NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese-diabetic ob/ob mice

Quantitative autoradiography was used to characterise the binding of selective radiolabelled antagonists for the N-methyl-D-aspartate (NMDA) receptor and the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor in the dorsal, intermediate and ventral subregions of the grey matter of the upper thoracic spinal cord in male and female lean and obese-diabetic (ob/ob) mice. The density of binding sites for both receptor subtypes was greater in diabetic mice, in all three subregions of the grey matter, than the corresponding subregions in the lean mice. The affinity of the binding site for the NMDA antagonist was significantly higher in obese mice than lean mice, consistent with the presence of two subpopulations of NMDA receptors with different ligand binding affinities in obese mice. The increase in expression of the glutamate receptor subtypes, and altered ligand affinity for the NMDA receptor subtype in the obese mice may be causally involved in the peripheral neuropathies which can accompany diabetes mellitus.     

Health status of juvenile offenders. A survey of young offenders appearing before the juvenile courts

This paper reports on the health needs of a sample of juvenile offenders appearing before a Manchester Court during the month of August 1992. Of the 192 subjects interviewed (74% of those listed), 19% had significant medical problems, 42% a history of substance abuse and 7% psychiatric problems requiring further treatment. Substantial numbers (26%) engaged in a variety of dangerous behaviours. Custodial remands were common (21%), particularly in those with multiple psychosocial difficulties.     

Therapeutic Agents of Assertive Community Treatment

The goal of this study was to learn how assertive community treatment (ACT) contributes to the improvement of those with serious mental illness in order to contribute to the growing clinical literature regarding the therapeutic agents of ACT teams. Methods included reviewing the case records of three ACT clients who have improved significantly, as well as interviewing the clients themselves and their clinicians. The results indicated that there was significant agreement among the case records, the clients, and their clinicians in identifying the most useful aspects of assertive community treatment. Primary among these factors were the persistence demonstrated by ACT clinicians in engaging their clients, the trust that clients developed in their clinicians, and as a result, the process by which their clinicians became guides to the world of psychiatric and social services that further facilitated their clients' community adjustment. In closing, we consider implications from these findings both for staff development for ACT team members, and for suggestions toward the development of a model of recovery from serious mental illness.     

Avoiding malpractice in private practice and the hospital setting

An overview of very real considerations for the practicing plastic surgeon with regards to potential areas of risk and liability have been presented. As one can see, the hospital environment presents many potential sources of liability that can involve the attending or consulting plastic surgeon.     

Search for a gene x environment interaction: G x E hunt

We developed a method to identify gene x environment interactions (G x Es). To test this method in the simulated data (Problem 2, GAW11), we first identified an environmental factor (E1) that was associated with the simulated disorder. We stratified affected sibling pairs (ASPs) into two groups, those concordant for the presence of E1 and those concordant for the absence of E1. We then localized genes on chromosomes 3 and 5 using identity-by-descent (IBD) sharing rates among ASPs. Because the stratified IBD sharing rates are independent of the environmental factor if there is no G x E, we inferred the existence of a G x E near loci 3G44 and 3G45 by testing whether the proportion of ASPs sharing no alleles IBD differed among the two groups.     

The effects of idazoxan on reaction times, eye movements and the mood of healthy volunteers and patients with upper respiratory tract illnesses.

An experiment was carried out to determine whether idazoxan, a drug which increases the turnover of central noradrenaline, removes the malaise (reduced alertness, slower psychomotor performance) associated with upper respiratory tract illness (URTI). Eighty-one volunteers were tested when healthy and 17 returned to the laboratory when they developed URTIs. Those who remained healthy were then recalled as a control group. Volunteers were tested before and after receiving either idazoxan (40mg) or a lactose placebo. Idazoxan removed the URTI-induced slowing in a simple reaction time task and this group performed at a comparable level to the healthy group. No significant stimulant effect of idazoxan was found in the healthy subjects. The results suggest that at least part of the malaise induced by URTIs may reflect reductions in central noradrenaline and that this can be reversed by compounds such as idazoxan.     

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice.
2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice.
3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice.
4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice.
5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin.
6. The results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.

     

Sedative antidepressants impair visual detection mechanisms in humans

The safety of sedative antidepressants is a topical issue in the treatment of depression, with driving impairment being of particular concern. We have recently completed a study with normal male volunteers comparing the actions of dothiepin (a traditional, sedating antidepressant) with those of fluvoxamine (one of the selective serotonin re-uptake-inhibiting SSRI class of newer antidepressants) on psychomotor functions relevant to driving. We set out to investigate whether these drugs impair visual selective attention (focused and divided) by employing the 'odd-ball' task. Subjects were required to respond to letters of the alphabet (T for target and other letters for non-targets) that were presented at the centre and/or periphery of the computer screen. The task has been shown to be useful in detecting differences between drugs in their effects on selective attention. Preliminary results show that dothiepin delayed responses to single targets compared with fluvoxamine and placebo. There was also preliminary evidence that it mainly affected response times to peripheral targets. Furthermore, there was preliminary evidence that both drugs delayed responses to central targets compared with placebo on the divided attention trials. Finally, response accuracy in detecting peripheral targets was greater under placebo compared with fluvoxamine and dothiepin. The impairment produced by dothiepin is presumably a consequence of the central blockade of cholinergic muscarinic or histaminergic H1 receptors. It could contribute to the reported association between the tricyclic class of antidepressants and road traffic accidents, and would be worth further investigation in depressed patients taking both classes of drug.