Movement-related potentials in Parkinson's disease: External cues and attentional strategies

Hypokinetic movement can be greatly improved in Parkinson's disease patients by the provision of external cues to guide movement. It has recently been reported, however, that movement performance in parkinsonian patients can be similarly improved in the absence of external cues by using attentional strategies, whereby patients are instructed to consciously attend to particular aspects of the movement which would normally be controlled automatically. To study the neurophysiological basis of such improvements in performance associated with the use of attentional strategies, movement-related cortical potentials were examined in Parkinson's disease and control subjects using a reaction time paradigm. One group of subjects were explicitly instructed to concentrate on internally timed responses to anticipate the presentation of a predictably timed go signal. Other subjects were given no such instruction regarding attentional strategies. Early-stage premovement activity of movement-related potentials was significantly increased in amplitude and reaction times were significantly faster for Parkinson's disease subjects when instructed to direct their attention toward internally generating responses rather than relying on external cues. It is therefore suggested that the use of attentional strategies may allow movement to be mediated by less automatic and more conscious attentional motor control processes which may be less impaired by basal ganglia dysfunction, and thereby improve movement performance in Parkinson's disease.

Metal-centred versus ligand-centred luminescence quenching of a macrocyclic copper(II) complex

The new macrocyclic ligand trans-6-(9-anthracenylmethylamino)-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecan-13-amine has been synthesized and characterised as its copper(II) complex and the crystal structure of this complex has been determined. Fluorescence of the anthracenyl group of the macrocycle is quenched in its free base form and when complexed with Cu-II. Fluorescence returns when Lewis acids such as H+ and Zn-II are added to solutions of the ligand, indicating that photoinduced electron transfer from the amine lone pairs is responsible for fluorescence quenching in the free base form. By contrast, fluorescence of the complex is quenched by intramolecular electronic energy transfer.

Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor

Four discontinuous extracellular sequence domains have been proposed to form the ligand binding sites of the ligand-gated ion channel receptor superfamily. In this study, we investigated the role of 12 contiguous residues of the inhibitory glycine receptor that define the proposed loop A ligand binding domain; Using the techniques of site-directed mutagenesis and patch-clamp electrophysiology, four of the 12 residues were shown to have impaired ligand binding. Three mutants, I93A, A101H, and N102A, resulted in significant (17-44-fold) increases in the agonist EC50 values as compared with the wild-type glycine receptor, whereas Hill coefficients, I-max values, and antagonist affinity remained largely unaffected. Consideration of receptor efficacy values indicates that these residues are involved in ligand binding rather than channel activation. A fourth mutant, W94A, failed to give rise to any glycine-activated currents, although cell-surface expression was observed, suggesting that this residue may also be involved in agonist binding. These data provide the most extensive characterization of the loop A ligand binding domain available to date and define two new residue locations, Ile(93) and Asn(102), as contributing to the four-loop model of ligand binding.

Ameloblast apoptosis and IGF-1 receptor expression in the continuously erupting rat incisor model

Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are hard wired for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.

Treads in opiate-related deaths in the United Kingdom and Australia, 1985-1995

This paper compares data on rates of opiate overdose mortality in the UK and Australia between 1985 and 1995. Data on rates of ICD 9-coded overdose mortality were obtained from the Office of National Statistics in the UK and from the Australian Bureau of Statistics mortality register. The proportion of all deaths attributed to opioid overdose increased in both countries between 1985 and 1995. The proportion of all deaths attributed to opioid overdose was substantially higher in Australia than in the UK, but methadone appeared to contribute to more opioid overdose deaths in the UK (50%) than in Australia (18%). Given deficiencies in the available data, the reasons for these differences between the two countries are uncertain but a plausible hypothesis is that the greater availability and ease of access to methadone maintenance in the UK contributes to both the lower rate of opioid overdose mortality and the greater apparent contribution that methadone makes to opioid overdose deaths in that country. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Expression of EphA5 during development of the olfactory nerve pathway in rat

The olfactory neuroepithelium is a highly plastic region of the nervous system that undergoes continual turnover of primary olfactory neurons throughout life. The mechanisms responsible for persistent growth and guidance of primary olfactory axons along the olfactory nerve are unknown. In the present study, we used antibodies against the Eph-related receptor, EphA5, to localise EphA5, and recombinant EDhA5-IgG fusion protein to localise its ligands. We found that although both EphA5 and its ligands were both expressed by primary olfactory neurons within the embryonic olfactory nerve pathway, there was no graded or complementary expression pattern. In contrast, the expression patterns altered postnatally such that primary olfactory neurons expressed the ligands, whereas the second-order olfactory neurons, the mitral cells, expressed EphA5. The role of EphA5 was analysed by blocking EphA5-ligand interactions in explant cultures of olfactory neuroepithelium using anti-EphA5 antibodies and recombinant EphA5. These perturbations reduced neurite outgrowth from explant cultures and suggest that intrafascicular axon repulsion may serve to limit adhesion and optimise conditions for axon growth. (C) 2000 Wiley-Liss, Inc.

Chemical synthesis, characterization and activity of RK-1, a novel alpha-defensin-related peptide

The 32-residue peptide, RK-1, a novel kidney-derived three disulfide-bonded member of the antimicrobial alpha-defensin family, was synthesized by the continuous now Fmoc-solid phase method. The crude, cleaved and S-reduced Linear peptide was both efficiently folded and oxidized in an acidic solution of aqueous dimethyl sulfoxide. Following purification of the resulting product, it was shown by a variety of analytical techniques, including matrix assisted laser desorption time of flight mass spectrometry, to possess a very high degree of purity. The disulfide bond pairing of the synthetic peptide was determined by H-1-NMR spectroscopy and confirmed to be a Cys(1)-Cys(6), Cys(2)-Cys(4), Cys(3)-Cys(5) arrangement similar to other mammalian alpha-defensin peptides. The synthetic RK-1 was also shown to inhibit the growth of Escherichia coli type strain NCTC 10418, Copyright (C) 2000 European Peptide Society and John Wiley & Sons, Ltd.

Patterns of alcohol consumption in young Australian women: socio-demographic factors, health-related behaviours and physical health

Objective: To determine which sociodemographic factors. health-related behaviours and physical health conditions are associated with non-drinking, binge drinking and hazardous/harmful drinking in young Australian women. Methods: Cross-sectional data were obtained from the baseline survey of 14,762 young women (aged 18-23 years) enrolled in the Women's Health Australia study in 1996. Associations between a range of drinking patterns and sociodemographic factors, health-related behaviours and health conditions were examined. Results: Half the women were 'low intake' drinkers, a third 'rarely drank' and 9% were non-drinkers; however, 70% reported binge drinking with one-quarter of the binge drinkers doing so at least weekly. Nondrinkers were more likely than drinkers to be married, pregnant, non-smokers, born in non-English speaking countries, to live in the Northern Territory, and to have lower levels of education, employment, and private health insurance. Low intake/binge weekly' drinkers (12%) and 'hazardous/ harmful' drinkers (5%) were more likely than 'low risk' drinkers to be unmarried; to live in shared accommodation, alone or with their parents; to live in rural or remote areas; to have ever had any sexually transmitted infection; to be current smokers or ex-smokers and to have used unhealthy weight-control practices. Conclusions: The results confirm findings from other countries about the importance of social conditions as determinants of alcohol consumption by young women. Implications: Health promotion to reduce young women's alcohol consumption needs to be carefully targeted to take account of their demographies, living environments and beliefs.

First-instar morphology and sexual dimorphism in the gall-inducing scale insect Apiomorpha Rubsaamen (Hemiptera : Coccoidea : Eriococcidae)

Sexual dimorphism among crawlers of the scale insect family Eriococcidae is reported for the first time. The general morphology of crawlers of the gall-inducing genus Apiomorpha (Eriococcidae) is presented and sexual dimorphism described. Sexual dimorphism appears to be associated with differential dispersal and settling-site preference of the sexes during the crawler stage. First-instar males of the A. pharetrata and A. munita species-groups settle only on the galls induced by their mothers or, in the case of A. munita, also galls of nearby females, whereas female crawlers disperse. Female crawlers of all species of Apiomorpha, and male crawlers of most species, are well suited for air-borne dispersal. It is suggested that sexual dimorphism among crawlers of Apiomorpha, and some other scale insects, is the result of loss or reduction of those morphological features associated with dispersal. In addition, male crawlers of some species of Apiomorpha have sensory structures which may assist in the detection of sex-specific settling sites.

Challenge of reducing drug-related deaths

The public-health attention given to deaths caused by illicit drug use in general, and by drug overdose in particular, should be commensurate with their contribution to premature death. For too long these deaths have been regarded as an unavoidable hazard of illicit drug use, their neglect abetted by the implicit view that the lives of illicit drug users are less deserving of being saved than those of others. In its report published this week,1 the UK Advisory Council on the Misuse of Drugs (ACMD) has rejected these implicit assumptions. Its view is that “drug-related deaths can, will and must in the near future be radically reduced in number”. It points out that the effort that society expends on preventing premature deaths “should apply no less to drug misusers than it does to other classes of people”.1

Ni-II and Zn-II complexes of the hexadentate macrocyclic ligand cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetra- decane-6,13-diamine

The title pendent-arm macrocyclic hexaamine ligand binds stereospecifically in a hexadentate manner, and we report here its isomorphous Ni-II and Zn-II complexes (both as perchlorate salts), namely (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)nickel(II) diperchlorate, [Ni(C12H30N6)](ClO4)(2), and (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)zinc(II) diperchlorate, [Zn(C-12 H30N6)](ClO4)(2). Distortion of the N-M-N valence angles from their ideal octahedral values becomes more pronounced with increasing metal-ion size and the present results are compared with other structures of this ligand.

Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study

Background and Purpose-Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic Factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia. Methods-Between February 1989 and August 1990, all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results-Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent clandication (hazard ratio [WR], 1.9; 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0; 95% CI, 1.3 to 3.0), previous transient ischemic attack (HR, 2.4; 95% CT, 1.3 to 4.1), and prestroke Barthel Index <20/20 (HR, 2.0, 95% CI, 1.3 to 3.2). Conclusions-One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.

Overseas visitors admitted to Queensland hospitals for water-related injuries

Objective: To determine the number of overseas visitors admitted to Queensland hospitals for water-related injuries over three years, the causes of their injuries, the resulting conditions treated, and the type of hospitals to which they were admitted. Design: Retrospective analysis of admissions of overseas visitors to Queensland hospitals over the three financial years 1995/96, 1996/97 and 1997/98. Patients: 296 overseas visitors admitted for water-related injuries, identified from hospital records by their usual place of residence. Main outcome measures: Number of admissions, causes of injuries, conditions treated. and bed days occupied by these patients at different types of hospitals (metropolitan, regional and rural public hospitals, and private hospitals). Results: The 296 overseas visitors accounted for a total of 596 separate admissions, many of these the result of patients with decompression illness being admitted several times to a regional hospital hyperbaric chamber for treatment as day patients. The largest number of injuries involved the use of diving equipment. The main conditions treated were decompression illness (54.7%), fractures and dislocations (15.5%), and drowning and non-fatal submersion (14.9%). Overall, overseas visitors admitted to hospital following a water-related incident occupied 1215 bed days; 90% of these admissions were to regional hospitals. Conclusions: The main reason for admission of overseas visitors is for decompression illness, suggesting that the prevention of injuries among scuba divers requires further coordinated efforts by health and tourism authorities.

Investigation of threat-related attentional bias in anxious children using the startle eyeblink modification paradigm

We used the startle eyeblink modification paradigm to investigate whether clinically anxious children, like high trait-anxious adults, display a bias in favour of threat words compared to neutral words. The present study included 16 clinically anxious children whose diagnostic status was determined using the parent version of a semistructured diagnostic interview as part of a larger childhood anxiety study. The children were presented with threat and neutral words fur 6 s each. A startle-eliciting auditory stimulus - a 100 dBA burst of white noise of 50 ms duration - was presented during the words at lead intervals of 60, 120, 240, or 3500 ms and during intertrial intervals. The overall pattern of startle eyeblink modification indicated inhibition at the 120 and 240 ms lead intervals and facilitation at the 3500 ms lead interval. startle-latency shortening during threat words at the :60 ms lead interval was larger than at other intervals, whereas there was no difference during neutral words. This result reflects an anxiety-related bias in favour of threat words occurring at a very early - and possibly preattentive stage - of information processing.