Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

ITERATIVE DYNAMIC PROGRAMMING FOR MINIMUM ENERGY CONTROL PROBLEMS WITH TIME DELAY

This paper presents the use of iterative dynamic programming employing exact penalty functions for minimum energy control problems. We show that exact continuously non-differentiable penalty functions are superior to continuously differentiable penalty functions in terms of satisfying final state constraints. We also demonstrate that the choice of an appropriate penalty function factor depends on the relative size of the time delay with respect to the final time and on the expected value of the energy consumption. A quadratic approximation (QA) of the delayed variables is much better than a linear approximation (LA) of the same for relatively large time delays. The QA improves the rate of convergence and avoids the formation of ‘kinks‘. A more general way of selecting appropriate penalty function factors is given and the results obtained using four illustrative examples of varying complexity corroborate the efficacy of the method.     

Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Safety of levocetirizine treatment in young atopic children: An 18-month study

There are more than 40 H(1)-antihistamines available worldwide. Most of these medications have never been optimally studied in prospective, randomized, double-masked, placebo-controlled trials in children. The aim was to perform a long-term study of levocetirizine safety in young atopic children. In the randomized, double-masked Early Prevention of Asthma in Atopic Children Study, 510 atopic children who were age 12-24 months at entry received either levocetirizine 0.125 mg/kg or placebo twice daily for 18 months. Safety was assessed by: reporting of adverse events, numbers of children discontinuing the study because of adverse events, height and body mass measurements, assessment of developmental milestones, and hematology and biochemistry tests. The population evaluated for safety consisted of 255 children given levocetirizine and 255 children given placebo. The treatment groups were similar demographically, and with regard to number of children with: one or more adverse events (levocetirizine, 96.9%; placebo, 95.7%); serious adverse events (levocetirizine, 12.2%; placebo, 14.5%); medication-attributed adverse events (levocetirizine, 5.1%; placebo, 6.3%); and adverse events that led to permanent discontinuation of study medication (levocetirizine, 2.0%; placebo, 1.2%). The most frequent adverse events related to: upper respiratory tract infections, transient gastroenteritis symptoms, or exacerbations of allergic diseases. There were no significant differences between the treatment groups in height, mass, attainment of developmental milestones, and hematology and biochemistry tests. The long-term safety of levocetirizine has been confirmed in young atopic children.     

现代中医药发展战略思考

建国几十年来，由于党和政府的大力提倡和扶持，中医药得到了很大发展，但相对于西医的发展势头仍显不足。尤其是近10多年来，由于现代科技及现代管理学的有力推动，西医获得了突飞猛进的发展，然而，中医却由于种种原因发展相对缓慢。在这各行各业竞相发展的现代社会，中医要生存，就蓝须发展，中医要发展，就妊须总揽全局，从战略高度克服中医药发展的各种不利因素，充分发挥各方面的有利条件。     

Parenting children with and without developmental delay: the role of self-mastery

Background While parenting behaviours have direct effects on children’s behavioural outcomes, other, more distal factors also may be shaping the way a mother handles parenting responsibilities. Dispositional factors are likely to be a major influence in determining how one parents. Although researchers have studied the relationships among maternal dispositional factors, parenting, and child behaviours, few studies have examined these relationships when the child is at developmental risk. Children with developmental delays evidence elevated clinical level behaviour problems, so this group is of primary interest in the search for precursors to psychopathology. The present study examined how the maternal dispositional trait of self‐mastery, as well as supportive and non‐supportive parenting, relate to behaviour problems in young children with and without developmental delay. Method Participants were 225 families, drawn from Central Pennsylvania and Southern California. The children, all aged 4 years, were classified as delayed (n = 97) or non‐delayed (n = 128). The Self‐Mastery Scale measured perceived level of control over life events. The Coping with Children’s Negative Emotions Scale measured different ways parents perceive themselves as reacting to their children’s distress and negative affect. The Child Behavior Checklist assessed children’s behaviour problems. Results Delayed condition mothers reported significantly more child behaviour problems than non‐delayed condition mothers; the two conditions did not differ in self‐mastery, supportive parenting, or non‐supportive parenting. Self‐mastery, non‐ supportive parenting reactions, and child behaviour problems all related significantly to one another. For the sample as a whole and within the delayed condition, the association between self‐mastery and child behaviour problems was partially mediated by non‐supportive parenting reactions, although self‐mastery was still significantly associated with problem behaviour. In the non‐delayed condition, although significant relationships also were found among the variables of interest, non‐supportive parenting did not have a significant main or mediation effect. Delay status moderated the relationship between negative parenting reactions and child behaviour problems, assessed by the Child Behavior Checklist Total and Internalizing scores. When mothers displayed low levels of non‐supportive reactions, children in the delayed and non‐delayed groups had similar levels of total problem behaviour. However, when mothers were medium or high in non‐supportive reactions, children in the delayed group had much higher levels of problem behaviours than those in the non‐delayed group. Conclusions The present study extended research on parental dispositional factors and parenting by measuring self‐mastery as a global personality trait rather than measuring self‐efficacy related specifically to childrearing. Moreover, relationships were examined for both developmentally delayed and non‐delayed samples, allowing for a clearer understanding of the influences on problem behaviours in children with developmental delays. The findings support the view that parenting behaviours have a greater impact on children at developmental risk.     

Q-tip pap smear: Should it be done routinely in patients who have developmental disabilities?

In some patients with mental retardation, a Q-tip pap smear obtained blindly from the upper vagina may be the only cytologic smear obtainable without subjecting the patient to heavy sedation or to examination under anesthesia. The efficacy of blind Q-tip smears has not been previously determined. Of 31 Q-tip smears obtained from patients with CIN, the Q-tip smear identified the abnormality in 10 (32%) patients. For those patients who will not submit to examination without anesthesia or sedation, routine screening with multiple smears, obtained on an annual basis has the potential to identify many cases of CIN which otherwise would not be identified at all, and in certain patients, this method outweighs the risks of heavy sedation or general anesthesia. Because of the greatly reduced sensitivity of the Q-tip pap, every effort should be made to help the patient and/or her family or guardian to understand the implications and risks of this method. However, if an examination under anesthesia is performed for other indications, a complete gynecologic examination and a direct smear should be obtained at that time.