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.

Self-efficacy outcomes of people with brain injury in cognitive skill training using different types of trainer-trainee interaction.

PRIMARY OBJECTIVE: To evaluate the effects of different trainer-trainee interaction patterns on the self-efficacy outcomes of trainees with brain injury. RESEARCH DESIGN: A pre-test and post-test randomized clinical trial design. METHODS AND PROCEDURES: One hundred and three subjects with brain injury were recruited and 83 subjects participated in analogical problem-solving training that was delivered in three respective interaction modes: (a) direct trainer-trainee interaction, (b) self-paced computer-assisted and (c) on-line training with real-time audio-visual interaction. Quizzes on daily behavioural problem- solving and a problem-solving self-efficacy rating scale were adopted as outcome measures. The trainees in the trainer-administered group that received instructions in person with a continuous 'human touch' showed more significant improvement in their problem-solving self-efficacy than the two other groups. CONCLUSIONS: Interactive modes of cognitive skill training can be flexible enough to match the needs of individual trainees. However, human interaction is considered important in promoting self-efficacy in trainees with brain injury.

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.

Local interstitial emphysema caused by meconium aspiration: report of one case.

A neonate of meconium aspiration syndrome presented with respiratory distress and bilateral pneumothorax. The image studies, including chest X-ray, chest computed tomography and operation finding all showed cystic changes in the right lung. Therefore congenital cystic lesions of lung was the first impression. However, the pathologic report disclosed meconium aspiration with interstitial emphysema.

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.

Intratracheal oxygen administration during bronchoscopy in newborns: comparison between two different weight groups of infants.

BACKGROUND: The development of ultrathin fiberoptic bronchoscopy (FB) has made the examination of neonatal airways a practical possibility. The aim of this study was to assess the effects of intratracheal oxygen (ITO) administration on blood oxygenation and carbon dioxide (CO2) changes during FB in different body-weight infants. METHODS: Newborns suspected of having airway problems, but in a stable cardiopulmonary condition were studied. An ultrathin (outside diameter, 2.2 mm) fiberoptic bronchoscope that was modified by adding an external tube (internal diameter, 0.3 mm; outside diameter, 0.64 mm) to deliver oxygen was used. For ITO administration, a low oxygen flow rate of 0.1 l/kg/min was delivered directly into the trachea. Oxygenation and CO2 measurements were obtained at five different stages: 1) just before FB (baseline); 2) with the tip of the bronchoscope at the supralarynx; 3) with the tip at the carina without ITO; 4) with the tip at the carina with ITO; and 5) 15 minutes after FB. Forty infants were studied completely and divided into two groups according to their body weight: 1) the light-weight group (< 2,500 g), 21 infants; and 2) the heavy-weight group (> or = 2,500 g), 19 infants. RESULTS: In both groups, arterial blood oxyhemoglobin saturation and oxygen tension decreased significantly (p < 0.05) when the tip of the bronchoscope advanced from the nostril to the supralarynx, and further decreased (p < 0.01) when at the carina level. Small infants had greater decrements of both oxygenation measurements (p < 0.05) than the large infants. After ITO administration, both oxygenation measurements increased significantly (p < 0.001) and returned to baseline following FB. Both end tidal pressure of CO2 (P(ET)CO2) and arterial CO2 tension (PaCO2) significantly increased from the baseline when the FB tip was advanced from the supralarynx to the carina (p < 0.05). During ITO administration, the PaCO2 increased (p < 0.01) but the P(ET)CO2 decreased (p < 0.001). After FB, both CO2 measurements returned to baseline. The pH only decreased during ITO administration. CONCLUSIONS: We conclude that FB causes significant hypoxemia and hypercapnia in newborns, especially in underweight infants. Appropriate ITO can be considered a safe and beneficial technique for maintaining oxygenation during FB. P(ET)CO2 monitoring may mask true blood CO2 retention during ITO administration.

Captopril suppression tests in normotensive individuals.

OBJECTIVE: We aimed to measure the serial (time related) concentrations of aldosterone and renin after a single dose of 25 mg of captopril in normotensive individuals. With these results, we aim to ascertain the best sampling times for future tests. DESIGN: Six normotensive subjects were studied under two different conditions--once in a supine position and once under normal (erect-position) activity. Each subject was given 25 mg of captopril and his serum aldosterone and renin concentrations measured at half hourly intervals for four hours. Simultaneous half hourly blood pressure measurements were also noted. RESULTS: All subjects showed suppression of aldosterone levels with ingestion of captopril, and in the supine position maximal suppression was consistently observed from the 3rd to the 4th hour after ingestion. When studied in the erect posture, although there was significant suppression, this was not sustained, and a paradoxical rise of aldosterone levels was seen after 2 hours. Renin activity measured during this study showed no consistent patterns. The renin levels were unchanged in almost 40 per cent of cases, and raised in about 60 per cent of cases. None of the subjects had symptomatic postural hypotension after 25 mg of captopril. CONCLUSIONS: The captopril suppression test is safe and effective in assessing the suppressibility of aldosterone and the period of maximal suppression is from the 3rd to the 4th hour after oral ingestion of captopril.

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.

Infection of human T lymphocytes with varicella-zoster virus: an analysis with viral mutants and clinical isolates.

Varicella-zoster virus (VZV) disseminates in the body in peripheral blood mononuclear cells during chickenpox. Up to 1 in 10,000 mononuclear cells are infected during the viremic phase of the disease. We developed an in vitro system to infect human mononuclear cells with VZV by using umbilical cord blood. In this system, 3 to 4% of T cells were infected with VZV. VZV mutants unable to express certain genes, such as open reading frame 47 (ORF47) or ORF66, were impaired for growth in T cells, while other mutants showed little difference from parental virus. VZV unable to express ORF47 was even more impaired for spread from umbilical cord blood cells to melanoma cells in vitro. Early-passage clinical isolates of VZV infected T cells at a similar rate to the Oka vaccine strain; however, the clinical isolates were more efficient in spreading from infected T cells to melanoma cells. This in vitro system for infecting human T cells with VZV should be useful for identifying cellular and viral proteins that are important for virus replication in T cells and for the spread of virus from T cells to other cells.

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.

Psychiatric comorbidity of adolescents with sleep terrors or sleepwalking: a case-control study.

OBJECTIVE: This study investigated the psychiatric comorbidity, personality traits and family history of adolescents with sleep terrors and/or sleepwalking. METHOD: Thirty students with sleep terrors and/or sleepwalking and 30 classroom controls were selected on the basis of a sleep habit questionnaire. After completing the Junior Eysenck Personality Inventory (JEPI), the 60 subjects were interviewed by the first author with the Chinese-version Kiddie-SADS-E (Schedule for Affective Disorders and Schizophrenia for Children--Epidemiology Version). All subjects and their parents were interviewed for the subjects' sleep habits, sleep disorders, and personality characteristics in the previous year. The case and the control groups were divided based on whether the sleep terrors and/or sleepwalking had occurred in the previous year. There were 21 case and 30 control subjects in the final data analysis. RESULTS: The case group had more psychiatric diagnoses and problems; there were statistically significant differences in overanxious disorder, panic disorder, simple phobia and suicidal thoughts between the two groups. The case group had more sleeptalking and nightmares during the previous year as well as more enuresis in earlier years. From their parents' perspective, the case group was more nervous and pessimistic. The results of the JEPI showed a high neuroticism score in the case group. There was an increased familial occurrence of these two sleep disorders. CONCLUSIONS: Adolescents with sleep terrors and sleepwalking were found to have an increased prevalence of other sleep disorders, neurotic traits, and psychiatric disorders and problems. Whereas sleep terrors and sleepwalking in childhood are related primarily to genetic and developmental factors, their persistence and, especially, their onset in adolescence may be related to psychological factors.

Bacterial contamination of propofol in the operating theatre.

There have been several reports of propofol becoming extrinsically contaminated with bacteria. These reports have usually related to infusions or delays in administration after the ampoule has been opened. This observational study was performed to examine bacterial contamination of propofol during usual practice in the operating theatres of a single large hospital group. One hundred samples of propofol were collected and cultured. Samples were taken immediately after administration in cases where the delay between opening the ampoule and administration was at least 15 minutes. The samples were classified according to whether the propofol was kept in the ampoule or a syringe after opening the ampoule and whether the intended use was for a single patient or multiple patients. The time between opening the ampoule and administration was recorded. There were three positive bacterial cultures. These samples all came from ampoules used for more than one patient, without the later dose (does) being drawn into a syringe at the time the ampoule was opened. This common clinical practice, especially in paediatric anaesthesia, does not comply with the manufacturer's recommendations. The clinical significance of the bacterial contamination detected is not clear. It is recommended that propofol should be handled in an aseptic fashion and measures taken to minimize the risk of bacterial contamination.

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.

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.

Diagnosis of zygosity by questionnaire and polymarker polymerase chain reaction in young twins.

We developed a zygosity questionnaire for use in young twins and assessed its validity using the results of DNA diagnosis. The participants were divided into two groups: 105 pairs of adolescent twins (12-16 years old), 47 pairs of child twins (2-12 years old), and their respective parents. The DNA diagnosis of zygosity was made with polymarker polymerase chain reaction (PCR) amplification of five loci, using the AmpliType PM PCR Amplification and Typing Kit; this method has an accuracy rate of 99.0%. A parsimonious model for each sample was established using stepwise logistic regression analysis of the 20 items of the questionnaire. The total accuracy rate of the model was satisfactory for both parental reports (three items) and self-reports (three items) of adolescent twins (97.4 and 95.6%, respectively), while that for parental reports on child twins (two items) was less satisfactory (92.5%). For adolescent twins, if DNA diagnostic workups were limited to those with discordant reports either from themselves or from their parents, the accuracy rate increased to 100% for parental reports and 98% for self-reports.