Upadacitinib for moderate-to-severe atopic dermatitis: Stratified analysis from three randomized phase 3 trials by key baseline characteristics.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. OBJECTIVES: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD. METHODS: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. RESULTS: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. CONCLUSIONS: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up).

Acute pathophysiological responses in the normal lungs of newborn piglets exposed to pure oxygen.

AIM: We investigated the effect of short-term pure oxygen treatment on pulmonary function, serum cytokine levels, and apoptosis in the lungs of healthy newborn piglets. METHODS: Twelve newborn piglets were randomly assigned to receive pure oxygen (OXY) (N.=6) or room air (AIR: 21% oxygen) (N.=6) for 4 hours. Cardiopulmonary function serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF) α were evaluated. Histology was used to assess apoptosis and morphological differences between treatment groups. RESULTS: Four-hour treatment with 100% oxygen resulted in higher PaO2, AaDO2, and compliance of the respiratory system (Crs) in the OXY than in the AIR animals. Serum levels of IL-6 were significantly higher in OXY piglets compared with AIR piglets (P=0.009), but there were no differences between groups in the serum levels of IL-1ß and TNF-α (P=0.640 and P=0.306, respectively). The piglets in the OXY group had a greater average number of apoptotic cells in the lung than AIR piglets, although this did not reach statistical significance. CONCLUSION: Our findings indicate that treatment with 100% oxygen for 4 hours may have clinical benefit by improving pulmonary function in normal neonates with limited increases in the inflammation and apoptosis.

Identification and molecular characterization of two novel chromosomal deletions associated with autism.

Autism is a childhood-onset neurodevelopmental disorder with a strong genetic basis in its etiology. Conventional karyotype analysis has revealed that chromosomal structural aberrations such as translocation, inversion, deletion, and duplication play a role in causing autism spectrum disorders (ASD). In addition, recent array-based comparative genomic hybridization (array CGH) studies discovered that submicroscopic deletion and duplication of DNA segments also contributed significantly to the genetic etiology of ASD. Together, these studies indicate that genomic rearrangement is an important genetic mechanism of ASD. Using karyotyping analysis and array CGH technology, we identified a subtelomeric deletion of approximately 6.8 Mb at 4q35.1-35.2 and a terminal deletion of approximately 2.4 Mb at 8p23.2-pter in two autistic boys, respectively. These two deletions were further validated using fluorescent in situ hybridization and real-time quantitative polymerase chain reaction, and their breakpoints were delineated using high-resolution array CGH. The 4q deletion is a rare de novo mutation, while the transmission of 8p deletion is unknown, because the father of the patient was unavailable for study. These two deletions are rare mutations and were not found in the additional 282 patients with ASD and in the 300 control subjects in our population. The identification of these two chromosomal deletions contribute to our understanding of the genetic basis of ASD, and the haploinsufficiency of several genes located at the deleted regions of chromosome 8p and 4q may contribute to the clinical phenotypes of autism.

Influences of biological risk at birth and temperament on development at toddler and preschool ages.

PURPOSES: This study aimed at investigating: (1) the effects of temperament and biological risk at birth on various developmental domains at toddler and preschool ages; (2) the interaction effects of the biological risk and temperament on development. Participants One hundred and ten full-term and 98 preterm children without significant physical or developmental disabilities and consisting of various biological risks were examined at toddler age (18-36 months) and preschool age (51-67 months). METHODS: The Neonatal Medical Index was used to classify the biological risk level. Parental reports on the Chinese Toddler Temperament Scale at toddler age were collected and the temperament (easy, intermediate and difficult) of each child was assigned according to local norm. The Comprehensive Developmental Inventory for Infants and Toddlers was used for assessing child development at toddler and preschool ages. Other family variables were also collected as possible confounders for child development. Two-way ancova was conducted to analyse the predictability of biological risk and temperament, by controlling the potential family variables on child development. RESULTS: At toddler age, higher biological risk had significant adverse effects on both the Perceptual-motor developmental quotients (DQs) (F(1,201)= 19.4, P < 0.001) and Social-adaptive DQs (F(2,200)= 22.5, P < 0.001), while easy temperament had positive effects only on the Social-adaptive DQs (F(2,200)= 7.7, P < 0.01). At preschool age, none of the two factors had effects on DQs of the Comprehensive Developmental Inventory for Infants and Toddlers. There were no significant interactions between biological risk and temperament on DQs at both ages. CONCLUSION: The biological risk and temperament affected child development at toddler age but not at preschool age. No interaction of biological risk and temperament effects on the child development at toddler age existed. The effects of biological risk and temperament on child development were temporary for the children with relatively low biological risk.

A randomized clinical trial study on the effectiveness of a tele-analogy-based problem-solving programme for people with acquired brain injury (ABI).

PRIMARY OBJECTIVE: The present study reports the results of 103 persons with acquired brain injury who were randomly assigned to one of three 20-session analogy problem-solving skill training groups, namely: online training (through computer video conferencing with interactive software); computer-assisted training (through interactive patient-directed software); therapist administered training (face-to-face therapist guided training activities); and a "no-treatment" control group. RESEARCH DESIGN: Pre- and post-test quasi-experimental design. MAIN OUTCOME AND RESULTS: Individuals' problem-solving skills and self-efficacy in all four groups were assessed over a four-week period. Overall, the training methods were found to be effective in improving problem solving skills regardless of the modes of delivery (except in the case of the control group). The continuous "human touch" characteristics of the therapist-administered group showed significant better improvements in self-efficacy in problem-solving. CONCLUSION: The statistically significantly improvement in problem solving skills in the online-group suggests that this approach could effectively improve cognitive functions of person with ABI and yield training outcomes comparable to other modes of delivery such as the face-to-face training. The conceptualization and applicability of tele-cognitive rehabilitation, its implications for persons with ABI, and future studies in this research area are also discussed.

Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure of B-cell development that incapacitates antibody production in XLA patients leading to recurrent bacterial infections. Btk SH2 domain is essential for phospholipase C-gamma phosphorylation, and mutations in this domain were shown to cause XLA. Recently, the B-cell linker protein (BLNK) was found to interact with the SH2 domain of Btk, and this association is required for the activation of phospholipase C-gamma. However, the molecular basis for the interaction between the Btk SH2 domain and BLNK and the cause of XLA remain unclear. To understand the role of Btk in B-cell development, we have determined the stability and peptide binding affinity of the Btk SH2 domain. Our results indicate that both the structure and stability of Btk SH2 domain closely resemble with other SH2 domains, and it binds with phosphopeptides in the order pYEEI > pYDEP > pYMEM > pYLDL > pYIIP. We expressed the R288Q, R288W, L295P, R307G, R307T, Y334S, Y361C, L369F, and 1370M mutants of the Btk SH2 domain identified from XLA patients and measured their binding affinity with the phosphopeptides. Our studies revealed that mutation of R288 and R307 located in the phosphotyrosine binding site resulted in a more than 200-fold decrease in the peptide binding compared to L295, Y334, Y361, L369, and 1370 mutations in the pY + 3 hydrophobic binding pocket (approximately 3- to 17-folds). Furthermore, mutation of the Tyr residue at the betaD5 position reverses the binding order of Btk SH2 domain to pYIIP > pYLDL > pYDEP > pYMEM > pYEEI. This altered binding behavior of mutant Btk SH2 domain likely leads to XLA.

Sleep problems of junior high school students in Taipei.

The objective of this work was to study the relationship between daily sleep time and characteristics of students, e.g. grade level, gender, and academic program. A sleep habit questionnaire was designed to survey students at two junior high schools, one from northern Taipei and the other from southern Taipei. The impact of shortened duration of sleep on daily function was also evaluated. A total of 965 students and their parents were selected randomly in December 1993 for the questionnaire study. The response rate was 96.4% (930) for students and 88.6% (855) for parents. The self-reported daily sleep time of students declined, and daytime sleepiness and moodiness increased in the higher grades. The girls slept fewer hours than the boys and did not show an increase in daytime sleepiness. Those students not taking the senior high school joint entrance examination slept more hours at night and maintained more alertness in the daytime than those who were taking the examination. The more academic pressures that adolescents faced, the fewer hours they slept. Students not participating in the joint entrance examination seemed to show a healthier sleep pattern. Little sleep at night made the students feel sleepy in the daytime and tired, drowsy, moody and difficult at arising in the morning. The reason why girls slept less than boys needs further investigation.

Kleine-Levin syndrome in a boy with Prader-Willi syndrome.

A 9 1/2-year-old Taiwanese boy with Prader-Willi syndrome had the following characteristics: difficulties with sucking, feeding and hypotonia during infancy, a dysmorphic face (triangular mouth, high arched palate, almond-shaped eyes and large head circumference with a relatively narrow bifrontal diameter), borderline intelligence, hypogonadism, hyperphagia, skin picking and truncal obesity. The boy experienced two hypersomnia episodes, at age 8 and 9 years, with both episodes lasting for 10 days. During the two episodes, he was found to have an exacerbated case of hyperphagia, pica, poor emotional control, stereotyped speech and agitated behavior upon awakening. After each episode, the boy had complete remission. Our findings show that the two episodes are compatible with Kleine-Levin syndrome. The relationship between the two syndromes, the Prader-Willi syndrome and the Kleine-Levin syndrome, deserves further study.

The evaluation of percutaneous central venous catheters--a convenient technique in pediatric patients.

OBJECTIVE: To evaluate the feasibility and effectiveness of 3 different types of silastic catheters that were used for percutaneous central venous catheterization (PCVC) through peripheral veins. DESIGN AND SETTING: The study was prospective and consecutive for 6 years at a pediatric/neonatal intensive care unit and pediatric ward in Veterans General Hospital-Taipei, a university-affiliated medical center, in Taiwan, ROC. PARTICIPANTS AND INTERVENTIONS: The patients who had PCVC were consecutively enrolled from January 1988 to December 1993. Three types of silastic catheters were used. The classification was according to the caliber as small catheter (SC, 0.30 mm ID), mid-size catheter (MC, 0.51 mm ID) and large catheter (LC, 0.64 mm ID). The same insertion technique, catheter-through-needle, was used for all PCVC placements through the peripheral vein. After insertion, each catheter was connected to a conventional short cannula (24-, 22-, or 20-gauge) of compatible caliber, and then linked to the infusion system. RESULTS: 1318 PCVCs were used in 1126 consecutive patients, that included 754 SCs in 649 infants (among them 60.9% were less than 1500 g), 383 MCs in 319 toddlers, and 181 LCs in 158 children. Mean (SD) body weight at the time of catheter insertion was SC 1.7(0.9)kg, MC 12.1(6.5)kg and LC 19.3(7.6)kg. Overall, mean (SD) duration of these PCVC was 16.4(8.4) days. A significantly longer duration was noted in: (a) SC group with 19.7(10.4) days than the other two groups [MC 12.4(6.5) days, LC 11.2(5.0) days]; (b) patients with body weight equal to or less than 3.0 kg [18.7(8.6) versus 14.1(6.1); and (c) insertion sites other than external jugular vein (EJV) [18.8(9.7) versus 11.7(6.0)]. These PCVCs provided reliable venous access for multiple purposes such as hyperalimentation, venous access or sampling of blood, antibiotic therapy and chemotherapy. MC and LC were also used for monitoring the central venous pressure. Most of the time, SC and MC were inserted through the superficial peripheral vein of the scalp, neck and extremities, while LC was almost approached via the EJV. The overall success rate of insertion was 92.4% (1318/1427). No significant difference was observed among the different catheter groups [93.4% (754/807) in SC, 90.5% (383/423) in MC and 91.9% (181/197) in LC] and the different insertion sites. Within each group of PCVC, more than eighty percent of catheters were removed electively: 83.3% in SC, 89.6% in MC and 84.5% in LC. Probable catheter-related sepsis accounted for 2.7% (36/1, 318) of all PCVCs. With this study, the cost of each PCVC set is 3.0 US dollar. CONCLUSION: This study indicates that the use of three different calibers of silastic catheter is feasible and effective for PCVC in pediatric practice.

Rates and patterns of comorbidity of adolescent behavioral syndromes as reported by parents and teachers in a Taiwanese nonreferred sample.

OBJECTIVE: To evaluate the rates and patterns of comorbidity between behavioral syndromes in adolescents as reported by parents and teachers. Whether the patterns of comorbidity were "epiphenomenal" was also assessed. METHOD: Parents of 854 randomly selected students (response rate = 88%) in Taipei in 1996 completed the Child Behavior Checklist; among them, 240 also were randomly selected to have the Teacher's Report Form completed by their teachers. In addition to bidirectional comorbidity rates, odds ratios with and without other comorbid pairs controlled for were estimated via multiple logistic regressions. RESULTS: High comorbidity rates between behavioral syndromes were found in adolescents as reported both by parents and teachers except for that of Somatic Complaints with other syndromes. When other comorbidity pairs were controlled for, the comorbidity rates between Anxious/Depressed with externalizing syndromes turned out to be epiphenomenal, whereas those between externalizing syndromes remained high for both informants' reports. Attention Problems also remained significantly comorbid with other syndromes in the multiple logistic regressions except for that of Aggressive Behavior in the Teacher's Report Form sample. CONCLUSION: High comorbidity rates between adolescent behavioral syndromes exist in both parents' and teachers' reports, and it is important to control for the epiphenomenal condition when assessing such comorbidity rates.

Competence and behavioral/emotional problems among Taiwanese adolescents as reported by parents and teachers.

OBJECTIVE: To investigate competence and behavioral/emotional problems among nonreferred adolescents in Taiwan, using a Chinese version of the Child Behavior Checklist (CBCL-C) and the Teacher's Report Form (TRF-C). The psychometric properties of these instruments and cross-cultural differences were also examined. METHOD: Parents of 854 junior high school students aged 12 to 16 years in Taipei, Taiwan, were asked to complete the CBCL-C. Among these students, 162 had their teachers' ratings of the TRF-C. RESULTS: The internal consistency and 1-month test-retest reliability were satisfactory for both the CBCL-C and TRF-C, which were moderately correlated. Both exploratory and confirmatory factor analysis provided some support for the validity of Achenbach's cross-informant model. Parents' reports showed that compared with their American counterparts, Taiwanese adolescents tended to have lower scores on most competence scales, higher scores on scales that reflect covert behavior problems, and lower scores on scales that reflect more overt behavior problems. However, teachers' reports showed no significant differences on most competence and behavior problem scales. CONCLUSION: The CBCL-C and TRF-C are useful tools for assessing the mental health status of Taiwanese adolescents. The cross-cultural differences in adolescent behavior problems are discussed.

Continuous positive airway pressure by nasal prongs in bronchiolitis.

Ten infants with evidence of impending respiratory failure from severe bronchiolitis were successfully treated with continuous positive airway pressure (NCPAP) with double nasal prongs. Their mean (SD) age was 6.7 (3.8) months and mean (SD) body weight was 7.1 (2.1) kg. Respiratory assessments were made immediately before and 2 hours after application of NCPAP. Clinical symptoms, signs, and arterial blood gases improved in all patients, with a significant fall in mean (SD) respiratory rate [71 (6) vs. 54 (9) per minute], mean (SD) heart rate (178(9) vs. 154(15) per minute], and mean (SD) partial pressure of arterial carbon dioxide [Paco2; 48.0 (13.9) vs. 42.4 (12.9) mmHg]. There was a significant rise in mean (SD) arterial blood pH [7.33 (0.05) vs. 7.37 (0.05)] and mean (SD) oxygenation ratio [Fio2/Pao2, 155 (25) vs. 175 (22)]. We believe NCPAP is an effective method, with numerous advantages in the treatment of severe bronchiolitis. Early application of NCPAP is suggested to avoid the need for mechanical ventilation.

Biochemical and molecular characterization of acetylcholinesterase from the hagfish Myxine glutinosa.

To obtain information about the evolution of the cholinesterases, we investigated the cholinesterase activity of an agnathan vertebrate, the hagfish Myxine glutinosa. On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that the cholinesterase activity is due to acetylcholinesterase (AChE). The enzyme hydrolyzes acetylthiocholine preferentially and exhibits substrate inhibition. The hydrolysis of both acetylthiocholine and butyrylthiocholine are inhibited in parallel by cholinesterase inhibitors, with the AChE-specific drug BW284c51 being the most potent; however, this drug and propidium, a peripheral anionic site ligand, are much weaker inhibitors of the hagfish enzyme than of Torpedo AChE. We used sequential extraction, collagenase digestion, and velocity sedimentation on sucrose gradients to determine that the AChE from the skeletal muscle of the hagfish is present in both globular and asymmetric forms. We also used the polymerase chain reaction with degenerate oligonucleotide probes and genomic DNA to obtain a 1 kb gene fragment for hagfish AChE. The enzyme has an acyl binding site typical of other vertebrate AChE, but lacks two aromatic residues implicated in the function of the peripheral anionic subsite. We discuss the relevance of our findings to the evolution of the cholinesterases in the vertebrates.

Stomach rupture associated with physical struggle in a child.

A 5-year-old girl with spontaneous rupture of the stomach was treated successfully with excision of the ischemic edges of the perforation with primary repair. In this case, vigorous resistance against medical measurement resulted in rupture of the stomach, which was already distended with a large amount of fluid and air. The child survived following immediate surgical intervention and intensive postoperative care.

Occupational and environmental lead poisoning: case study of a battery recycling smelter in Taiwan.

The rapid industrialization in Taiwan has caused both prosperity and environmental pollution. The purpose of this study is to demonstrate a case of both occupational and environmental lead poisoning. A patient of lead poisoning initiated a survey of the battery recycling factory, which revealed that 31 of 64 workers suffered from lead poisoning. Children who attended a nearby kindergarten showed a significant increase of blood lead up to 15-25 micrograms/dl and a mild but significant decrease of IQ (intelligent quotient, by Binet-Simon scale) if compared with children of a nonexposed but socioeconomically comparable kindergarten. Outdoor workers of the nearby forging factory also showed a significant increase of blood lead if compared with indoor workers or workers of another nonexposed forging factory 20 Km away. Air sampling showed an average of more than 10 micrograms/m3 in the kindergarten. Soil sampling and analysis also revealed 400 folds increase of lead content, which decreased if the sample was taken deep down to 15-30 cm or 350 meters away from the battery recycling smelter. Moreover, after children were moved away from the pollution source, follow-up examination performed 2.5 years later showed a significant decrease of blood lead and partial recovery of IQ among them.

Locomotor strategies before independent walking: prospective study of 50 mentally retarded children.

To investigate the association between pre-walking locomotor strategies and psychomotor developments in children with mental retardation (MR), 50 children with non-specific MR were included in this study. There were 29 boys and 21 girls, 96% of whom had moderate to severe MR. They were followed from 4-53 months to 25-99 months of age, and their follow-up periods ranged from 10 to 48 months (mean 30 months). According to the pre-walking locomotor strategies, these children were categorized into three groups: the crawling group (n = 34) who used crawling or creeping as their main locomotion pattern before independent walking; the shuffling group (n = 9) who used shuffling prior to independent walking; and the direct-walking group (n = 7) who did not have any other locomotor strategies except rolling. In almost all motor developmental milestones, children in the direct-walking group developed earlier than those in the crawling and shuffling groups. Children in the crawling group had more advanced developments than those in the shuffling group. The difference in the mean ratio developmental quotients of the Bayley Mental Scale among the three groups was not significant. The present study showed that crawling may not be a necessary prerequisite for early ambulation or better cognitive function in MR children.

Intellectual outcomes of patients with congenital hypothyroidism not detected by neonatal screening.

Mental retardation is a major sequela of delayed treatment of congenital hypothyroidism. In this study, we investigated the intellectual outcomes of patients with congenital hypothyroidism diagnosed before a nationwide screening project started. Eighty-two patients had intelligence tests done while in the euthyroid state. Their mean intelligence quotient (IQ) was 78 +/- 21 (+/- SD) (n = 79). The mean verbal IQ was significantly higher than the mean full-scale IQ. The mean IQs of both ectopic thyroid (84 +/- 21, n = 28) and dyshormonogenic patients (85 +/- 14, n = 18) were significantly higher than that of patients with athyrosis (64 +/- 18, n = 19) (p < 0.05). Patients who were treated before 3 months of age had significantly higher mean IQs (90 +/- 16, n = 16) than those treated after 3 months (75 +/- 21, n = 63) (p < 0.01). Our results confirm that both patients with ectopic thyroids and those with dyshormonogenesis have better intellectual outcomes than athyrotic patients do, and that early treatment improves the intellectual outcome of patients with congenital hypothyroidism.

Intellectual outcome of patients with congenital hypothyroidism detected by neonatal screening.

BACKGROUND AND PURPOSE: Mental retardation is a major sequela of delayed treatment for congenital hypothyroidism; congenital hypothyroidism can be treated early if detected with neonatal screening. We evaluated the intellectual outcomes of 62 patients with congenital hypothyroidism detected by neonatal screening at a major teaching hospital in northern Taiwan. The effects of thyroid pathology, age at the initiation of treatment, socioeconomic status, and severity of hypothyroidism on intellectual outcome were also analyzed. METHODS: All patients had euthyroid status at the time of intelligence testing. The Chinese Fourth Revision of the Binet-Simon Scales was used to evaluate the patients' intelligence between the ages of 3 and 6 years. RESULTS: The mean intelligence quotient (IQ) score was 102 +/- 18. Only four of the 62 patients were mentally retarded. Patients with lower initial serum thyroxine concentrations (T4; < 2 micrograms/dL) at the time of diagnosis of congenital hypothyroidism had significantly lower IQs (95 +/- 19, n = 26) than those with higher initial T4 concentrations (106 +/- 16, n = 36; p < 0.05). Patients with fewer than three ossification centers had lower IQs (91 +/- 20, n = 12) than those with three or more (104 +/- 17, n = 36; p < 0.05). Significantly lower IQs were also found in patients with a smaller femoral epiphysis area (< 0.1 cm2) (92 +/- 20, n = 15) than in those with larger epiphyses (106 +/- 15, n = 21; p < 0.05). The type of pathology (ectopia, athyrosis, dyshormonogenesis), age at the start of treatment (before or after 30 days of age), and socioeconomic status did not significantly affect the intellectual outcome. CONCLUSIONS: Our results indicate that intellectual outcome in Taiwanese patients with congenital hypothyroidism has been improved by neonatal screening and that the severity of hypothyroidism at diagnosis is the most important prognostic factor affecting intellectual outcome in these patients.

Dentine lead and child intelligence in Taiwan.

It is well known that lead is a developmental neurotoxin, but, because many factors influence a child's development, a safe level of lead for children is still not clear. In this study, personal lead exposure was assessed. A total of 940 deciduous teeth--mostly incisors--was collected from 764 children in grades 1-3 who attended 7 primary schools. Two of the primary schools were near smelters, 4 were in Taipei City, and 1 was located in a coastal village. Teachers were provided with a questionnaire about classroom performance, and 97% completed and returned the questionnaire to the laboratory. Parents were given a questionnaire about family background, pregnancy, and health history (92% returned). Dentine lead levels of shed incisors for children in Taipei City were higher than levels reported in Boston, i.e., mean (standard deviation) of 4.4 (3.5) versus 3.3 (2.5) micrograms/g, respectively (p less than .001). The lead values were significantly higher in children who attended school near a smelter than in children who attended school in Taipei City: 6.3 (3.3) (p less than .001). The mean lead levels in children who attended school in a coastal village was 5.1 (2.8). The ranges for all schools overlapped, which indicated that there were multiple lead sources. Intelligence scores from Raven's Colored Progressive Matrices Test were negatively correlated with lead levels, especially among girls and among children whose parents had less education. We adjusted for other risk factors--most notably parental education, which correlates inversely with lead levels--and found that the role of the lead term was lowered but not eliminated.

Long-term effect of increased lead absorption on intelligence of children.

The authors examined the reversibility of cognitive impairment caused by a mild increase in lead absorption among children. The results of our initial study revealed that air and soil outside a lead-recycling plant in Taiwan were seriously contaminated by lead, which was associated with lowered intelligence quotients of 32 children who attended a nearby kindergarten (i.e., kindergarten A). Thirty-five children-who were comparable with respect to age, sex, birth order, sibling number, and parental education level-from another kindergarten (i.e., kindergarten B) located 5 km from the plant were enrolled as the reference group. Following the initial study, kindergarten A school children moved 2 km from the lead-recycling plant. Twenty-eight children in each group were followed successfully 2.5 y later. Blood lead, intelligence quotient, and intelligence quotient-related factors were reassessed. The results showed that the average blood lead level of the exposed pupils dropped 6.9 microg/dl (standard deviation [SD] = 3.9 microg/dl) (p < .001), and the average intelligence quotient increased 11.7 points (SD = 13.2) (p < .01), compared with the results of the initial study. The average blood lead level of the reference group decreased by 1.7 microg/dl (SD = .1.3) (p < .001), whereas the average intelligence quotient increased by 4.2 points (SD = 13.8) (p = .115). There was a significant difference in intelligence quotients between the two groups during the initial study, but the difference subsequently disappeared during the follow up. The authors concluded that intelligence quotient impairment, caused by a mild subclinical elevation of blood lead (i.e., likely no more than 30 microg/dl) for a period of 1-3 y in 3- to 5-y-olds, is at least partially reversible.