What is the potential cost-effectiveness of enforcing a prohibition on the sale of tobacco to minors?

BACKGROUND: Enforcement programs to halt the sale of tobacco to youths have been implemented across the United States. The potential cost-effectiveness of enforcement was evaluated under a range of assumptions regarding cost and impact. METHODS: An enforcement model was constructed incorporating quarterly inspections of all tobacco vendors. The cost of discounted years of life saved was calculated using reported values regarding cost and a range of assumptions regarding the impact on youth tobacco use. RESULTS: Inspecting an estimated 543,000 tobacco outlets would cost up to $190 million annually. Costs range from $44 to $8,200 per year of life saved depending on the discount rate and assumptions regarding cost, and efficacy. To compete in cost-effectiveness with implementing smoking cessation guidelines, enforcement would have to produce a 5% reduction in adolescent smoking at a cost of no more than $250 per vendor. CONCLUSION: At this level of cost and effectiveness an enforcement program could save 10 times as many lives as the same amount spent on mammography or screening for colorectal carcinoma. A one-cent per pack cigarette tax could fully fund enforcement. Enforcement of tobacco sales laws deserves further study as one component of a multifaceted approach to tobacco use prevention.

The sales of lottery tickets to minors in Illinois.

Fifty retail outlets were tested with a 16-year-old girl in eight central Illinois cities to determine the willingness of retail clerks to illegally sell a lottery ticket to a minor. A total of 49 establishments or 98% sold. In two instances the youth was denied access to cigarettes but sold a lottery ticket despite the sales of both to a minor under age 18 being illegal in Illinois. A very low cost method of correcting the problem is presented.

[Studies of the effect of ischemia of the legs on the degree of osteoporosis of the femur and tibia using the cortex-shaft index]. / Badania nad wplywem przewleklego niedokrwienia konczyn dolnych na stopien osteoporozy kosci udowych i piszczelowych przy uzyciu wskaznika korowo-trzonowego.

On the basis of arteriographs in 98 patients with chronic arterial ischemia of lower limbs, degree of osteoporosis was determined in symmetrical femoral and tibial bones using cortical index and statistical calculations. The study demonstrates similar level of mineralization of the examined bones in limbs with similar degree of ischemia. In patients with more pronounced unilateral osteoporotic changes more severe obliterations of the arteries was observed in the respective limb as compared with the opposite limb. The observed differences in cortical index values are statistically significant. Moreover chronic ischemia diminishes the correlation between cortical index and age. The study indicates, that chronic bone ischemia could play a role in the pathomechanism of local osteoporosis.

Prevention of acute gastric mucosal lesions by Solcoseryl.

Solcoseryl, a deproteinized extract from calf blood containing various biologically active substances, has been reported to promote the healing of skin wounds and gastric ulceration In this study, the gastroprotective effects of Solcoseryl vis-a-vis acute gastric mucosal damage were examined in rats. Solcoseryl significantly reduced the formation of acute lesions induced by intragastric application of absolute ethanol or acidified taurocholate and by water immersion and restraint stress, but failed to affect those caused by acidified aspirin. Since Solcoseryl did not offer protection in the absence of mucosal prostaglandins (PG) e.g. in aspirin-induced gastric damage, it is likely that PG may be involved in the observed gastroprotective activity of the drug. Solcoseryl failed to affect gastric acid or pepsin secretion, but increased mucosal blood flow. Thus PG generated by Solcoseryl might contribute to the maintenance of the observed mucosal microcirculation and the prevention of lesion formation by corrosive substances and stress conditions.

Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins.

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.

Studies on the gastroprotective and ulcer-healing effects of colloidal bismuth subcitrate.

We investigated the gastroprotective effects of colloidal bismuth subcitrate (CBS, De-Nol) in comparison with agents such as sucralfate and methylated PGE2. Both CBS and sucralfate given orally prevented dose dependently the formation of gastric lesions by acidified aspirin, ethanol and restraint stress, CBS being more potent on a weight-to-weight basis than sucralfate. CBS and sucralfate were also equally effective in enhancing the healing rate of chronic gastric and duodenal ulcer induced by serosal application of acetic acid, while methylated PGE2 was completely ineffective in this model. Non-colloidal bismuth subnitrate, in contrast to CBS, was ineffective against stress-induced lesions. CBS stimulated mucosal generation and luminal release of PGE2 dose dependently.

Cytoprotective and ulcer healing properties of prostaglandin E2, colloidal bismuth and sucralfate in rats.

This study describes the model of chronic gastric and duodenal ulcerations induced by the application of acetic acid on a strictly defined area of the serosal surface of the stomach and duodenum for 10 and 20 s, respectively. Acetic acid applied for longer (20-60 s) or on a larger area (28-64 mm2) resulted in the formation of severe ulcerations which penetrated into the surrounding organs and had very prolonged healing time. Ulcers induced by the application of acetic acid for 10-20 s on a smaller area (7-13.8 mm2) healed spontaneously within 2-3 weeks, thus constituting a model suitable for evaluation of drugs affecting the process of ulcer healing. Our preliminary results of 7- to 14-day treatment with certain drugs indicate that sucralfate and De-Nol, at the dose which does not affect gastric acid secretion, accelerated the healing rate of both gastric and duodenal ulcers so that the observed ulcer healing effect could be attributed to their ulcer healing property. In contrast, 16, 16-dimethyl PGE2 (dmPGE2) in cytoprotective dose was completely ineffective in enhancing ulcer healing. Higher, gastric inhibitory dose of dmPGE2 accelerated the healing of duodenal but not gastric ulcerations, indicating that the inhibition of gastric secretion rather that cytoprotective activity is responsible for ulcer healing effect of this prostaglandin.

Gastric mucosal protection by agents altering gastric mucosal sulfhydryls. Role of endogenous prostaglandins.

Intragastric administration of sulfhydryl-containing cysteamine or sulfhydryl-oxidizing diethylmaleate caused a dose-dependent reduction in the mean area of gastric lesions induced by absolute ethanol. The protective effects of these agents are abolished by the sulfhydryl blocker N-ethylmaleimide, while indomethacin, a potent inhibitor of cyclooxygenase, caused only about 50% reduction in this protection. This study indicates that mucosal generation of prostaglandins contributes to the gastric cytoprotection by these agents administered intragastrically, but endogenous sulfhydryls are also involved in the gastric mucosal protection by sulfhydryl-containing or sulfhydryl-oxidizing compounds.

Gastric protection by meciadanol. A new synthetic flavonoid inhibiting histidine decarboxylase.

Flavonoids reportedly inhibit histidine decarboxylase and reduce gastric mucosal histamine content. We studied the effects of acute and chronic intragastric administration to rats of meciadanol, a new synthetic flavonoid (Zyma S.A., Nyon, Switzerland). The action of meciadanol was compared to that of 16,16-dimethyl PGE2. Meciadanol did not affect acid or pepsin output at any dose used. High doses of 16,16-dimethyl PGE2 reduced both acid and pepsin output. Meciadanol partially prevented aspirin-induced lesions but the prevention required chronic administration of meciadanol. In contrast, a single dose of meciadanol completely prevented ethanol-induced lesions. Chronic administration of meciadanol also completely prevented ethanol-induced lesions. 16,16-Dimethyl PGE2 prevented both aspirin-induced and ethanol-induced lesions in doses that did not affect acid or pepsin output. Meciadanol did not influence the effect that either aspirin or ethanol had on endogenous mucosal PGI2. Thus, the dose range of meciadanol that protected against ulcerogens did not affect either gastric acid secretion or pepsin output. Therefore, we conclude that meciadanol's action represents true cytoprotection, which was previously attributed only to prostaglandins.

Antiulcer and gastroprotective effects of solon, a synthetic flavonoid derivative of sophoradin. Role of endogenous prostaglandins.

Solon is a synthetic isoprenyl flavonoid derived from sophoradin which is isolated from the root of an ancient Chinese plant. Solon was administered orally or intraperitoneally to rats. It inhibited dose dependently gastric ulcers produced by acidified aspirin, water immersion and restraint stress. Solon was also gastroprotective for the stomach as it reduced dose dependently the gastric necrotic lesions induced by absolute ethanol given orally. The degree of gastroprotection decreased with time, the optimal effects occurring 60-90 min after oral administration. Pretreatment with indomethacin partly prevented the gastroprotective effects of Solon. When given alone to fasted rats, Solon increased dose dependently the mucosal content of prostaglandins (PG), suggesting that the protective effects of this drug may be mediated at least in part by endogenous PG.

Advances in the understanding of the mechanism of cytoprotective action by colloidal bismuth subcitrate.

This study was designed to compare the gastroprotective effects of colloidal bismuth subcitrate (CBS) with those of sucralfate and methylated analog of prostaglandin E2 (PGE2) against acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), and water immersion and restraint stress in rats. When given orally, both CBS and sucralfate prevented in a dose-dependent way the formation of gastric lesions induced by all three ulcerogens, CBS being about 7, 2, and 20 times more potent, respectively on a weight-to-weight basis than sucralfate. Methylated PGE2 was also highly effective against these ulcerogens. Bismuth subnitrate was ineffective against acute gastric lesions induced by stress conditions. The protection of both CBS and sucralfate was reversible when the animals were pretreated with indomethacin to suppress the generation of endogenous prostaglandins. Since CBS and sucralfate increased the production of PGE2 in the gastric mucosa, we postulate that their gastric protective action may be mediated, at least partly, by mucosal prostaglandins.

Comparison of gastric and intestinal antisecretory and protective effects of prostacyclin and its stable thia-imino-analogue (Hoe 892) in conscious rats.

The effects of prostacyclin (PGI2) and its stable thia-thimo-analogue (Hoe 892) on gastric and intestinal secretions and gastric mucosal lesions have been determined in conscious rats. Both PGI2 and Hoe 892 given subcutaneously (s.c.) reduced dose-dependent gastric acid secretion, the ID50 (dose producing 50% inhibition) being about 48.6 and 11.8 micrograms/kg, respectively. In contrast, intragastric (i.g.) PGI2 and Hoe 892 did not cause any change in gastric acid secretion at doses ranging from 1 to 100 micrograms/kg. Both PGI2 and Hoe 892 reduced significantly intestinal fluid secretion (antienteropooling activity). PGI2 and Hoe 892 given i.g. or s.c. reduced dose-dependent gastric ulcer formation induced by acidified aspirin (ASA), Hoe 892 being somewhat less potent than PGI2. Both PGI2 and Hoe 892 were equally effective against gastric mucosal necrosis induced by absolute ethanol and this effect was observed both after i.g. and s.c. administration of these agents. We conclude that stable thia-imino-PGI2 analogue, Hoe 892, has similar gastric and intestinal antisecretory and protective activity as PGI2 and may be useful in the prevention of gastric damage by various noxious agents.

Generation of endogenous prostaglandins and thromboxanes in taurocholate-induced gastric mucosal lesions.

This study demonstrates that the suppression of thromboxane biosynthesis by OKY-1581, a selective inhibitor of thromboxane biosynthesis, prevents dose-dependently taurocholate-induced gastric mucosal necrosis and enhances the cytoprotective effect of low dose of taurocholate against mucosal necrosis by large dose of this agent. In all animals treated with OKY-1581, a decrease in mucosal generation of thromboxane was accompanied by an increased production of PGs probably due to availability of greater amounts of a common substrate in a cyclooxygenase pathway. This study provides direct evidence that gastric mucosa generates thromboxanes which may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.

Role of prostaglandin and thromboxane biosynthesis in gastric necrosis produced by taurocholate and ethanol.

The effects of a new selective inhibitor of thromboxane biosynthesis, OKY-1581, and a potent inhibitor of cyclooxygenase, indomethacin, on gastric mucosal lesions induced by taurocholate or ethanol and mucosal generation of prostaglandins have been studied in rats. OKY-1581 prevented, dose dependently, the formation of taurocholate- but not ethanol-induced gastric necrosis, and this effect was accompanied by an increase in gastric mucosal generation of prostaglandin E2 and I2-like activity and a reduction in the thromboxane generation during platelet aggregation. OKY-1581 enhanced the cytoprotective action of "mild" irritants such as 5 mM taurocholate against gastric damage by 100 mM taurocholate, whereas indomethacin produced opposite effects. This study indicates: (1) the inhibition of thromboxane biosynthesis results in increased generation of prostaglandins which seems to contribute to the gastric mucosal integrity and, (2) thromboxanes may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.

Protective action of omeprazole, a benzimidazole derivative, on gastric mucosal damage by aspirin and ethanol in rats.

This study was designed to compare the influence of omeprazole, a potent inhibitor of H+/K+-ATP-ase involved in the final step of H+ secretion and prostaglandin (PG) I2 on the formation of gastric mucosal lesions induced by absolute ethanol or acidified aspirin (ASA). Omeprazole given intragastrically in both inhibitory (20 or 200 mumol/kg) and noninhibitory doses (2 mumol/kg) prevented dose dependently ASA- and ethanol-induced gastric lesions. The protective effect of omeprazole against ASA-induced lesions occurred when mucosal generation of PGs was completely suppressed and that against ethanol lesions when PG generation was increased above normal values. Pretreatment with PGI2 given intragastrically or subcutaneously both in inhibitory and noninhibitory doses prevented almost completely the formation of gastric mucosal lesions caused by both absolute ethanol and acidified ASA. This study indicates that omeprazole is capable of protecting gastric mucosa against ASA- and ethanol-induced injury and that this protection is unrelated to gastric inhibition or the biosynthesis of mucosal PGs.

Gastric cytoprotection by agents altering gastric mucosal sulfhydryl compounds: role of endogenous prostaglandins.

Intragastric administration of cysteamine or diethyl maleate caused a dose-dependent reduction in the mean area of gastric lesions induced by absolute ethanol but failed to affect gastric ulcerations produced by acidified aspirin. Mucosal levels of glutathione were increased with cysteamine and reduced with diethyl maleate and did not correlate with the protective action of these agents on ethanol-induced mucosal lesions. The protective effects of these agents probably involved mucosal generation of prostaglandins, because pretreatment with indomethacin or aspirin, potent inhibitors of cyclooxygenase, partially prevented this protection. This study indicates that the mucosal generation of prostaglandins contributed, at least in part, to the gastric cytoprotection by agents altering mucosal contents of sulfhydryl compounds.

Inhibition of gastric secretion by fat and hypertonic glucose in the dog: role of gastric inhibitory peptide.

1. The gastric and intestinal phases of gastric secretion were selectively evoked by 'meals' of 5% liver extract or saline in five dogs provided with a special cannula that allowed complete separation of the stomach from the duodenum. 2. The gastric phase in response to liver extract administered into the stomach amounted to an increase in acid output equivalent to about 70% of the maximum output in response to histamine. There was also a significant rise in the concentration of gastrin but not of gastric inhibitory peptide (GIP) in the serum. 3. The addition of fat (2 or 4% corn oil) or glucose (20%) to this liver extract meal inhibited secretion of gastric acid by 50 and 30%, respectively, without affecting the concentration of gastrin or GIP in the serum. 4. The 5% liver extract in the duodenum stimulated an increase in gastric acid output amounting to about 40% of the maximum response to histamine. Serum gastrin and GIP levels were not affected. Additional fat (0.5-4.0%) or glucose (10-20%) reduced acid secretion under these conditions by between 50 and 80% without affecting serum gastrin concentrations. Significant increases in the concentration of GIP in the serum occurred in response to intraduodenal glucose (5%), and to fat at the highest dose used (4%). 5. Intraduodenal infusions of glucose (5-20%) significantly increased serum GIP levels. Gastric secretion in response to 5% liver extract in the stomach was significantly inhibited at the highest dose (10 or 20%) although gastrin release was unaffected. 6. These results show that intraduodenal fat and glucose both exhibit potent inhibitory effects on post-prandial gastric acid secretion but that there is no correlation between the changes in serum GIP concentration and the inhibition of gastric secretion under these conditions. 7. We conclude that GIP is unlikely to mediate fat-induced inhibition of gastric secretion, but it is still possible that it might be involved in the inhibition that occurs during intestinal perfusion with hypertonic glucose solutions.

Gastric cytoprotection by acetazolamide: role of endogenous prostaglandins.

This study was designed to determine the influence of acetazolamide, a potent inhibitor of carbonic anhydrase, on the formation of gastric mucosal lesions induced by acidified aspirin (ASA) or absolute ethanol and on gastric cytoprotection induced by prostaglandin E2 (PGE2). Acetazolamide prevented dose-dependently ethanol-induced gastric lesions and this effect was accompanied by an increased biosynthesis of mucosal PGs, indicating that endogenous PGs may be involved in cytoprotection by acetazolamide. This is supported by the finding that acetazolamide failed to affect gastric ulcerations produced by acidified ASA when mucosal PG biosynthesis was almost completely suppressed. Pretreatment with acetazolamide did not influence the protective action of PGE2 on ethanol-induced mucosal lesions and only slightly inhibited the protective effect of PGE2 on ASA-induced gastric ulcerations. This study indicates that: (1) acetazolamide prevents ethanol- but not ASA-induced gastric mucosal lesions probably via stimulation of PG biosynthesis and (2) gastric alkaline secretion, mediated by carbonic anhydrase, is probably not an essential mechanism responsible for this cytoprotection induced by PGE2.

Role of locally generated prostaglandins in adaptive gastric cytoprotection.

This study was designed to determine the role of mucosal generation of prostaglandins (PGs) in the ability of mild irritants (20% ethanol or 5% NaCl) to protect against the formation of mucosal lesions caused by necrotizing agents (100% ethanol or 25% NaCl) or acidified aspirin (ASA). Mild irritants protected damage from necrotizing agents but not from ASA. This protection was accompanied by increased mucosal generation of PGE2 and PGI2-like substances. Exogenous PGE2 and PGI2 applied topically to the gastric mucosa in a nonantisecretory dose greatly inhibited the formation of lesions induced by either necrotizing agents or ASA. Pretreatment with indomethacin, which suppressed the generation of mucosal PGs augmented formation of lesions by necrotizing agents and partly counteracted the protective effect of mild irritants. We conclude that mild irritants, and exogenous PGs inhibit the formation of gastric lesions by necrotizing agents, at least in part, by mucosal generation of PGs.

Prevention of ethanol and aspirin-induced gastric mucosal lesions by paracetamol and salicylate in rats: role of endogenous prostaglandins.

Paracetamol or sodium salicylate given intragastrically 30 minutes before the administration of absolute ethanol or acidified aspirin dose-dependently reduced the formation of mucosal lesions. The generation of gastric mucosal prostaglandin-like activity increased with ethanol and was completely suppressed by acidified aspirin. Paracetamol or sodium salicylate given alone increased the generation of mucosal prostaglandin-like material. Indomethacin, the prostaglandin synthesis inhibitor, suppressed this effect and inhibited the protective influence of paracetamol or sodium salicylate on the production of gastric lesions.