Sodium channel block by a potent, new antiarrhythmic agent, transcainide, in guinea pig ventricular myocytes

Transcainide is a new lidocaine analog that has been shown to suppress a range of cardiac arrhythmias in an initial clinical trial. We have evaluated the effects of transcainide on sodium channel current in guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Reduction of sodium current by transcainide was concentration dependent, with an ED50 of approximately 0.5 microM (n = 9). This reduction of the sodium current exhibited little use dependence, and block did not accumulate even after 10-Hz pulse trains. Moreover, little or no recovery from block was observed even when cells were hyperpolarized to -160 mV for 1 min. We observed no reversal of sodium channel block after superfusing cells up to 1 h in drug-free solution. Thus, transcainide, unlike many other clinically useful antiarrhythmic agents, blocked sodium channels with very little time dependence or voltage dependence. These novel electrophysiological properties of transcainide may endow the agent with a unique spectrum of efficacy against certain arrhythmias. At the same time, the great potency of transcainide and its lack of reversibility, at least within an hour, mandate that the drug should be used with great caution.     

Performance measures for evaluating services for people with a first episode of psychosis

Aim: The purpose of this project was to operationalize and apply a previously identified set of performance measures designed to evaluate services for those experiencing a first episode of a schizophrenia spectrum disorder. Methods: Operational definitions were developed for previously identified measures through an iterative process of discussions between clinical experts and health‐care evaluators. Data were collected from existing sources including corporate databases, clinical databases and chart review. Results: Definitions were developed for 44 measures covering seven of eight domains recommended for service level evaluation by the Canadian Institute for Health Information domains. Forty measures could be calculated. Conclusions: The measures represent a comprehensive set of performance measures suitable for the evaluation of services for people with a first‐episode psychosis. The measures could be used by other services in order to establish standards and norms for routine clinical practice.     

Heartburn and gastro-oesophageal reflux.

Heartburn is a readily recognised symptom which half the British population have experienced at some time, and a fifth have frequently. It is the predominant symptom of gastro-oesophageal reflux, although less than two thirds of sufferers have endoscopically visible oesophagitis. Heartburn can also be associated with peptic ulcers or functional dyspepsia. Several changes in oesophageal function contribute to the syndrome of gastro-oesophageal reflux, the most important being inadequacy of the complex mechanism at the gastro-oesophageal junction. Understanding the various functional failures offers a better understanding of the therapeutic possibilities.     

To thin or not to thin: the use of the anterolateral thigh flap in the reconstruction of intraoral defects.

The anterolateral thigh (ALT) flap has achieved popularity recently for free-flap reconstruction of intraoral defects following excision of squamous cell carcinoma. We have assessed the feasibility of the ALT flap as a free flap for oral lining and the potential use of the thinned ALT flap in a one-stage reconstruction. We used the ALT flap to reconstruct the oral cavity in 18 consecutive patients between December 2000 and December 2001 following intraoral resection of squamous cell carcinoma. Twelve patients underwent reconstruction using a standard ALT flap, four patients received a thinned ALT flap in a one-stage procedure, one patient received a standard ALT flap in combination with a fibula flap and one patient received a combination of a standard ALT flap and vascularised iliac bone. There were no complications in any of the 14 cases in which a standard ALT flap was used. Two of these flaps were thinned subsequently as secondary procedures. Of the four thinned ALT flaps, one flap failed completely and two flaps experienced partial necrosis. In all but one case the donor site was closed directly with minimal donor-site morbidity. The ALT flap is a versatile flap that can be used in combination with other flaps for more complex defects with minimal donor-site morbidity and is a useful alternative in the armamentarium of the head and neck surgeon. Thinning of the flap is best performed as a secondary procedure, should it be required.     

Heroin self-administration in rats under a progressive ratio schedule of reinforcement

Heroin self-administration behavior under a progressive ratio (PR) schedule of reinforcement was evaluated in rats. The schedule was designed to restrict drug intake, minimize opiate dependency, and quantify the number of responses emitted (final response ratio) in order to receive a limited number of heroin infusions. Final ratios were found to be stable and did not increase with chronic (31 days) PR reinforcement. The ability of the PR schedule to detect changes in heroin reinforcement was demonstrated by evaluating the effect of naltrexone pretreatment and unit dose alteration on final ratios. Naltrexone (0.4 mg/kg) reduced final ratios and an inverted U dose-response relationship was established for the unit heroin doses 12.5–100 µg/injection. Maximal final ratios occurred with 50 µg/injection heroin reinforcement. This PR schedule may provide a useful method for evaluating the effects of pharmacological manipulations or lesions on opiate reinforcement.     

Intrauterine position affects motoneuron number and muscle size in a sexually dimorphic neuromuscular system

The intrauterine position occupied by a rodent fetus influences the amount of testosterone to which it is exposed before birth. Animals that are gestated between two male fetuses (2M) are exposed to higher circulating levels of testosterone than are animals positioned between two female fetuses (2F) and there are reliable differences in the reproductive physiology and behavior of 2M and 2F animals when adult. To determine whether intrauterine position modifies development of the central nervous system, we examined the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) in male and female gerbils from known intrauterine positions. We found that adult 2M female gerbils had 16% more SNB motoneurons than did 2F females. 2M males did not differ from 2F males in SNB motoneuron number, but the bulbocavernosus muscle, which is innervated by SNB motoneurons, was approximately 50% larger in 2M than in 2F males. These data indicate that intrauterine position can influence the morphology of the sexually dimorphic SNB neuromuscular system.     

Health insurance and private providers: A study of the civil servants' medical benefit scheme in bangkok,Thailand

Compulsory health insurance schemes have received attention recently as a means of creating a reliable extra-budgetary source of health care funding. Yet, the full implications of such schemes in a developing country context are unclear; in particular, the impact on and relationship with private sector providers has infrequently been explored. This study examines patterns of public and private sector utilization under the Civil Servants' Medical Benefit Scheme (CSMBS) in Bangkok, Thailand. The CSMBS currently provides limited reimbursement for private inpatient care, but recent proposals suggest increasing benefit levels for care sought in the private sector. The study shows that despite high level of cost recovery in the public sector, charges were much lower than those in the private sector. Different patterns of diagnosis in the two sectors were found with private hospitals tending to treat a less complex case mix. Within the private sector, there was a limited tendency to specialize in certain types of care. It is concluded that under the current payment mechanism of fee-for-service reimbursement, measures to enhance access to private sector care should be approached with caution. In the long run, the scheme should merge with the recently established social security scheme.     

Psychiatric morbidity among people aged 85+ in 1987. A follow-up study at two and a half years: Associations with changes in psychiatric morbidity

This article reports findings from a longitudinal survey of very elderly people living at home in London. The research aimed to identify social, psychological and physical characteristics associated with positive ageing and successful survival in the community in later life and its converse—negative ageing—as well as the associated policy implications. Associations with psychiatric morbidity, measured using the General Health Questionnaire, among sample members without cognitive impairment between the baseline interviews in 1987 and at follow-up, two and a half years later in 1990, are reported. Twenty-five per cent of survivors scored over the threshold of the GHQ in 1987 and 30% scored over the threshold in 1990. Half of those with a score over the threshold in 1990 also scored over the threshold in 1987. Hierarchical regression (using residualized change analysis) was used to estimate the effects of the independent variables on changes in psychiatric morbidity. The most significant predictor of psychiatric morbidity (GHQ score) in 1990 was baseline GHQ score, followed by health and functional status scores. Health and functional status were also the strongest predictors of baseline (1987) GHQ scores. The uniqueness of the study lies in the collection of follow-up data on a sample of very elderly people, given that most surveys are corss-sectional and contain too few people aged 85+ to merit separate analysis. It contributes to the small body of literature on outcome of depression. The lack of consistent associations with recovery from psychiatric morbidity in the literature enhances the importance of studies aiming to identify factors associated with different outcomes.