Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer. A cost-effectiveness analysis.

BACKGROUND: Aspirin may decrease colorectal cancer incidence, but its role as an adjunct to or substitute for screening has not been evaluated. OBJECTIVE: To examine the potential cost-effectiveness of aspirin chemoprophylaxis in relation to screening. DESIGN: Markov model. DATA SOURCES: Literature on colorectal cancer epidemiology, screening, costs, and aspirin chemoprevention (1980-1999). TARGET POPULATION: General U.S. population. TIME HORIZON: 50 to 80 years of age. PERSPECTIVE: Third-party payer. INTERVENTION: Aspirin therapy in patients screened with sigmoidoscopy every 5 years and fecal occult blood testing every year (FS/FOBT) or colonoscopy every 10 years (COLO). OUTCOME MEASURES: Discounted cost per life-year gained. RESULTS OF BASE-CASE ANALYSIS: When a 30% reduction in colorectal cancer risk was assumed, aspirin increased costs and decreased life-years because of related complications as an adjunct to FS/FOBT and cost $149 161 per life-year gained as an adjunct to COLO. In patients already taking aspirin, screening with FS/FOBT or COLO cost less than $31 000 per life-year gained. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness estimates depended highly on the magnitude of colorectal cancer risk reduction with aspirin, aspirin-related complication rates, and the screening adherence rate in the population. However, when the model's inputs were varied over wide ranges, aspirin chemoprophylaxis remained generally non-cost-effective for patients who adhere to screening. CONCLUSIONS: In patients undergoing colorectal cancer screening, aspirin use should not be based on potential chemoprevention. Aspirin chemoprophylaxis alone cannot be considered a substitute for colorectal cancer screening. Public policy should focus on improving screening adherence, even in patients who are already taking aspirin.

Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol).

8,24-Euphadien-3 beta-ol (euphol) on i.v. administration was found to exhibit a hypotensive activity in normotensive anesthetised dogs and rats which varied from a slight to a marked degree depending upon the dose range. Euphol inhibited various autonomic pressor and depressor responses. The hypotensive effect was not affected in dogs pretreated with atropine, antistine, and beta-blockers and in bilaterally vagotomised and carotid sinus denervated animals. The fall in blood pressure was enhanced in spinal transected and eviscerated dogs and after ganglion blockade with hexamethonium. Localisation of euphol to central cardiovascular loci displayed no effect on blood pressure. The LD50 in mice was found to be 1500 mg/kg i.p. and greater than 2 g/kg by the oral route.

Introduction of a Micrococcus plasmid in Escherichia coli.

A 6-MDa plasmid (pMQV10), carrying cholesterol hydroxylase and streptomycin-resistance genes, from a gram-positive strain of Micrococcus sps., (RJ6) has been successfully transformed in gram-negative Escherichia coli K12 C600. pMQV10 is maintained stably and expresses its drug resistance in the new host.

A fast spheroplast formation procedure in some 2,5-diketo-D-gluconate- and 2-keto-L-gulonate- producing bacteria.

Calcium 2-keto-L-gulonate (Ca-2-KLG, a key intermediate in vitamin C synthesis) is produced from calcium 2,5-diketo D-gluconate (Ca-2,5-DKG) by a variety of bacteria. A few bacterial species which efficiently convert glucose to Ca-2,5-DKG have been isolated in our laboratory. Our bacterial collection included species that possess the genes for production of Ca-2-KLG from Ca-2,5-DKG; however, the yield of the former is poor. A procedure for the preparation of spheroplasts in Ca-2,5-DKG- and Ca-2-KLG-producing bacteria was developed for the construction of recombinants (fusants), combining the genes for conversion of glucose to Ca-2-KLG efficiently by protoplast fusion. The standard procedure for spheroplast formation in Gram negative bacteria by the Tris-sucrose-EDTA-lysozyme system did not work in the organisms under investigation. The need for an alternative method was necessary. Our results show that, while the Tris-NaCl-EDTA-lysozyme system (pH 8.3) worked very well with bacterial strains of Gluconobacter oxydans (ATCC9937) and Acetobacter melanogenus (NCIM2259), the Tris-sucrose-EDTA-lysozyme system worked well for Erwinia herbicola (ATCC21998), Pseudomonas chlororaphis (NCIM2041) and Corynebacterium species (ATCC31090). However, none of these systems produced spheroplasts in Brevibacterium ketosoreductum (ATCC21914), for which a separate system is under development.

Hepatoprotective effects of Wedelia calendulacea.

The alcoholic extract of whole plant Wedelia calendulacea exhibited protective activity against carbon tetrachloride-induced liver injury in vivo. The extract also increased the bile flow in rats suggesting a stimulation of liver secretory capacity. The minimum lethal dose was greater than 200 mg/kg p.o. in mice.

Adaptogenic activity of seeds of trichopus zeylanicus gaertn, the ginseng of kerala.

The alchoholic extract of seeds of Trichopus zeylanicus showed a potent adaptogenic or antistress properties against a variety of stresses in both rats an dmice. The extract increased the swimming performance of normal and adrenalectomized mice. Significantly; prevented a variety of stress and chemical induced ulcerations in rats and also prevented milk-induced leucocytosis in mice. The extract further reduced the gastric secretary clume, PH and acid output in pylorusligated rat stomach. No mortalitiy was observed upto a dose of 3 g/kg per oral in mice. The study indicated that trichopus zeylanicus seeds induce a state of nonspecific increased resistance against a variety of stress induced biological changes in animals.

An economical large-scale procedure to purify Micrococcus plasmid DNA.

A reproducible and economical procedure for obtaining a large yield of highly purified covalently closed circular (ccc) plasmid DNA from an industrially important strain of Micrococcus is described. The procedure adopted here departs in several ways from commonly used protocols for isolation of plasmid DNA from Gram (positive) and Gram (negative) bacteria. The plasmid DNA prepared by this procedure is free of contaminants and is pure enough to be used for electron microscopy, DNA transformation, sequencing, in vitro transcription and mutagenesis.