Clinical significance of plasma neurotensin determination on chololithiasis

254 SOMATOSTATIN ANALOG IMPROVES SYMPTOMS OF DUMPING SYNDROME WITH PREVENTION OF ORTHOSTASIS AND HYPERINSULINEMIA: LACK OF EFFECT ON HEMOCONCENTRATION AND GASTRIC EMPTYING. Soudah H, Hasler W, Owyang C. Dept. of Int. Med., Univ. of Michigan, Ann Arbor, MI, USA. The somatostatin analog octreofide is beneficial in dumping syndrome but its mechanism of action is unknown. We studied 5 dumping syndrome patients (2 Billroth II, 3 Roux-en-Y) to test how octreotide improves symptoms. Studies were performed 45 min after double-blind octreotide (50 lag sc) or placebo injection. We verified the efficacy of octreotide by assessing symptoms from 0 (none) to 4 (severe) after 75gm oral glucose. Symptoms after octreotide were much less than place-bo for diarrhea(0.0!-0.0 vs 3.5_+0.3), faintness(1.0!-_0.4 vs 3.8_+0.2), and palpitations(0.8_+0.2 vs 3.2 _+0.5), p<0.02. We tested hemodynamic responses to oral glucose. Orthostatic pulse increases were 36+l/min for placebo vs 16+3/min for octreotide. Hemoconcentration after oral glucose was tested with hematocrit(Hct) and plasma osmolarity(Osm). Increases in Hct (1.6+0.2 vs 1.5+0.6%) and Osm (105:2 vs 9i-_lmosm) were identical with placebo or octreotide, suggesting that orthostasis is not due to fluid shifts alone but may involve release of unknown vasoactive factors which are blocked by octreotide. Hypoglycemia may cause late dumping symptoms. With placebo, plasma glucose decreased to 56+8mg/dl, 1-3 hrs after oral glucose. Octreotide prevented late hypogly-cemia (167+38mg/dl) and blunted postingestion insulin increases from 80-2_23to 32+13 uU/ml. Finally dumping is associated with rapid liquid gastric emptying. We performed liquid and solid gastric scintiscans to test if octreotide delays gastric emptying. The tl/2 of emptying of liquids was the same for placebo (10"Z_5min)and octreotide (12+_5 min). The % of a solid meal emptied at 2 hrs was also the same (placebo 42+ 17%, octreotide 27+13%). Thus octreotide does not delay gastric emptying in dumping. Conclosion: Octreotide amelioration of symptoms in dumping syndrome is associated with reduction of orthostasis and hypoglycemia. This beneficial effect is likely due to inhibition of release of vasoactive substances and insulin by octreotide. In contrast, octreotide does not prevent hemoconcentration after a glucose challenge or delay rapid gastric emptying.

EFFECT OF FISH AND FISH OIL ON GASTRIN, SOMATOSTATINAND PROSTAGLANDINS IN CYSTEAMINE INDUCED DUODENAL ULCER. Soveny C and Hansky J, Departmentof Medicine, Monash MedicalCentre, Clayton,Australia. Studies have suggestedthat omega 3 and 6 fatty acids reduce the incidenceof experimentallyinduced duodenal ulcers. The mechanism is unknown but reduction of acid secretion and changes in prostaglandinsmay be factors. In addition changes in gastrin or somatostatinhave not been explored in some modelso! experimentalulcer. To further explainthis action of fatty acids,female rats were fed pelletssoaked in Maxepa,olive oil or a diet of smoked cod for 3 weeks, injectedsubcutaneouslywith Cysteamineand then sacrificedat 48 hours. The stomach and duodenum were inspectedfor ulceration and antral and duodenal mucosawas extractedfor measurementof gastrin (GAS), somatostatin (SOM) and prostaglandin E2 (PGE2) by RIA. Ulcer incidence and concentrationsof PGE2, GAS and SOM are shown in the table. Duodenal PGE2 was significantlylower in both Maxepaand cod fed rats compared with olive oil whilst antral PGE~was significantlylowered in Maxepafed rats. The only significantchange in antral or duodenal GAS and SOM was a slgniticantlylower antral GAS in the cod fed rats. Duodenal Ulcer N=18 Olive Maxepa Cod

13 6 2

PGE2 pg/mg protein 453+104 153+21 206+49

DUODENAL Gastrin Somatostatin pm/mg pm/mg protein protein 3.4+_1.4 7.6+1.4 3.6+1.2 3.7+0.7 3.4+_0.8 8.4+_2.2

PGE2 pg/mg protein 481+_67 248+_43 431+132

ANTRAL Gastrin Somatostatin pm/mg pm/mg protein protein 66.1+_9.2 32.1+_6.3 63.3+8.2 17.5+_.3.1 31.6+_2,8 20.5_.+2.9

Conclusion: Fish and fish oils protect rats from Cysteamineinduced duodenal ulcers. This was accompanied by a loweredduodenal PGE2 and a lowered antral GAS in cod fed rats whilst only the PGE2 was lower in the Maxepagroup. The mechanismwherebyfish and fish oils protect duodenal mucosa may be via a loweredgastrin releaseand decreased PGE2. Whether this reflects a rapid turnover is not known.