The NERC DataGrid services.

This short paper outlines the key components of the NERC DataGrid: a discovery service, a vocabulary service and a software stack deployed both centrally to provide a data discovery portal, and at data providers to provide local portals and data and metadata services.

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.

The efficacy of galantamine in the treatment of Alzheimer's disease: comparison of patients previously treated with acetylcholinesterase inhibitors to patients with no prior exposure.

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) can provide benefits at the cognitive, behavioral, and functional levels to patients with Alzheimer's disease (AD). With more AChEIs now available, treatment considerations may include whether the patient has had prior exposure to an AChEI. OBJECTIVE: To compare the effects of galantamine in patients with AD who were previously exposed to AChEIs with its effects in patients with AD who had no previous exposure, using a post hoc analysis. RESULTS: Patients in groups treated with galantamine 16 mg/day and 24 mg/day achieved statistically significant improvements in ADAS-cog/11 scores in comparison with those who received placebo (naive: p = 0.003 and 0.005, respectively; prior exposure: p < 0.001 and 0.001, respectively). Similarly, a greater number of patients treated with galantamine 16 mg/day and 24 mg/day exhibited no change or improvement in their CIBIC-plus scores compared to patients who received placebo (naive: p < 0.001 and p = 0.077, respectively; prior exposure: p = 0.005 and p = 0.001, respectively). There were no significant differences in adverse events between naive patients and those with prior exposure to AChEIs. CONCLUSIONS: Galantamine is effective and safe in patients with AD, regardless of previous exposure to AChEIs.

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.

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.

Disulfiram treatment of alcoholism.

To assess the efficacy of supervised disulfiram as an adjunct to out-patient treatment of alcoholics, a randomised, partially blind, six-month follow-up study was conducted in which 126 patients received 200 mg disulfiram or 100 mg vitamin C under the supervision of a nominated informant. In the opinion of the (blinded) independent assessor, patients on disulfiram increased average total abstinent days by 100 and patients on vitamin C by 69, thus enhancing by one-third this measure of treatment outcome. Mean weekly alcohol consumption was reduced by 162 units with disulfiram, compared with 105 units with vitamin C, and the disulfiram patients reduced their total six-month alcohol consumption by 2572 units compared with an average reduction of 1448 units in the vitamin C group. Serum gamma-GT showed a mean fall of 21 IU/I in patients on disulfiram but rose by a mean of 13 IU/I with vitamin C. Unwanted effects in the disulfiram group led to a dose reduction in seven patients and to treatment withdrawal in four (and in one vitamin C patient). Two-thirds of the disulfiram group asked to continue the treatment at the end of the study. There were no medically serious adverse reactions.

Alcohol problems among women in a general hospital ward.

This paper reports a study which was conducted to establish the utility of a screening procedure consisting of a structured interview and blood tests (GGT and MCV) to detect early problem drinking in female patients in a short-stay general hospital ward. The proportion of women identified by the interview schedule was found to be greater than has been reported in general practice and some other studies of female problem drinking. However, most of the blood tests were normal for this group. Excessive alcohol consumption was significantly associated with attempted suicide by drug overdose.

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.

The Scottish first episode schizophrenia study. VII. Two-year follow-up. Scottish Schizophrenia Research Group.

Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms.

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.

Plutonium redistribution by biological activity in Irish Sea sediments.

As part of a programme investigating the fate of transuranium nuclides discharged to coastal waters we have studied the effects of benthic animals on plutonium redistribution in Irish Sea sediments. From analyses of burrow linings of the large echiuroid Maxmulleria lankesteri, which penetrates to depths exceeding 40 cm, we now show that this animal may have a significant effect on the removal of plutonium to deeper layers in the sea bed.

A quantitative analysis of ultrastructural changes induced by electrical stimulation of identified spinal cord axons in the larval lamprey.

Microelectrodes filled with horseradish peroxidase (HRP) were used to label single identified giant axons in the isolated lamprey spinal cord. Subsequent to the iontophoretic injection of HRP, the spinal cord was stimulated at repetition rates of 20-30/s and the activity in labelled axons monitored. Immediately following failure of the action potential, the spinal cord was fixed by immersion and processed for light and electron microscopy. Electron micrographs were taken of synaptic contacts made by the labelled axons. Several quantitative measures were made from each synapse using a digitizing tablet interfaced with a digital computer. These measures included vesicle number (VN), vesicle area (VA), length of differentiated membrane (DM), vesicle density (VD = VN/VA), vesicle frequency (VF = VN/DM), and a relative measure of the amount of vesicle membrane added to the axolemma during the stimulation period, the curvature ratio (CR). Measures from 106 stimulated synapses were compared with 134 synapses from injected but unstimulated giant axons. The results from these experiments suggest that measurable ultrastructural changes occur during transmitter release at identified C.N.S. synapses, which are consistent with the hypothesis of synaptic vesicle recycling.

Epidemiological investigation of patients with vulvovaginal candidosis. Application of a resistogram method for strain differentiation of Candida albicans.

The resistogram method was applied to 420 isolates of Candida albicans obtained from 30 selected patients undergoing treatment for vulvovaginitis. Of these, 16 patients each harboured a particular strain of C. albicans which persisted in the mouth or intestinal tract or both. In three of these patients, this strain persisted in the genital tract, and, in eight patients, it later recolonised the genital tract. Fourteen patients harboured more than one strain of C. albicans: one failed to respond to treatment and continued to harbour the same strain in the genital tract; in five the original strain later recolonised the genital tract and a second strain remained confined to the mouth or intestinal tract or both; and in three a second strain, present in the intestinal tract, later colonised the genital tract. Each of the male partners of seven patients harboured a strain of C. albicans that was identical to the strain, or to one of the strains, that had been isolated from his female partner.