusion, seizures, and coma was seen in two autistic boys living in the institution for mentally retarded children. Patient 1, a 19 year-old autistic boy showed loss of attention, inactiveness, sleepiness and delirium and then followed by overbreathing, severe vomiting and finally convulsive seizures several times, or coma, since October 1985. In August 1988, he was admitted with generalized tonic clonic convulsion associated with frequent vomiting EEG showed diffuse spike and wave complex with slow background activity. Laboratory data showed inappropriately high serum ADH level (8.5 pg/ml), low sodium concentration (121 mOsm/m/l), serum osmolality (237 mOsm/l) which was lower than urine osmolality (334 mOsm/l), and remarkable body weight gain (8.5 kg). He was diagnosed as water intoxication due to compulsive water drinking and SIADH. Diminished GH secretion to insulin-induced hypoglycemia and exaggerated prolactin response to LHRH stimulation suggested a hypothalamic lesion. Patient 2, a 17-year-old autistic boy, showed essentially the same symptoms and laboratory data as Patient 1, except that he had no epileptic discharge in EEG, and curious GH response to insulin-induced hypoglycemia. A remarkable daily body weight change suggested excessive water drinking and a possible episodic release of ADH. With mild water restriction, this became smaller. Since Patient 1 had epileptic attacks several times without hyponatremia and his EEG showed epileptic discharges, he was diagnosed as having epilepsy. Patient 2 has been seizure-free until now. Abnormality of hypothalamic or pituitary defects and polydipsia and possibility of water intoxication should always be considered when an autistic patients shows recurrent epileptic attacks or episodic strange behaviors with hyponatremia.

The prevalence of Rett syndrome in Fukui prefecture.

The present study was performed to estimate the prevalence of Rett syndrome in Fukui prefecture by sending questionnaires to special classes (classes for handicapped children in schools for normal children) and schools for mentally/physically handicapped children, and observing children suspected of having this syndrome on the basis of answers to the questionnaire. The subjects were girls aged 6-14 years who were attending 11 special classes and 7 schools for handicapped children. The prevalence of Rett syndrome was estimated to be 0.22 per 10,000 girls aged 6-14 years in Fukui prefecture, as of April 1, 1993. The prevalence noted in this study was lower than those found in previous studies in Japan and Western countries.

Long-term cultured mouse mast cells: ultrastructure, histamine and leukotriene levels.

Interleukin 3 (IL3), dependent cells were obtained from bone marrow (9/10 experiments) and spleen cells (4/5 experiments), but not from the thymus. These cells were similar to mucosal mast cell toluidine blue staining and electron microscopy. They had heterogenous metachromatic granules, and some had large scroll-like structures. They also contained histamine (200-800 ng/10(6) cells) for the first 2-5 weeks, whose level diminished to less than 30 ng/10(6) cells by 10 weeks of culture. They also generated leukotriene (LT) C4/D4 (10-40 ng/10(6) cells) and LTB4 (2-5 ng/10(6) cells) for over 100 days of culture. In one experiment, bone marrow-derived mast cells after 150 days of culture began to produce an IL3-like substance and proliferated exponentially without exogenous IL3.

Two cases of cystic fibrosis in Japanese children: studies on the essential fatty acid and prostaglandin metabolism.

We describe the fatty acid (FA) and prostaglandin (PG) metabolism in two Japanese cases of cystic fibrosis (CF) with or without pancreatic insufficiency (PI). The diagnosis of CF was based on the elevated sweat chloride concentration by pilocarpine iontophoresis. A 1-month-old boy (case 1) showed poor weight gain, steatorrhea and scaly dermatitis, but no respiratory symptoms were noted. He had decreased levels of serum linoleate and arachidonate, and increased palmitoleate and oleate levels, indicating essential fatty acid (EFA) deficiency. Supplementation of fat-emulsion improved his skin lesions and the altered FA pattern within a few months, associated with the definite reduction of the urinary PG F2 alpha levels. Until two years of age, he has been free from respiratory symptoms. A 12-year-old girl (case 2) had had recurrent respiratory tract infections due to Pseudomonas aeruginosa and Staphylococcus aureus for several years, and her pancreatic functions were preserved. The FA patterns of her serum lipid were almost within the normal range. These results indicate that 1) the altered FA composition appeared to be a secondary consequence of PI commonly complicating CF and 2) the correction of the altered FA and PG metabolism might have a beneficial effect on the respiratory function of CF patients with EFA deficiency.

Effect of adenosine and pertussis vaccine on lymphocyte response in vitro to phytohemagglutinin in asthmatic and non-asthmatic subjects.

Adenosine and pertussis vaccine each significantly suppressed the in vitro lymphocyte response to phytohemagglutinin (PHA) in both asthmatic and non-asthmatic subjects. On the other hand, pertussis vaccine significantly enhanced the response of the lymphocytes treated with a lower concentration of adenosine both in asthmatic and non-asthmatic subjects. It was also shown that lymphocytes from asthmatic and non-asthmatic subjects responded similarly to the modulating effect of adenosine and/or pertussis vaccine on PHA stimulation. These data give further evidence for the complex interplay of the vaccine with endogenous adenosine.

Increased serum IgE antibodies in institutionalized asthmatic children after a transient return home. The role of house dust mite allergens in the home as a trigger of asthmatic attacks in mite-sensitive patients.

Increased serum IgE antibodies to Dermatophagoides pteronyssinus, a house dust mite, were observed in 12 of 13 institutionalized mite-sensitive asthmatic children after returning for four days to their own homes. These results implicate the house dust mite as a trigger of asthmatic attacks in these patients.

Effect of sustained-release theophylline administration on pituitary-thyroid axis.

The effect of therapeutic doses of theophylline on the pituitary-thyroid axis was studied in four normal adults and in 15 asthmatic children on theophylline treatment. In the four normal adults, sustained-release theophylline was administered every 12 hr for 60 hr, and serial determinations of serum theophylline, thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyrotropin (TSH), and cyclic AMP (cAMP) were done. In all four cases, serum T4 increased significantly (134% +/- 4% vs basal level) with significant correlation to plasma cAMP level (r = 0.67, p less than 0.05). Changes in T3 and rT3 showed a marked individuality; an increase in T3 occurred in a subject with severe side effects, while the increase in rT3 was observed in a subject with mild side effects. Of the 15 children on theophylline treatment, a higher T4 level was found in 12 and a lower T3 level in nine at 1 wk, but these values returned to the previous level after 4 wk. These results indicate that the therapeutic doses of theophylline significantly but transiently increased the serum T4 level. In most cases, T4 is metabolized to rT3, an inactive metabolite of T4, but in a few cases it is metabolized to T3, which might double the side effects of theophylline.

Lymphocyte responsiveness to Dermatophagoides farinae extract in mite-sensitive patients: effect of immunotherapy on cellular proliferative response and specific immunoglobulin E antibody (RAST score).

Lymphocyte responsiveness in vitro and serum levels of specific IgE antibody to mite extracts (Dermatophagoides farinae) were evaluated in mite-sensitive asthmatic patients and in nonatopic individuals. Lymphocytes from untreated mite-sensitive patients (n = 16) responded to mite extracts with greater 3H-thymidine uptake than those from nonatopic individuals (n = 20; p less than 0.01). Specific IgE antibody and total IgE levels were significantly higher in mite-sensitive patients than those in nonatopic individuals. These results suggest that mite-sensitive patients respond to mite allergen with exaggerated lymphocyte proliferation as well as with enhanced specific IgE antibody production. Lymphocyte response to mite extracts was significantly lower in the patients with long-term dust immunotherapy than that in the untreated patients (p less than 0.05), but there was no significant difference in the total IgE and the specific IgE antibody levels between them. Lymphocyte response to Candida albicans was not significantly affected in these patients. These results suggest that as far as mite allergy is concerned, there is some difference in the effect of immunotherapy between lymphocyte proliferative response and specific IgE antibody to mite allergen.