(1/1580) Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants.
Transcutaneous immunization (TCI) is a new technique that uses the application of vaccine antigens in a solution on the skin to induce potent antibody responses without systemic or local toxicity. We have previously shown that cholera toxin (CT), a potent adjuvant for oral and nasal immunization, can induce both serum and mucosal immunoglobulin G (IgG) and IgA and protect against toxin-mediated mucosal disease when administered by the transcutaneous route. Additionally, CT acts as an adjuvant for coadministered antigens such as tetanus and diphtheria toxoids when applied to the skin. CT, a member of the bacterial ADP-ribosylating exotoxin (bARE) family, is most potent as an adjuvant when the A-B subunits are present and functional. We now show that TCI induces secondary antibody responses to coadministered antigens as well as to CT in response to boosting immunizations. IgG antibodies to coadministered antigens were also found in the stools and lung washes of immunized mice, suggesting that TCI may target mucosal pathogens. Mice immunized by the transcutaneous route with tetanus fragment C and CT developed anti-tetanus toxoid antibodies and were protected against systemic tetanus toxin challenge. We also show that bAREs, similarly organized as A-B subunits, as well as the B subunit of CT alone, induced antibody responses to themselves when given via TCI. Thus, TCI appears to induce potent, protective immune responses to both systemic and mucosal challenge and offers significant potential practical advantages for vaccine delivery. (+info)
(2/1580) A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.
BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant. (+info)
(3/1580) Extraction and analysis of cosmetic active ingredients from an anti-cellulitis transdermal delivery system by high-performance liquid chromatography.
A new transdermal delivery system that controls cellulitis is evaluated using reversed-phase high-performance liquid chromatography coupled with photodiode array detection. An extraction procedure and the validation of the analytical method to assay the active excipients from the Centella asiatica plant (asiaticoside, madacessic acid, and asiatic acid) are described. Excellent results ae obtained in terms of linearity, accuracy, and specificity of the analytical method. (+info)
(4/1580) Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.
The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates. (+info)
(5/1580) Topical psoriasis therapy.
Psoriasis is a common dermatosis, affecting from 1 to 3 percent of the population. Until recently, the mainstays of topical therapy have been corticosteroids, tars, anthralins and keratolytics. Recently, however, vitamin D analogs, a new anthralin preparation and topical retinoids have expanded physicians' therapeutic armamentarium. These new topical therapies offer increased hope and convenience to the large patient population with psoriasis. (+info)
(6/1580) A successful tobacco cessation program led by primary care nurses in a managed care setting.
We conducted a descriptive study of a tobacco cessation program sponsored by a health maintenance organization (HMO) and led by primary care nurses. The tobacco cessation program was conducted at 20 primary care clinics in northeastern and central Pennsylvania. We gauged the successfulness of the program by the patients' self-reported quit rates at 1 year. We also examined the association between quit rates and compliance with scheduled counseling visits, the impact of the availability of an HMO pharmacy benefit that supported the costs of nicotine replacement therapy, and the quit rates among patients with HMO insurance versus those with insurance other than managed care. Of 1,695 patients enrolled in the program from July 1993 to March 1996, 1,140 completed 1 year of follow-up. Of these, 348 (30.5%) reported they had quit using tobacco. Among the 810 HMO enrollees who participated in the program, the quit rate was 280 (34.6%); among the 330 non-HMO participants, the quit rate was 69 (20.9%), a statistically significant difference (P < 0.001). For all patients, keeping more than four visits with the program nurse was associated with a significantly higher likelihood of quitting (317/751 [42.2%] versus 32/389 [8.2%]; P < 0.001). Non-HMO patients were less likely than HMO enrollees to keep four or more visits (165 [50%] versus 586 [72.3%]; P < 0.001). We were unable to detect a difference in quit rates among those with and those without a pharmacy benefit (196/577 [34%] versus 84/233 [36.1%]). These data are limited by their descriptive nature and the lack of information about other factors important in determining the quit rate among program participants. Nevertheless, they suggest that HMOs can successfully sponsor nurse-led tobacco cessation programs in multiple primary care settings and achieve 1-year quit rates significantly higher than the 15% quit rate reported in the medical literature. In addition, successfully quitting tobacco use appeared to be associated with use of counseling visits but not with use of a pharmacy benefit to pay for nicotine replacement therapy. Even though tobacco cessation programs have the best chance of benefitting HMO enrollees, patients not enrolled in managed care plans also appear to benefit significantly. This finding has important implications for developing future strategies--including the role of managed care organizations, the need to defray the costs of nicotine replacement therapy, and the best approach to provide counseling to patients--to meet the Healthy People 2000 goal of reducing tobacco smoking. (+info)
(7/1580) The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects.
AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. METHODS: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function. (+info)
(8/1580) Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial.
OBJECTIVE: To assess the efficacy and safety of low dose adrenaline injected subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum in patients admitted to hospital after snake bite. DESIGN: Prospective, double blind, randomised, placebo controlled trial. SETTING: District general hospital in Sri Lanka. SUBJECTS: 105 patients with signs of envenomation after snake bite, randomised to receive either adrenaline (cases) or placebo (controls) immediately before infusion of antivenom serum. INTERVENTIONS: Adrenaline 0.25 ml (1:1000). MAIN OUTCOME MEASURES: Development of acute adverse reactions to serum and side effects attributable to adrenaline. RESULTS: 56 patients (cases) received adrenaline and 49 (controls) received placebo as pretreatment. Six (11%) adrenaline patients and 21 (43%) control patients developed acute adverse reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse reactions to serum were also seen in the adrenaline patients for each category of mild, moderate, and severe reactions. There were no significant adverse effects attributable to adrenaline. CONCLUSIONS: Use of 0.25 ml of 1:1000 adrenaline given subcutaneously immediately before administration of antivenom serum to patients with envenomation after snake bite reduces the incidence of acute adverse reactions to serum. (+info)