Preclinical profile of stereoisomers of the anticonvulsant remacemide in mice

Stereoisomers of remacemide (racemate form) were compared for anticonvulsant efficacy and safety in mice. In the maximal electroshock seizure (MES) test for oral efficacy, the (-) stereoisomer, FPL 14145, was more potent than the racemate or the (+) stereoisomer, FPL 14144. Respective ED50 values (expressed as mg/kg) were: remacemide, 58; FPL 14145, 45; FPL 14144, 79. In 2 of 3 tests for neural impairment, FPL 14145 yielded significantly better therapeutic indices (toxic dose 50/ED50) than the racemate. The margin of safety (estimated median lethal dose ED50) was more favorable for FPL 14144: remacemide, 15.1; FPL 14144, 18.9; FPL 14145, 15.7. The duration of protection against MES indicated the stereoisomers were longer acting than the racemate. After intravenous administration the order of potency against MES was similar: FPL 14145 greater than remacemide greater than FPL 14144. Following daily administration of the oral ED98 for 4 days, with a dose response curve run on day 5, the MES ED50 values for all compounds were increased. The test indicates tolerance. In the pentylenetetrazol infusion test the racemate and FPL 14144 demonstrated more proconvulsant properties than FPL 14145. Intraperitoneal administration of 50 mg/kg or more produced changes in behavior with all compounds. At higher doses the racemate and FPL 14145 elicited more severe symptoms with death at 200 mg/kg.     

Transactional models of early education effectiveness - What is the message for policy?

There is now a substantial body of American research evidence demonstrating that early education programmes can have major long term effects right through into adult life. Cost-benefit analysis has enabled the data to be transformed into a compelling case for public financial investment. But insufficient attention has been paid to explaining how a short term preschool programme could have such enduring effects. The effects are best understood by applying a transactional model which shows how processes in the school and community transformed and amplified short term effects into long term outcomes. Adopting a transactional model modifies the messages for policy. The results of evaluations carried out in one society may not apply in another. In some school systems there may be more effective strategies than early education for improving educational prospects.     

Local anaesthesia for fibreoptic bronchoscopy: transcricoid injection or the "spray as you go" technique?

Local anaesthesia for fibreoptic bronchoscopy should be given by a safe technique that is not unpleasant to the patient and should provide acceptable conditions for the bronchoscopist. Single injection transcricoid local anaesthesia was compared with the "spray as you go" technique in patients having day case fibreoptic bronchoscopy. Patients were randomised to receive either 100 mg lignocaine by a single cricothyroid puncture or 240 mg lignocaine instilled through the bronchoscope under direct vision. Further doses were given by the operator to both groups as required. The 30 patients receiving transcricoid lignocaine coughed less (3.56 (SD 3.1) coughs/min) than the 32 patients receiving lignocaine through the bronchoscope (5.89 (4.8)/min) despite receiving a lower total dose of lignocaine (322 (25.9) v 451 (20.9) mg). Cricothyroid puncture was not associated with any complications and was not unpleasant for the patients.     

A national confidential enquiry into community acquired pneumonia deaths in young adults in England and Wales. British Thoracic Society Research Committee and Public Health Laboratory Service

BACKGROUND: The aim of this study was to describe the frequency, causal pathogens, management, and outcome of a population of young adults who died from community acquired pneumonia (CAP). METHODS: Pneumonia deaths in England and Wales in adults aged 15-44 were identified between September 1995 and August 1996. Patients with underlying chronic illness including HIV infection were excluded. Clinical details for each case were collected from the hospital and general practitioner records. RESULTS: Death from CAP was identified in 27 previously well young adults (1.2 per million population per year). Twenty were known to have consulted a GP for this illness. Nine received antibiotics before hospital admission. A causative pathogen was identified in 17 cases (Streptococcus pneumoniae in eight). Bacteraemia was present in seven. All patients who reached a hospital ward received antibiotics (69% within two hours of admission). The British Thoracic Society antibiotic guidelines for severe CAP were followed in only 10 cases. Cardiac arrest at home or on arrival at hospital occurred in six cases, one of whom was successfully resuscitated. Of the remaining 21 patients, 71% had two or more markers of severe CAP. All 22 who were admitted reached an intensive care unit, but 11 of these required transfer to another hospital for some aspect of intensive care. One third of patients died within 24 hours of presenting to the hospital. CONCLUSIONS: Death from CAP in previously fit young adults still occurs. While some deaths might be preventable by better patient management, most are unlikely to be preventable by current management practices.     

Aging changes in the heart of a poeciliid fish, the guppy Poecilia reticulatus

Histological surveys of the hearts of guppies Poecilia reticulatus throughout their lifespan showed no aging changes until the fish were three years old. In younger fishes the hearts were healthy, even in three individuals with “wasting” disease, where there was considerable loss of muscle throughout the body. There was a loss of muscle fibers in the ventricle in old fish, and deposition of collagen in the bulbus arteriosus. Guppies of three years and older also had a marked accumulation of melanomacrophages in the atrium. It seems unlikely that degeneration of the heart is involved in mortality of guppies in the wild.