Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP

The Clinical Global Impressions Scale (CGI) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder. Criticisms of the original CGI were addressed by correcting inconsistencies in scaling, identifying time frames for comparison, clarifying definitions of illness severity and change, and separating out assessment of treatment side effects from illness improvement during treatment. A Detailed User's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version (CGI-BP) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania, depression, and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis. Interrater reliability of the scale was demonstrated in preliminary analyses. Thus, the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder.     

Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans

Despite the association of increasing age with chronic wound-healing disorders and an impaired rate of healing of acute cutaneous wounds, the role of matrix metalloproteinases (MMPs) is unknown. To determine the spatial and temporal patterns and activities of MMP-1, -2, -3 and -9, 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 post-wounding. Wounds showed an age-related increase in MMP-2 and MMP-9 immunostaining from day 3; this was associated with degradation of gelatin as shown by zymograms and with increased proteinase activity as shown by azocoll assays. Distinct spatial localisations for each MMP were observed: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymography and increased MMP-2 immunostaining. These results indicate that: (1) intrinsic ageing is associated with the up-regulation of MMPs previously associated with chronic wound healing; (2) wound-tissue proteinases are essentially active up to day 21 postwounding; and (3) intrinsic ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.     

Production of enterotoxins by Bacteroids fragilis strains--effect of clindamycin

Four B. fragilis strains were examined: one nonenterotoxigenic (NTBF) and three producing enterotoxin (ETBF). The growth of cultures was determined and enterotoxin, which is released to the culture medium during growth of strains, was detected. BHI broth and BHI broth with addition of subinhibitory doses (sub-MIC) of clindamycin were applied. Bacterial cultures were incubated at 37 degrees C for 48 hours. After 4, 8, 16, 24, 48 hours of cultivation, samples of bacterial cultures were collected and the optical density was measured. Then the samples were centrifuged, supernatants were filtered through 0.45 micron filters and concentrated three times with 5000 D ultrafilters. Prepared samples were kept frozen at -70 degrees C until used. The titre of enterotoxin in samples was determined on human colon adenocarcinoma cell line HT 29/C1. Neutralization assay was performed with culture filtrates, which were enterotoxin-positive and with rabbit anti-enterotoxin serum. The results of the experiments indicate that enterotoxin is detected after 16 hours of incubation of ETBF strains. Clindamycin at subinhibitory concentrations (sub-MIC) inhibits the growth of B. fragilis cultures. The antibiotic causes also delay and decrease in enterotoxin production by ETBF strains.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

The safer choices project: methodological issues in school-based health promotion intervention research

Randomized trials of school-based health promotion programs present unique design and analytical issues not widely discussed in the research literature. This article describes the Safer Choices study--a school-based program for prevention of HIV, other sexually transmitted diseases, and pregnancy--to illustrate critical methodological issues involved in large-scale, school-based intervention trials, particularly those evaluating interventions with a school-wide focus. The issues presented are: 1) comparability of the intervention and control groups even when few units are randomized; 2) factors that affect the decision to use a cohort or cross-sectional design; and 3) appropriate analysis strategy when the unit of randomization and intervention is at the school level, but observations are at the student level.     

Phase I and pharmacological study of CI-980, a novel synthetic antimicrotubule agent

CI-980 (NSC 613862) is one of a novel class of 1,2-dihydropyrido[3, 4-b]pyrazines that inhibits tubulin polymerization, presumably by binding to the colchicine binding site of tubulin. In a Phase I and pharmacological study, 16 patients with advanced solid neoplasms were treated with CI-980 on a continuous 72-h infusion schedule at doses ranging from 3.0-5.4 mg/m2/day every 3 weeks. High rates of central nervous system (CNS) toxicity and neutropenia occurred in both minimally and heavily pretreated patients who were treated with CI-980 doses above 3.75 mg/m2/day, which is the maximum tolerated dose and the recommended dose for additional evaluations. CNS effects, characterized by neurocortical, mood, and cerebellar manifestations, were generally observed toward the end of the infusion and immediately posttreatment and usually resolved within 48 h after the completion of treatment. Toxicity was mild to modest at the 3.75 mg/m2/day dose level. Neither clinical nor pharmacological risk factors that may predispose patients to the development of CNS effects were evident. Although no objective antineoplastic activity was observed in this Phase I study, CI-980 steady-state plasma concentrations achieved at the recommended dose of 3.75 mg/m2/day (mean +/- SE, 5.74 +/- 0.54 nM) approached and exceeded concentrations that have been associated with significant activity in preclinical studies, indicating that additional disease-directed evaluations of CI-980 may be warranted.