Gordon L. Kauffman

Comparison of the costs associated with medical and surgical treatment of obesity

BACKGROUND We compared the long-term costs and outcomes of gastric bypass versus medical therapy (very low-calorie diet plus weekly behavioral modification) for obese patients. METHODS A successful outcome was defined as the loss of at least one third of excess weight that was maintained for the duration of the study. A minimal cost was assigned:

Aspirin-Induced Gastric Mucosal Injury: Lessons Learned From Animal Models+

3000 for medical and

Awake epidural anesthesia is associated with improved natural killer cell cytotoxicity and a reduced stress response

24,000 for surgical treatment. A cost per pound of weight lost for all patients successfully monitored was calculated. The Federal Trade Commission recently asked all weight loss programs to report this cost for patients at least 2 years after therapy. RESULTS A total of 201 patients entered surgical and 161 entered medical therapy. The surgical group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6 versus 41.2 +/- 0.7, p < 0.01), but each groups lowest mean body mass index was similar (31.8 versus 32.1, respectively). A significantly higher percentage of patients in the surgical versus the medical group were still successful at year 5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost of surgical therapy in the sixth posttreatment year (both more than

Differential regulation of gastrin and somatostatin secretion from isolated perfused rat stomachs

250/pound). CONCLUSIONS Surgical treatment appears to be more cost-effective at producing and maintaining weight loss. It is imperative that long-term follow-up studies be funded to definitely establish this finding.

Lack of Correlation Between Mucus Gel Thickness and Gastric Cytoprotection in Rats

This review of the mechanisms by which aspirin causes gastric mucosal damage points to the involvement of two potential mechanisms. Aspirin, which inhibits cyclooxygenase, is rapidly deacetylated to salicylate. Salicylate is toxic to cells and affects mucosal barrier function, reduces cytosolic adenosine triphosphate, stimulates sodium transport, and increases proton dissipation from surface epithelial cells. Cyclooxygenase inhibition makes the gastric mucosa more susceptible to injury, inhibits mucus and bicarbonate secretion, alters the physicochemical nature of mucus, stimulates fundic but not antral [3H]thymidine incorporation, and reduces epithelial surface hydrophobicity. No single mechanism seems to be involved. It is likely, instead, that the toxic effects of salicylate and the effect of cyclooxygenase inhibition work in concert to render the mucosa more susceptible to injury, resulting in mucosal damage.

Salicylic Acid Blocks Indomethacin- and Aspirin-Induced Cyclo-Oxygenase Inhibition in Rat Gastric Mucosa

BACKGROUND Laparotomy under general anesthesia is associated with depressed natural killer cell cytotoxicity (NKCC) and compromised clearance of tumor cells. We tested the hypothesis that awake epidural anesthesia (AEA) improves NKCC compared to conventional general endotracheal anesthesia (GEA). PATIENTS AND METHODS Preoperative, perioperative, and postoperative (day 3) NKCC, plasma epinephrine, norepinephrine, cortisol levels, and 24-hour urinary cortisol levels were measured in 20 patients undergoing open colectomy under either AEA or GEA. RESULTS Preoperative and postoperative measurements were not significantly different in the two groups. Patients receiving GEA had a significant reduction in NKCC from 36% +/- 4% preoperatively to 22% +/- 4% perioperatively (P = 0.02). Patients receiving AEA had no significant change in NKCC. Perioperative plasma epinephrine and cortisol levels were higher with GEA than AEA. The perioperative 24-hour urinary cortisol excretion values were significantly higher in the group receiving GEA, suggesting a greater stress hormone response in this group compared to AEA patients. CONCLUSIONS Compared to GEA, AEA appears to preserve perioperative NKCC. This effect may be related to an attenuated stress hormone response associated with AEA. Cancer patients may have improved killing of embolized tumor cells during surgery performed under AEA.

Central nervous system action of calcitonin to alter experimental gastric ulcers in rats

In order to examine the relationships between gut somatostatinlike immunoreactivity and gastrin, we studied the regulation of their secretion from isolated perfused extrinsically denervated rat gut preparations by bombesin nonapeptide and carbamyl choline. Carbamyl choline inhibited somatostatinlike immunoreactivity and stimulated gastrin secretion in a dose-dependent fashion with maximum responses at 10−6 M. These effects of carbamyl choline were abolished by atropine but not by hexamethonium. Conversely, bombesin nonapeptide stimulated both somatostatinlike immunoreactivity and gastrin secretion in doses as low as 10−10 M for somatostatinlike immunoreactivity and 10−9 M for gastrin. Neither atropine nor hexamethonium influenced bombesin-stimulated gastrin release but both agents abolished bombesin-stimulated somatostatinlike immunoreactivity secretion. The combination of carbamyl choline and bombesin affected somatostatinlike immunoreactivity and gastrin secretion in an identical fashion as carbamyl choline alone. These results suggest that somatostatinlike immunoreactivity and gastrin secretion from the gut are differentially regulated. Carbamyl choline stimulates gastrin release and inhibits somatostatin release by activation of muscarinic cholinergic receptors. Bombesin stimulates somatostatin release by activation of neural pathways involving both nicotinic and muscarinic cholinergic receptors. However, stimulation of gastrin release by bombesin does not involve cholinergic neural pathways and may reflect a direct action on gastrin cells.

Measurement of prostaglandin E2 in interstitial fluid from the dog stomach after feeding and indomethacin.

The effect of various cytoprotective agents on the thickness of gastric mucus gel layer in rats was studied. It was hypothesized that an increase in the mucus gel layer might be involved in cytoprotection. The results show that this is not the case. Neither prostaglandin E2, 16,16-dimethyl prostaglandin E2, nor mild irritants (20% ethanol, 0.35 M HCl, 20% glucose, 20% mannitol), all given orally, altered the thickness of the mucus gel layer, although these agents were found to be cytoprotective, i.e., inhibiting the formation of gastric mucosal necrotic lesions caused by oral administration of absolute ethanol. The only agents that significantly increased the thickness of the mucus gel layer were a hypertonic solution (4% NaCl) and sodium salicylate. We conclude that if mucus plays a role in cytoprotection, it is not by virtue of an increase in thickness of the gel layer adherent to the gastric mucosa.

Role of central prostaglandin E2 in the regulation of gastric acid secretion in the rat

Salicylic acid reduces gastric mucosal lesions induced by aspirin and indomethacin. Aspirin and indomethacin reduce gastric mucosal cyclo-oxygenase activity. These studies were designed to determine whether or not salicylic acid interacts with gastric mucosal cyclo-oxygenase, decreasing the inhibitory effect of aspirin and indomethacin as has been observed in platelets and vascular tissue. The interaction between salicylic acid and two cyclo-oxygenase inhibitors, indomethacin and aspirin, was assessed on ex vivo prostaglandin generation in the rat gastric mucosa. Salicylic acid (100 mg/kg) was administered orally 30 min before the subcutaneous injection of either indomethacin (0.5-10 mg/kg) or aspirin (5.0-20 mg/kg). Pretreatment produced a shift of the mean 50% inhibitory dose for PGF2 alpha formation from 0.92 to 7.6 mg/kg for indomethacin and from 7.8 to 20 mg/kg for aspirin. Similar results were achieved with ex vivo prostacyclin synthesis as measured by the level of 6-keto-PGF 1 alpha. These data are consistent with competitive enzyme kinetics, and may, in part, explain the protective effect of salicylic acid against the ulcerogenicity of aspirin and indomethacin on the gastric mucosa.

Gastric bicarbonate appearance with ethanol ingestion. Mechanism and significance.

The central nervous system action of calcitonin to influence various experimental models of gastric ulcers and gastric function was studied in rats fasted for 24 h. Intracisternal injection of salmon calcitonin (5 micrograms) completely suppressed gastric ulcerations induced by exposure to cold restraint stress, intracisternal injection of a stable thyrotropin-releasing hormone analogue, or peroral administration of aspirin. By contrast, intracisternal calcitonin enhanced gastric lesions elicited by peroral administration of 40% ethanol or 0.6 N HCl. Calcitonin action was dose-dependent (0.01-1 microgram) and central nervous system mediated inasmuch as intravenous calcitonin, given at a dose 50-fold higher than that effective intracisternally, did not significantly modify gastric mucosal injuries elicited by aspirin or ethanol. Intracisternal injection of calcitonin at 0.01 microgram inhibited gastric acid output by 90% in pylorus-ligated rats and suppressed gastric emptying of a liquid meal by 63%-94% in doses ranging from 0.01 to 5 micrograms. Prostaglandin generation in the gastric mucosa was not modified by intracisternal injection of calcitonin. These results demonstrate that intracisternal calcitonin acts within the brain to potently prevent ulcer formation elicited by stress, thyrotropin-releasing hormone analogue, or aspirin, but is not cytoprotective against necrotizing agents. Calcitonin action is not related to modification of gastric prostaglandin generation but it may involve the inhibition of gastric secretory and motor function.