Theodore A. Stein

Risk factors associated with rapid growth of small abdominal aortic aneurysms

BACKGROUNDnApproximately 50% of patients who have a ruptured abdominal aortic aneurysm will die. To identify those patients who may be at high risk for rupture, we determined the risk factors for the rapid expansion of the aorta.nnnMETHODSnThe growth of 514 aneurysmal aortas was followed in this study. The size of each was measured by ultrasonography at 6- to 12-month intervals until a critical size was reached or a rapid expansion of the aorta occurred. Possible risk factors for rapid expansion were determined from both initial evaluation and clinical laboratory results.nnnRESULTSnThe initial size varied from 2.5 cm to 6.0 cm. The expansion rate of the aorta was 0.5 cm/yr or less in 401 patients (78%), between 0.5 and 1.0 cm/year in 50 patients (10%), and 1.0 cm/year or more (rapid expansion) in 63 patients (12%). Elective repair of aneurysms was done before rupture. Multivariate analysis indicated that the risk factors associated (p < 0.03) with rapid expansion were advanced age, severe cardiac disease, previous stroke, and history of cigarette smoking. The incidence for rapid expansion increased (p < 0.01) in older patients with aneurysms larger than 3 cm and in younger patients with aneurysms larger than 4 cm.nnnCONCLUSIONSnRisk factors associated with rapid expansion of the aorta have been determined and may help identify the patient at high risk for rupture. Ultrasonographic surveillance should be performed more frequently in these patients to help prevent rupture.

Hepatic fat accumulation during liver regeneration

Fat accumulates in the regenerating liver after partial hepatectomy. The role of intracellular acyltransferases in the synthesis of triglycerides was studied in the liver. Two-thirds hepatectomy was performed in 14 rats. An additional 14 rats had laparotomy only (sham group). Animals were sacrificed at 18 or 24 hr after operation. After 18 hr, microsomal sn-glycerol 3-phosphate acyltransferase specific activity was increased from 708 to 956 pmole of glycerol 3-phosphate incorporated X min-1 X mg-1 protein and the triglyceride content was increased from 2.2 to 12.6 mg/g liver. At 24 hr the microsomal enzyme activity was again increased from 742 to 1203 pmole of glycerol 3-phosphate incorporated X min-1 X mg-1 protein and the triglyceride content rose from 1.9 to 13.9 mg/g liver. A correlation existed between the microsomal enzyme activity and the triglyceride level (r = 0.608, P less than 0.05). The mitochondrial enzyme activity was not increased. At 24 hr peroxisomal dihydroxyacetone acyltransferase activity was elevated from 375 to 523 pmole of dihydroxyacetone phosphate incorporated X min-1 X mg-1 protein but showed no correlation with the triglyceride content; the microsomal activity of the enzyme was not increased. Cytoplasmic NAD+-dependent alpha-glycerol 3-phosphate dehydrogenase decreased by 24 and 32% at 18 and 24 hr. These data indicate that the microsomal sn-glycerol 3-phosphate acyltransferase activity has a major role in promoting triglyceride synthesis during liver regeneration.

Effect of verapamil on the gastric mucosal level of PGE2 during stress

Prostaglandin E2 is one of the factors in the maintenance of gastric mucosal integrity and verapamil, a calcium channel blocker, has been shown to reduce gastric mucosal ulcerations during stress. To investigate whether this protective effect of verapamil is mediated via PGE2, four groups of 20 Holtzman rats were given either 1 ml of normal saline (NS) intraperitoneally (ip): 1 mg/kg of indomethacin (I) ip; 2 mg/kg of verapamil (V) ip or I followed by V. Then 10 animals from each group were submitted to stress by the cold-restraint method. After sacrifice, gastric mucosal ulcerations were counted and specimens of nonulcerated mucosa were assayed for PGE2 by HPLC. Stress-induced mucosal ulcerations were associated with a significant decrease in the gastric mucosal levels of PGE2 (from 64.2 to 32.7 pg; P less than 0.05). This effect was magnified by the administration of indomethacin (down to 21.0 pg). Verapamil significantly increased PGE2 levels both in the stressed (48.0 pg) and unstressed (99.9 pg) animals and significantly reduced ulcerogenesis when compared to either NS- or I-treated groups. This effect of verapamil was completely blocked by the administration of indomethacin. In conclusion, verapamil stimulates PGE2 synthesis and its protective effect against stress-induced mucosal damage seems to be mediated by PGE2.

Picogram measurement of prostaglandin E2 synthesis by gastric mucosa by high-performance liquid chromatography

Prostaglandin biosynthesis by gastric mucosa was determined by a 1-min incubation, solvent extraction, and reaction with panacyl bromide. The prostaglandin ester was measured by normal-phase high-performance liquid chromatography. The prostaglandin E2 levels of normal gastric mucosa of rats and swine were 90.6 +/- 31.0 and 79.8 +/- 39.8 pg/min/mg tissue, respectively. This method was sensitive to 40 pg and specific for prostaglandin E2.

Arachidonic acid protection of rat mucosa against stress ulceration

To evaluate the effect of arachidonic acid (AA), a prostaglandin precursor, on the mucosal level of PGE2 and its possible protective role against stress ulcerations, 40 Holtzman rats were divided into four groups: Group I intragastrically receiving 1 ml of normal saline (NS); Group II, NS pretreatment followed by stress; Group III, intragastric AA pretreatment without stress; and Group IV, intragastric AA followed by stress. AA was administered as a 120 mM solution in a nonionic detergent, adjusted to a pH of 8.0. Stress was provided by the cold-restraint method. After sacrifice, the number of gastric mucosal ulcerations were counted. Specimens of nonulcerated mucosa were assayed for PGE2 by derivatization with panacyl bromide and by using high-performance liquid chromatography. The animals in Groups I, III, and IV developed no gastric ulcerations and their mucosal prostaglandin E2 remained at a normal level, while those in Group II had a significant reduction of mucosal PGE2 (P less than 0.05) and a significantly increased number of gastric ulcerations (P less than 0.002). These data indicate that stress-induced mucosal ulcerations are associated with significant decreases in the gastric mucosal levels of PGE2. Intragastric administration of arachidonic acid prevents the formation of stress mucosal ulcerations and maintains a normal level of mucosal PGE2.

Diagnostic value of liver function tests in bile duct obstruction.

Serological tests may be of value in differentiating acute and chronic bile duct obstruction because the rate of alteration of hepatic cellular integrity and function will affect the rate of cellular product release. In a canine model the common bile duct was obstructed either suddenly (N = 7) or gradually (N = 5). A control group (N = 5) had the common bile duct dissected free from the surrounding tissues. Blood was taken before and 1, 2, 4, 7, 11, 14, 17, 21, and 28 days after initiating obstruction. Serum alkaline phosphatase, bilirubin, aspartate aminotransferase, alanine aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase levels were significantly greater with sudden compared to gradual occlusion, and the values were larger than those in the control. The range of values of alkaline phosphatase, bilirubin, and aspartate aminotransferase did not overlap in the acute and chronic groups at specific times. Serum albumin and total protein were normal in all groups. The magnitude of alkaline phosphatase, aspartate aminotransferase, and bilirubin elevation may help in the differentiation of acute and chronic biliary obstruction.

High-performance liquid-chromatographic assay for prostaglandins with the use of p-(9-anthroyloxy)phenacyl bromide

Gastric mucosa of rats and swine was incubated in buffer for 1 min to produce prostaglandins (PGs). After extraction and derivatization with p-(9-anthroyloxy)phenacyl bromide, the prostaglandin esters were determined by high-performance liquid chromatography. A 20-microliter sample was injected into a microparticulate silica gel column with a mobile phase of dichloromethane-acetonitrile-methanol (90:9:1). At a flow-rate of 1.5 ml/min the retention times of the prostaglandin esters were 7.14 min (internal standard), 7.90 min (PGF2), 10.05 min (thromboxane2), 12.26 min (6 alpha-keto-PGF1 alpha) and 13.98 min (PGF2 alpha). In spite of high sensitivity (0.1 ng per sample) for PGE2 and PGF2 alpha, only PGE2 synthesis was observed.

Determination of elastase activity by reversed-phase high-performance liquid chromatography

The action of elastase on elastin was measured by high-performance liquid chromatography with on-line post-column derivatization. After alkaline hydrolysis, a 20-ml sample was injected into a ODS-2 gel column. An elastin-specific dipeptide, Val-Pro, and the internal standard, Gly-Leu, were eluted by a linear gradient of 0 to 10% of 1-propanol in 50 mM heptafluorobutyrate (pH 3) at a flow-rate of 1 ml/min. The eluent was reacted with fluorescamine, and the fluorescent products were measured. Retention times for Val-Pro and Gly-Leu were 17.33 and 23.54 min. The peak areas of 0.2-16 micrograms of Val-Pro gave a straight-line plot. Elastase activity was constant from 6 to 24 h and was 0.95 +/- 0.02 (S.D.) micrograms/h. The method may be useful for the measurement of the elastolytic activity in some diseased tissues.

The effects of ileal resection with cholecystectomy on bile salt metabolism in the prairie dog.

The adverse effects of ileal resection on bile salt metabolism may be aggravated by cholecystectomy. Female prairie dogs had either sham laparotomy, cholecystectomy, distal 50% small bowel resection, or cholecystectomy and distal 50% small bowel resection. After 4 weeks the common bile duct was cannulated and bile collected for up to 12 hr. Bile salt pool size and synthetic rate were measured from the washout curve. Bile salt, phospholipid, and cholesterol concentrations were determined. Bile salt pool size was reduced after cholecystectomy and after ileal resection. Cholecystectomy plus ileal resection further lowered the pool size, increased the synthetic rate, and increased the proportion of secondary bile salts. Cholecystectomy increased the synthesis and the concentration of bile salts in hepatic bile and altered the proportions of biliary lipids. Ileal resection decreased the concentration of hepatic bile salts with the formation of noncholesterol stones. The drastic reduction in pool size with the combined operation might be expected to lead to fat malabsorption. The higher concentration of bile salts after the combined operation compared with ileal resection alone reflects a possible beneficial effect of cholecystectomy.