Determination of diquat and paraquat in water by liquid chromatography-(electrospray ionization) mass spectrometry.

A method for the determination of the herbicides diquat and paraquat in water was developed using liquid chromatography-(electrospray ionization) mass spectrometry [LC-(ESI)MS]. The analytes were isolated on an ENVI-8 DSK solid phase extraction (SPE) disk and eluted with 5-M trifluoroacetic acid (TFA). The eluate was evaporated to dryness and the analytes were redissolved in the mobile phase (7% methanol/93% water/25-mM TFA). The extract was analyzed by liquid chromatography (C1 column) with postcolumn addition of propionic acid/methanol followed by (ESI)MS. Diquat was detected using the [M(2+)-H+] ion (M2+ = dication) at m/z 183, whereas paraquat was detected using the mono-trifluoroacetate ion pair [M2 +/- OOCCF3] at m/z 299. Quantitation was done by isotope dilution mass spectrometry using d4-diquat and d8-paraquat and the corresponding ions [M(2+)-D+] and [M2 +/- OOCCF3] at m/z 186 and m/z 307, respectively. Detection limits of 0.1 and 0.2 microgram/L, respectively (based on the dications), were adequate to meet the Ontario Drinking Water Objectives of 70 and 10 micrograms/L, respectively, and the Ontario Provincial Water Quality Objective for diquat of 0.5 microgram/L. Precision and accuracy were 14% and 6% for diquat and 12% and 3% for paraquat.

The aerospace screening electroencephalogram: an analysis of benefits and costs in the U.S. Air Force.

Using the techniques of decision analysis, three possible EEG screening strategies for U.S. Air Force pilots are evaluated. Available clinical and epidemiological data are organized so that the relative merits of the three strategies can be assessed by decision makers. The optimal strategy is found to be screening fighter pilot candidates only. Screening all pilot candidates is less "cost-effective" and using the EEG as a routine screening test in evaluating combat-qualified pilots for nonneurological conditions is the least effective strategy. Needs for further research and unanswered questions are discussed.

N-nitrosodimethylamine in drinking water using a rapid, solid-phase extraction method.

A simple, rapid method for the extraction of N-nitrosodimethylamine (NDMA) from drinking and surface waters was developed using Ambersorb 572. Development of an alternative method to classical liquid-liquid extraction techniques was necessary to handle the workload presented by implementation of a provincial guideline of 9 ppt for drinking water and a regulatory level of 200 ppt for effluents. A granular adsorbent, Ambersorb 572, was used to extract the NDMA from the water in the sample bottle. The NDMA was extracted from the Ambersorb 572 with dichloromethane in the autosampler vial. Method characteristics include a precision of 4 % for replicate analyses, an accuracy of 6 % at 10 ppt and a detection limit of 1.0 ppt NDMA in water. Comparative data between the Ambersorb 572 method and liquid-liquid extraction showed excellent agreement (average difference of 12 %). With the Ambersorb 572 method, dichloromethane use has been reduced by a factor of 1,000 and productivity has been increased by a factor of 3-4. Monitoring of a drinking water supply showed rapidly changing concentrations of NDMA from day to day.

Gepirone in the treatment of major depression.

Gepirone is a serotonin (5-hydroxytryptamine, 5-HT) type1A receptor agonist and a pharmacologic analogue of buspirone. Two double-blind, placebo-controlled studies show the efficacy of gepirone in the treatment of major depression. Study 1 demonstrates gepirone's superiority over placebo in an 8-week acute treatment of patients with major depression, including the melancholic subtype. Gepirone's antidepressant dose range is tentatively established at 5-30 mg/day. Study 2 reveals the benefit of gepirone compared with placebo in 4-week continuation therapy of patients with major depression who initially responded to 6 weeks of open therapy with gepirone. Analysis of Hamilton Rating Scale for Depression item scores show gepirone especially improves scores on items of core depression.

Gepirone treatment of atypical depression: preliminary evidence of serotonergic involvement.

This is a report of a controlled trial of gepirone, a 5-hydroxytryptamine (5-HT1A) partial agonist azapirone related to buspirone, in the treatment of atypical depression. The azapirones are of particular interest because their highly selective actions on the serotonergic system may possibly make them useful pharmacologic probes and potentially selective therapeutic agents. Sixty outpatients meeting Columbia criteria for definite or probable atypical depression were enrolled in a double-blind, randomized, placebo-controlled, 8-week clinical trial at a single site. The dosage schedule was fixed flexible, with 10-mg capsules given on a thrice-daily schedule, with doses of up to 120 mg daily. The response rate at 8 weeks for the intention-to-treat sample analyzed with the last observation carried forward was 62% (18 of 29 patients) for gepirone and 20% (6 of 30 patients) for placebo (chi 2 = 9.1; df = 1; p < 0.001). Robust and consistent drug-placebo differences are seen across virtually all rating scales post-treatment. The effect of gepirone was consistent across the levels of concomitant variables, including duration of episode and presence of dysthymia or panic. Gepirone is a novel antidepressant that holds promise for the treatment of atypical depression and that may be of heuristic value because of its relatively specific actions on the serotonergic system.

A pilot trial of gepirone vs. placebo in the treatment of cocaine dependency.

An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (greater than 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addiction Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI.

Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke.

OBJECTIVE: To test the hypothesis that intramuscular (IM) botulinum toxin type A (BTX) reduces excessive muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke. DESIGN: Randomized, double-blind, placebo-controlled, multicenter, 24-week trial. SETTING: Six academic and 13 private US outpatient medical centers. PARTICIPANTS: Ninety-one patients with a mean age of 60 years (range, 30-79 y). Mean time elapsed from ischemic or hemorrhagic stroke to study enrollment was 25.8 months (range, 0.9-226.9 mo). INTERVENTIONS: Up to 2 treatments of placebo, or 90, 180, or 360U of BTX. Concurrent splinting and physical therapy protocols were permitted, but no changes were allowed during the study. MAIN OUTCOME MEASURES: Wrist, elbow, and finger flexor tone assessed by the Modified Ashworth Scale, physician and patient global assessments, pain, FIM instrument, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Muscle tone decreased more with injections of BTX than with placebo in the wrist flexors at weeks 1, 2, 3, 6, and 9 (P< or =.026); in the elbow flexors at weeks 1, 2, 3, 4, 5, and 9 (P< or =.033); and in the finger flexors at weeks 1 and 3 (P< or =.031). A dose-dependent response was generally observed in tone reduction but not in pain, FIM, or SF-36 measures. CONCLUSIONS: IM BTX reduced muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke but did not appear to affect global quality of life or disability.