Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors.

We investigated prospectively the incidence of autistic disorder (AD) in the neonatal intensive care unit and the risk factors associated with autistic development. The study population included the 5,271 children at St. Mary's Hospital and the diagnosis of AD was performed using DSM-III-R criteria. A total of 36 prenatal, perinatal, and postnatal factors were evaluated in the patients with AD, 57 cerebral palsy (CP), and 214 controls. AD was identified in 18 of the 5,271 children and the incidence was 34 per 10,000 (0.34%). This value was more than twice the highest prevalence value previously reported in Japan. Children with AD had a significantly higher history of the meconium aspiration syndrome (p = .0010) than the controls. Autistic patients had different risk factors than CP.

Helicobacter pylori seropositivity in patients with severe neurologic impairment.

The objective of this study was to assess the prevalence of Helicobacter pylori seropositivity in institutionalized patients with severe neurologic impairment. Anti-H. pylori immunoglobulin G antibody in serum was measured in 196 institutionalized Japanese patients using enzyme linked immunosorbent assay, taking an antibody level >50 units/ml as evidence of H. pylori seropositivity. Patient age pattern and duration of institutionalization were examined for the relationships with H. pylori seropositivity. We also examined for seroconversion indicating new H. pylori infection in initially negative patients 1 year later. Positivity for H pylori infection among institutionalized patients was also compared with positivity among patients living at home. H. pylori seropositivity was present in 81.1% of subjects. Prevalence of H. pylori seropositivity increased with both age and duration of institutionalization. The serum level of anti-H. pylori immunoglobulin G antibody in patients over 20 years old was consistently high, approximately twice that of subjects less than 10 years of age. Of 38 patients initially negative for H. pylori infection, 18 (47.4%) had become positive at 1 year. H. pylori seropositivity was significantly more prevalent among institutionalized patients than among patients living at home (P < 0.0001). This study confirms that high H. pylori seropositivity rates are found among institutionalized patients with severe neurologic impairment. Our observations suggest person to person transmission, with fecal to oral, salivary secretion and respiratory droplet routes possibly being important pathways.

Early intervention for very-low-birth-weight infants.

To assess the efficacy of early intervention (EI) for very-low-birth-weight (VLBW) infants, we evaluated 62 2 year old children who were enrolled in an EI program and 48 control subjects aged 2 years. We determined the subjects' developmental quotients (DQ) and obtained information about the parents' evaluation of the children from a questionnaire sent to the parents. There was no significant difference in the DQ between the EI group and the control group. However, based on the responses to the questionnaire, subjects in the EI group showed slight, but statistically marginally significant, improvements in behavioral problems, especially a decrease in hyperkinesia, in adjusting to a circadian sleep cycle, and an improvement in language development, as compared with the control group (P < 0.1). Thus, EI for VLBW infants is considered useful to enhance some areas of development.

Significance of the preoperative intravesical instillation of doxorubicin and the oral administration of 5-fluorouracil in preventing recurrence after a transurethral resection of superficial bladder cancer. Kyushu University Urological Oncology Group.

BACKGROUND: The postoperative intravesical instillation of doxorubicin (ADM) has a preventative effect on recurrence after a transurethral resection (TUR) of superficial bladder cancer. However, the significance of preoperative ADM instillation remains unclear. Although the oral administration of 5-fluorouracil (5-FU) has been observed to show some clinical response against bladder cancer, its preventative effect on the recurrence of superficial bladder cancer after TUR is unknown. METHODS: Patients were randomized into 4 groups. All 4 groups received postoperative ADM instillation. In addition, patients in groups C and D received preoperative ADM instillation, whereas patients in groups B and D additionally received oral 5-FU postoperatively. The nonrecurrence rate and side effects were both compared among the 4 groups. RESULTS: Of the 282 patients registered, 200 were evaluable, with a median follow-up period of 21.4 months. There were no significant differences in the characteristics of the patients among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly longer disease-free interval than group A (postoperative ADM alone). However, there was no significant difference in the disease-free interval between groups A and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and postoperative ADM plus 5-FU). Bladder irritation symptoms were the most frequently noted side effect encountered in all groups, but the severity was generally mild. CONCLUSIONS: Preoperative ADM instillation was found to prevent recurrence to a greater extent than the usual postoperative instillation alone, whereas oral 5-FU was found to have no additional beneficial effect on the disease-free interval in patients with superficial bladder cancer.

Dexamethasone and bacterial meningitis in Pakistan.

The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.

Intellectual development of offspring of diabetic mothers.

We prospectively evaluated the intellectual development of 33 children who were born to 33 diabetic Japanese mothers and compared them to 34 children born to non-diabetic mothers (controls) during the same period at Kurume University Hospital between 1987 and 1989. Birthweight, maternal age and the infant's age at the time of intelligence testing did not differ significantly between the offspring of diabetic mothers (ODMs) and controls. Tanaka-Binet intelligence scores were significantly lower in the ODMs at 3 years of age than in controls (98.4 +/- 17.4 versus 113.4 +/- 15.3) (p = 0.0005). No correlation was found between IQ and maternal haemoglobin A1c levels during pregnancy. Maternal age and infant IQ were inversely correlated in ODMs (p = 0.0298, r = -0.3984), but no such correlation was demonstrated in the controls. The results indicated that the ODMs may show a poorer intellectual development than those of non-diabetic mothers.

[Early intervention for very-low-birth-weight infant].

In order to establish an early intervention (EI) system for very-low-birth-weight infants, we designed a randomized trial at multiple institutions in Japan. We also reviewed the concept and history of early intervention in USA. Eight medical institutions in different locations were selected for participation. Sixty-two EI group patients and 48 controls without neurological abnormalities (age 2 years) were selected for study. The developmental quotient (DQ) by the revised Kyoto-K method and 15 questionnaire items were monitored twice, at the age of 2 and after one year of EI (3 years). Improvements in behavioral problems, circadian rhythm, and speech were significantly greater in the EI group than in the control group. (P < 0.01). Data on all patients are being collected, and further evaluation and analysis of DQ are planned. The most effective EI method in each specific location and the financial support of its official institutions are required for the success of the EI program for very-low-birth-weight infants.

Immediate allergy to rubber gloves: a questionnaire study of hospital personnel.

We conducted a questionnaire study of immediate allergy to natural rubber gloves among 2,408 medical workers who had used rubber gloves at Kumamoto University Hospital and allied hospitals. The response rate was 64.5% (1,321 workers). Among them, 8.5% (7.0-10.0% at 95% confidence limit) replied that they had experienced immediate allergy to rubber gloves. There were significant correlations among the frequency of rubber glove use, a history of atopic dermatitis or contact dermatitis, and the presence of skin lesions due to allergic reactions to rubber gloves. In 27 workers, skin lesions were associated with general symptoms. Of 59 workers who experienced immediate allergy and were tested for latex-specific IgE, 4 persons were positive. We conclude that the frequency of contact allergy to natural rubber products is substantially prevalent among Japanese hospital personnel and that education and awareness of this allergy are important.

Fetal bile acid metabolism during infancy: analysis of 1 beta-hydroxylated bile acids in urine, meconium and feces.

Fetal bile acids (1 beta-hydroxylated, 6 alpha-hydroxylated and unsaturated bile acids), especially 1 beta, 3 alpha,7 alpha, 12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid (CA-1 beta-ol), have been detected in urine and feces early in life. To investigate whether a fetal pathway of bile acid synthesis exists in infancy, we measured the concentrations of bile acids in the urine, meconium and feces from normal newborns and infants by means of gas chromatography-mass spectrometry. The mean ratio of total bile acids to creatinine in urine increased between birth and 7 days and then gradually decreased; however, the concentration of total bile acids in urine remained significantly higher than that in adult urine until 3 mo of age. The main urinary bile acid was CA-1 beta-ol, and substantial amounts of fetal bile acids were detected in urine until 3 mo of age. The ratio of cholic acid to chenodeoxycholic acid was abnormally low in meconium (mean, 0.44; range, 0.19 to 0.74), and hyocholic acid constituted 19.3% of total bile acids. The mean total bile acid content of feces decreased between birth and 7 days of age and thereafter increased. The mean percentage of fetal bile acids in feces decreased after birth, but substantial amounts were present in feces until 1 mo of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal reference growth curves for very low birth weight infants.

To construct standard growth curves for Japanese infants of very low birth weight (VLBW) with birth weights of 500-1499 g, we reviewed longitudinal data provided by 54 neonatal intensive care units in Japan. A total of 382 surviving singleton infants, appropriate for gestational age infants, and who were free of neurological sequelae at more than 2.5 years of age, were enrolled. Growth curves, including body weight, head circumference and body length were generated for four ranges of birth weight: 500-749 g, 750-999 g, 1000-1249 g, and 1250-1499 g. When compared with previously published growth data from western countries, Japanese infants of VLBW showed greater weight loss, regained birth weight more slowly, and exhibited smaller average gains in weight, head circumference, and body length. The growth curves reported in western countries may not be useful as reference standards of early postnatal growth in Japan. The new growth curves are a more accurate reflection of current in-hospital growth trends in Japan.

Abnormal carbohydrate metabolism in cerebrospinal fluid in Rett syndrome.

We analyzed lactate, pyruvate, and citric acid cycle intermediates in cerebrospinal fluid by high-performance liquid chromatography in Rett syndrome patients (n = 27; mean age, 5.7 +/- 3.4 years) and age-matched female controls (n = 12; mean age, 7.0 +/- 3.3 years). The lactate, pyruvate, alpha-ketoglutarate, and malate were significantly elevated in Rett syndrome compared to the controls. The lactate/pyruvate ratio was not different. On the other hand, cerebrospinal fluid citrate, cis-aconitate, succinate, fumarate, and oxaloacetate were not significantly different in Rett syndrome patients than in the controls. We also evaluated the correlation between these acids and clinical symptoms and signs, including clinical stage, seizures medications (anticonvulsants or naltrexone), developmental quotient, self-abuse, and hyperventilation or apnea or both. The concentrations of all these acids did not differ significantly with clinical stage. Lactate elevation significantly correlated with apnea. Lactate and pyruvate elevation significantly correlated with hyperventilation or with both breathing abnormalities. Our observations in this sample of patients with Rett syndrome led us to speculate that patients with the Rett syndrome may have defective carbohydrate metabolism. Elevated mitochondrial reduced nicotinamide-adenine dinucleotide-linked substrates suggest that reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase may be deficient in the brain in Rett syndrome patients.

Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma.

Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.

Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis.

In a recent study we detected marked differences in the antigenic profile of acral lentiginous melanoma (ALM) and nodular melanoma lesions. Furthermore, we showed that the human high molecular weight melanoma-associated antigen (HMW-MAA) is expressed with a significantly higher frequency in metastatic than in primary ALM lesions. Because of the potential role of HMW-MAA in the metastatic process of melanoma cells, in the present investigation we tested whether HMW-MAA represents a useful prognostic marker in ALM. Primary ALM lesions removed from 32 patients were stained with anti-HMW-MAA monoclonal antibody (mAb) in an immunoperoxidase reaction. The results were correlated with the expression of other markers defined by mAb, with clinical parameters of the disease, and with histopathological characteristics of the lesions. Only 9 of the 32 primary ALM lesions tested were stained by anti-HMW-MAA mAb. Expression of HMW-MAA was the only variable associated with patients' survival and disease-free survival. Both were significantly shorter in patients with HMW-MAA expression in their primary lesions. These results suggest that HMW-MAA may represent a novel prognostic marker in ALM, since phenotyping of primary ALM lesions with anti-HMW-MAA mAb may provide information about the prognosis of the disease which cannot be obtained with known prognostic parameters.

Postnatal growth curves of very low birthweight Japanese infants.

To construct standard growth curves for Japanese infants of very low birthweight, longitudinal data provided by 47 neonatal centers in Japan were reviewed. Data were collected on the growth of infants admitted to those units during 1986 and 1987 and who survived beyond 3 years of age. A total of 379 singleton infants, who were free of neurological sequelae and appropriate for gestational age, were enrolled. Those whose birthweights were more than 600 g and less than 1,500 g were grouped into nine weight categories separated by increments of 100 g. Data on the increase in weight and head circumference were compiled and analyzed until more than half the infants in each weight category had been discharged from each site. Growth curves of bodyweight and head circumference in the nine groups were constructed using polynomial regression analysis to define the curve of best fit. With increasing prematurity, significant trends of greater weight loss (P < 0.05), longer time to reach the lowest weight (P < 0.01) and a longer time to regain birthweight (P < 0.01) were observed. In addition, there was a significantly higher incidence of chronic lung disease in such groups (P < 0.0001). Growth curves were characterized by the average clinical profiles in each of the nine groups. We believe that these data will be useful in evaluating the growth of very low birthweight infants being cared for in modern neonatal intensive care units in Japan.