Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Genetic covariance between indices of body condition and immunocompetence in a passerine bird

Background: Condition-dependence is a ubiquitous feature of animal life histories and has important implications for both natural and sexual selection. Mate choice, for instance, is typically based on condition-dependent signals. Theory predicts that one reason why condition-dependent signals may be special is that they allow females to scan for genes that confer high parasite resistance. Such explanations require a genetic link between immunocompetence and body condition, but existing evidence is limited to phenotypic associations. It remains unknown, therefore, whether females selecting males with good body condition simply obtain a healthy mate, or if they acquire genes for their offspring that confer high immunocompetence. Results: Here we use a cross-foster experimental design to partition the phenotypic covariance in indices of body condition and immunocompetence into genetic, maternal and environmental effects in a passerine bird, the zebra finch Taeniopygia guttata. We show that there is significant positive additive genetic covariance between an index of body condition and an index of cell-mediated immune response. In this case, genetic variance in the index of immune response explained 56% of the additive genetic variance in the index of body condition. Conclusion: Our results suggest that, in the context of sexual selection, females that assess males on the basis of condition-dependent signals may gain genes that confer high immunocompetence for their offspring. More generally, a genetic correlation between indices of body condition and imuunocompetence supports the hypothesis that parasite resistance may be an important target of natural selection. Additional work is now required to test whether genetic covariance exists among other aspects of both condition and immunocompetence.

Physiologic parameters that affect pulse transit time difference between the upper and lower limbs in children

Pulse wave velocity (PWV) is a known parameter that is related to arterial distensibility. However, its potential is hampered by the absence of appropriate techniques to estimate it noninvasively. PWV can be used as an assessment of increased arterial stiffness that is linked to systolic hypertension, excess cardiovascular morbidity and mortality.(1,2)

No association between the deficit syndrome in psychosis and summer birth in a Southern Hemisphere country (Correspondence)

This Article does not have an abstract.

Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance

Infections caused by the yeast Candida albicans represent an increasing threat to debilitated and immunosuppressed patients, and neutropenia is an important risk factor. Monoclonal antibody depletion of neutrophils in mice was used to study the role of these cells in host resistance. Ablation of neutrophils increased susceptibility to both systemic and vaginal challenge. The fungal burden in the kidney increased threefold on day 1, and 100-fold on day 4, and infection was associated with extensive tissue destruction. However, a striking feature of the disseminated disease in neutrophil-depleted animals was the altered pattern of organ involvement. The brain, which is one of the primary target organs in normal mice, was little affected. There was a threefold increase in the number of organisms recovered from the brains of neutrophil-depleted mice on day 4 after infection, but detectable abscesses were rare. In contrast, the heart, which in normal mice shows only minor lesions, developed severe tissue damage following neutrophil depletion. Mice deficient in C5 demonstrated both qualitative and quantitative increases in the severity of infection after neutrophil depletion when compared with C5-sufficient strains. The results are interpreted as reflecting organ-specific differences in the mechanisms of host resistance.

Falling incidence of amputations for peripheral occlusive arterial disease in western Australia between 1980 and 1992

Objectives: To assess temporal trends in the incidence of surgical procedures for peripheral occlusive arterial disease (POAD) and associated changes in outcome as measured by the rate of major lower limb amputations for POAD. Design: a retrospective descriptive population-based study was conducted of the geographically isolated population of Western Austrialia between 1980 and 1992. Methods: Vascular procedures with an accompanying diagnosis of POAD were identified in a computerised system of name-identified records of all discharges from hospital for the population. These procedures were detected using relevant codes from the International Classification of Disease and Procedures. Records of angioplasty and thrombolysis procedures were augmented by searches of hospital-based registers of invasive radiological procedures. The data for the remaining procedures were validated by a review of a random sample of medical records. Results: over the 13 years of the study, rates of major amputations fell significantly for in non-amputation vascular surgery for individuals under the age of 60. In addition, rather than an overall rise in surgery there was shift away from sympathectomy and thromboendarterectomy to angioplasty and bypass surgery. Furthermore, an increasing proportion of all major amputations had a prior attempt at arterial reconstruction. Conclusion: These observations suggest the decrease in major amputations for POAD may reflect a fall in the incidence of POAD, possibly aided by move effective surgery, rather than increased rates of vascular surgery.

Investigation of the relationship between protein, message and inducer concentrations in recombinant E-coli cells

Chloramphenicol acetyl transferase (CAT) protein and mRNA levels in E. coli were determined following induction of a tac::cat construct by isopropyl-beta-thiogalactopyranoside (IPTG). High cat mRNA levels did not directly reflect CAT protein levels, in either shakeflask experiments or fermentations. Furthermore, concentrations of IPTG resulting in the highest levels of expression of cat mRNA, were different to those resulting in highest levels of CAT protein. The data suggest that high transcriptional activities lead to limitations at the translational level.

Transitions between routes of benzodiazepine administration among heroin users in Sydney

A sample of 312 heroin users were interviewed regarding their benzodiazepine use. The majority (94%) had used benzodiazepines, 72% in the 6 months prior to interview. Benzodiazepine injecting was common, with 28% of the sample having injected these drugs, 13% in the 6 months preceding interview. Current benzodiazepine injectors showed greater polydrug use, injection-related HIV risk-taking behaviour, criminal involvement, psychological distress and injection-related health problems, as well as poorer general health, and an increased risk of having overdosed than other users of benzodiazepines. Of those subjects who had injected benzodiazepines, 55% were no longer current benzodiazepine injectors. Concern for general health emerged as the most common reason for having made a transition away from injecting, and for being likely to make such a transition.

Relationship between use of technology and employment rates for people with physical disabilities in Australia: Implications for education and training programmes

This study examined the impact of computer and assistive device use on the employment status and vocational modes of people with physical disabilities in Australia. A survey was distributed to people over 15 years in age with physical disabilities living in the Brisbane area. Responses were received from 82 people, including those with spinal cord injuries, cerebral palsy and muscular dystrophy. Of respondents 46 were employed, 22 were unemployed, and 12 were either students or undertaking voluntary work. Three-quarters of respondents used a computer in their occupations, while 15 used assistive devices. Using logistic regression analysis it was found that gender, education, level of computer skill and computer training were significant predictors of employment outcomes. Neither the age of respondent nor use of assistive software were significant predictors. From information obtained in this study guidelines for a training programme designed to maximize the employability of people with physical disabilities were developed.