Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic receptors: effects on the course of Alzheimer's disease.

Despite the proven efficacy of acetylcholinesterase inhibitors in Alzheimer's disease, there is a need for new and more effective treatments. Galantamine is a novel treatment for Alzheimer's disease that inhibits acetylcholinesterase and modulates nicotinic receptors. In randomized, double-blind, placebo-controlled studies of up to 6 months duration, galantamine significantly improved cognitive function. Galantamine also had beneficial effects on instrumental and basic activities of daily living, and postponed the progression of behavioral symptoms. Patients who completed one of the 6-month, placebo-controlled studies were eligible to enter a 6-month, open-extension study of the 24-mg/day dose of galantamine. At the end of 12 months, cognitive function and activities of daily living were preserved in those patients who had been treated throughout the study with galantamine 24 mg/day. At 12 months, this group of patients had significantly better cognitive functions than patients who had been treated with a placebo for 6 months before receiving galantamine. These studies indicate that galantamine postpones the progression of symptoms in Alzheimer's disease. Since galantamine shows the greatest benefits when treatment is started early, its long-term benefits may result from an effect on the underlying disease process; such an effect might be mediated by galantamine's concomitant action on nicotinic receptors.

Pseudallescheria boydii infection of the central nervous system.

Pseudallescheria boydii is a rare cause of central nervous system infection characteristically presenting as a neutrophilic meningitis or multiple brain abscesses. Factors predisposing to central nervous system infection with this fungus include immunosuppression and near drowning. The organism is infrequently cultured from fluid obtained by lumbar puncture, delaying clinical recognition and appropriate antifungal therapy. All untreated patients with P boydii infection of the central nervous system died. We describe a patient who developed a persistent neutrophilic meningitis with focal neurologic deficits due to P boydii 6 months after a freshwater aspiration pneumonia. We also review the characteristic clinical and pathologic features of previously reported cases and emphasize the importance of early detection and treatment in the management of this frequently intractable disease.

A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.

OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. METHODS: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. RESULTS: After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild. CONCLUSIONS: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Continuing contamination of north Atlantic and Arctic waters by Sellafield radionuclides.

Discharges of 99Tc and 129I from the reprocessing plant at Sellafield have increased significantly since the mid-1990s, against the overall trend of most other radionuclides. The 'pulsed' release of 99Tc has provided an opportunity to study transport pathways and transit times in UK waters, the North Sea and beyond. Transit times estimated from the 99Tc data are signifcantly shorter than rates reported previously using other radiotracers. The possible reasons for this are discussed. A comparison is made between the response of seawater concentrations and those in the brown seaweed Fucus vesiculosus to variations in the release rates. Current discharges of plutonium are very low compared with the 1970s and 1980s. However, the seabed sediments of the Irish Sea represent a substantial source and remobilisation into the water column results in the continuing export of plutonium from the Irish Sea and its transport to Arctic waters.

Alpha-emitting, hot particles in Irish sea sediments.

Alpha-emitting, hot particles have been observed in samples of liquid effluent from the nuclear fuel reprocessing plant at Sellafield, U.K. Similar particles, thought to originate from Sellafield, have been found in environmental samples from sites near the plant. The occurrence and distribution of hot particles in surface sediments from the northeastern sector of the Irish Sea are described and the implications for predicting transuranium element behaviour are discussed.

Geochemical fractionation of plutonium in anoxic Irish Sea sediments using an optimised sequential extraction protocol.

An optimised five-step sequential extraction protocol, incorporating the use of sodium citrate to inhibit resorption, has been used to assess the solid partition of plutonium under anoxic conditions in intertidal sediments from the Ravenglass Estuary in the north-eastern Irish Sea. The data reveal that the plutonium is predominantly bound to geochemical phases targeted by the acido-soluble and the exchangeable extractants, indicating that a significant proportion of the plutonium in these and similar sediments is associated with relatively mobile geochemical phases. The results are consistent with the relatively high level of plutonium remobilisation now known to be taking place throughout the north-eastern Irish Sea.