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Biomedical subjects

E C Ellison

Publications and source records attributed to E C Ellison.

At least 73 records · Page 4Linked to original sources

Failure of secretin to stimulate gastrin release and adenylate cyclase activity in gastrinoma in vitro.

It has been hypothesized that secretin may act directly on gastrinoma through the adenylate cyclase system to cause stimulation of gastrin release. We studied gastrinoma cells in vitro to determine whether secretin would stimulate gastrin release directly and whether the gastrinoma cell membrane had a functional secretin receptor adenylate cyclase system. Fresh tumor was prepared in cell suspensions containing 1.5 X 10(6) viable cells and incubated for 2 hours with either 2 mM CaCl2 alone (control) or 2 mM CaCL2 and 0.025 U/ml secretin. The gastrin content of the cells in each incubation chamber and the medium were determined by radioimmunoassay and results were expressed as mean gastrin pg/microgram protein +/- SD. Under basal conditions the cellular gastrin content was 39.9 +/- 6.4 (control) compared with 16.7 +/- 2.1 (secretin). After 2 hours of incubation, cellular gastrin content increased in both groups: 68.5 +/- 11.9 (control) to 68.3 +/- 5.5 (secretin). However, the percent of gastrin released into the medium during incubation decreased by one half in both groups (control 37.3% +/- 4.0% to 22.2% +/- 3.0%; secretin 42.8% +/- 7.0% to 18.9% +/- 1.8%). Adenylate cyclase activity was assessed by measuring cAMP generation in fresh-frozen gastrinoma and cultured gastrinoma cell membranes. Isoproterenol (10(-5) M), PGE1 (10(-4) M), and GppNHp (guanine nucleotide) (10(-5) M) caused fivefold to 25-fold increases in cAMP generation. Secretin did not stimulate adenylate cyclase activity above basal (21.73 +/- 4.07 and 2.29 +/- 1.2 pmol cAMP/mg protein/min) for frozen and cultured gastrinoma, respectively. Secretin failed to stimulate gastrin release and adenylate cyclase in vitro. This suggests that secretin-stimulated gastrin release in vivo may not be due to a direct effect of secretin on the gastrinoma.

Adenylyl Cyclases↗

Mitochondrial dysfunction induced by pancreatitis-associated ascitic fluid.

Acute hemorrhagic pancreatitis (AHP) involves multiple organ failure probably caused by the toxic factor(s) released in pancreatitis-associated ascitic fluid (PAAF). We found that PAAF interferes with hepatic mitochondrial respiration resulting in severe disturbances in respiratory control (RCR) and ADP/O ratios. Pancreatitis was induced in dogs by retrograde pancreatic duct infusion and the resultant PAAF was centrifuged, filtered, and frozen until used. Two human PAAFs collected from AHP patients were treated in a similar manner. Rat liver mitochondrial oxygen uptake was measured at 30 degrees C before and after addition of ADP and PAAF. Paired control runs were made using pooled heat-inactivated dog serum. Tests with nine canine PAAFs showed a mean increase of 120% in state 4 respiration (P less than 0.0001). After exposure to PAAF, addition of ADP to previously coupled mitochondria did not induce state 3 respiration. The human PAAFs both showed significant increases in state 4 respiration (P less than 0.01) and a marked decrease in RCR. Dose-response tests with human and canine PAAFs showed a positive correlation between percentage increase in state 4 respiration and the concentration of PAAF used. These results confirm the presence in PAAF of mitotoxic substance(s) which cause irreversible mitochondrial damage. Inhibition of coupled mitochondrial respiration by PAAF with the resultant fall in ATP may be the causative agent for the tissue and organ damage observed in AHP.

Animals↗

High molecular weight dextran--effect on adhesion formation and peritonitis in rats.

To evaluate the effect of 32% dextran 70 instillation on intra-abdominal adhesion formation and intestinal leaks, 100 animals were prospectively, randomly, and blindly treated with a sham laparotomy (n = 10), sham plus 5 ml dextran (10), intestinal abrasion plus 2 ml (20) or 5 ml (20) of dextran or saline, or intestinal division and anastomosis plus 2 ml (20) or 5 ml (20) of dextran or saline. Autopsies were performed on the animals without knowledge of treatment group at the time of death or sacrifice at 2 weeks. Adhesions were graded 0 to 3, anastomoses were examined for leaks, and the peritoneal cavity was searched for abscesses or peritonitis. Anastomosis produced more severe adhesions than abrasion. Dextran significantly (P greater than 0.01) reduced adhesion formation but resulted in peritonitis (5/40) rather than abscess (7/40) as seen with saline.

Animals↗

Incidence and prevention of thrombosis of the subclavian vein during total parenteral nutrition.

In this study, we were able to document by radionuclide venogram the presence of thrombosis of the subclavian vein in seven of 22 patients receiving standard total parenteral infusions. By adding 3,000 U.S.P. units of heparin to each liter of infusate, we were able to reduce the number of instances of thrombosis to two in 24 patients. Although none of the patients in the heparin therapy group experienced laboratory or clinical manifestations of anticoagulation, we suggest that further studies be done to investigate the reduced heparin concentrations to determine the lowest effective level. Based upon these observations, we currently recommend that 3,000 U.S.P. units of heparin be added to each liter of total parenteral nutrition solution infused through a subclavian venous catheter.

Female↗

Pancreatic polypeptide in acute pancreatitis and small-bowel infarction in dogs.

Serum and urine concentrations of pancreatic polypeptide (PP) were measured during experimental acute hemorrhagic pancreatitis and small-bowel infarction in dogs. The mean serum PP concentration in animals with pancreatitis increased markedly after 1 hr and remained elevated, while the mean serum PP concentration in the animals with infarction showed a late trend to increase. The urine PP concentration in pancreatitis increased nonsignificantly, whereas, during bowel infarction, there was no increase. In the infarction group, PP clearance correlated with the serum PP concentration. During pancreatitis, PP was cleared independently of the serum PP concentration. The results suggest that during acute hemorrhagic pancreatitis there is an acute release of PP related to immediate cell injury in the pancreas. The high serum concentration of PP may lead to an override of the normal renal handling of PP. In small-bowel infarction there may be a delayed mode of PP release.

Acute Disease↗

Preoperative percutaneous transhepatic biliary decompression lowers operative morbidity in patients with obstructive jaundice.

Percutaneous transhepatic biliary decompression is a safe and potentially helpful procedure. If done correctly, it will accomplish adequate decompression of the biliary tree and permit hepatic function to return to a more normal state preoperatively. The time gained while waiting for the bilirubin level to decrease can be used for adequate preoperative preparation of the patient. Use of this technique may make it possible for operative treatment of obstructive jaundice to return to a two-stage procedure, the first stage being percutaneous transhepatic biliary decompression.

Adult↗

Prevention of early failure of stapled gastric partitions in treatment of morbid obesity.

Clinical observations and data obtained in animal experiments indicate that the gastric partition is most susceptible to the stresses of solid food boluses between the second and sixth postoperative weeks, predisposing the operation to early failure. Tensiometer studies indicate that by the sixth to the eighth postoperative week, the staple line is as strong as uninjured stomach. Liquid diet restriction for eight weeks after gastric partitioning reduces the incidence of early operative failure. Until safe and effective methods of increasing staple line strength are established, all patients having gastric partitioning should be restricted to a liquid diet for eight weeks after operation.

Animals↗

Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal.

A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypergastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had unresectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long-term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperatively to control the gastric hypersecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives.

Adenoma, Islet Cell↗

Carcinoembryonic antigen in cerebrospinal fluid of adult brain-tumor patients.

Carcinoembryonic antigen (CEA) was measured in plasma and cerebrospinal fluid (CSF) in patients with neoplasms and non-neoplastic neurologic conditions of the central nervous system (CNS). Seventy-two control patients had a mean CEAcsf of 0.04 ng/cu cm, 31 patients with benign tumors had a mean CEAcsf of 0.03 ng/cu cm, and 21 patients with malignant CNS tumors had mean CEAcsf of 21.7 ng/cu cm. In the absence of intradural metastasis, the existence of non-CNS malignancies did not cause CEA to appear in the CSF. There was no relationship between the plasma and CSF levels of CEA. The CSF is normally free of CEA, and its detection is strongly suggestive of either primary or secondary intradural malignancy. The titres of CEA decline with effective therapy, and may be of use in monitoring treated patients for recurrence.

Adolescent↗

Correction of hypersplenism following distal splenorenal shunt.

The effect of splenorenal shunt on hypersplenism was assessed in 47 patients with splenomegaly, 26 of whom had significant thrombocytopenia or leukopenia. Of 16 patients with thrombocytopenia, platelet count returned to normal in 15 (94%) following operation, an improvement which was statistically highly significant (P less than 0.001). Of 16 patients with leukopenia, leukocyte count returned to normal in 11 (69%), also a highly significant improvement (P less than 0.001). Dramatic relief of hypersplenism occurs in the majority of patients following splenorenal shunt. Thrombocytopenia is more consistently corrected than is leukopenia. The etiology of liver disease appeared not to be a factor, but leukopenia was corrected more consistently in alcoholic than in nonalcoholic patients, while there was no difference in the postoperative response of thrombocytopenia to the operation. Long-term follow-up in 26 patients demonstrated sustained improvement in 57% of patients with preoperative leukopenia and 78% of patients with thrombocytopenia. Since significant improvement in leukopenia and thrombocytopenia will occur following the distal splenorenal shunt, hypersplenism is not a contraindication to this procedure.

Female↗

Micro-determinations of alpha-tocopherol in tissue lipids.

It has been shown that the determination of small amounts of tocopheral in tissue lipids by methods that use, in sequence, saponification, extraction, TLC and colorimetric assay, is greatly influenced by the concentration of soap in the saponification mixture. Soaps appear to interfere with the recovery of tocopherols during the subsequent extraction step. Based on this knowledge a method is described that was used to measure as little as 15 to 20 ng of tocopherol in 3 to 4 mg of lipid obtained from rat retinas. Presumably the method would be applicable to other tissues as well. The results show that the rat retina is readily depleted of tocopherol if none is included in the diet.

Animals↗