Biomedical subjects

E C Ellison

Publications and source records attributed to E C Ellison.

At least 19 recordsLinked to original sources

PubMed1991

Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients.

Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. However its safety, efficacy, and morbidity have yet to be fully evaluated. During the first 6 months of 1990, we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8% (8 of 100 patients; 4 major, 4 minor). There were 81 women and 19 men, with a mean age of 46.1 years (range, 17 to 84 years). All patients had a preoperative history consistent with symptomatic biliary tract disease, and most had proved gallstones by sonography. This included four patients with acute cholecystitis. Mean operating time improved significantly from month 1 to month 6 (122 +/- 45.4 minutes versus 78.5 +/- 30 minutes, respectively), indicating a rapid learning curve. Mean hospital stay was 27.6 hours, reflecting a policy of overnight stay. Postoperative narcotic requirements were limited to oral or no medications in more than 70% of patients. A regular diet was tolerated by 83% of the patients by the morning following the procedure. Median time of return to full activity was 12.8 +/- 6.8 days after operation. In addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy (n = 58) (mean, $3620.25 +/- $1005.00 versus $4251.76 +/- $988.00). There was one minor bile duct injury requiring laparotomy and t-tube insertion, two postoperative bile collections, and one clinical diagnosis of a retained stone that passed spontaneously. Four patients required conversion to open cholecystectomy because of technical difficulties with the dissection. Although there is a significant learning curve, laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. Laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy, and, as with all operations, it should be performed with meticulous attention to technique.

Adolescent↗

PubMed1991

Complications of laparoscopic cholecystectomy.

As laparoscopic cholecystectomy has become more widely practiced, the full spectrum of complications associated with this technique is being realized. We have performed 283 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 5.3% (15 of 283 patients; six major complications, nine minor complications). Major complications included one bile duct injury requiring laparotomy and t-tube insertion and two patients with retained stones. Symptomatic bile leakage occurred in three patients (1%). Two of these bile leaks were from accessory ducts entering the gallbladder bed; the third leak was secondary to a cystic duct leak. Eight patients (2.8%) required conversion to open cholecystectomy. Minor complications included three patients with subumbilical wound infections, two patients with urinary tract infections, one patient with costochondritis after operation, and three patients with prolonged hospital stays (more than 48 hrs) caused by ileus or fever. Several patients with life-threatening complications, including two patients who ultimately died, were transferred to our care from other centers. These included two patients with common duct injuries combined with duodenal perforations (one of whom died), one patient with a complete common duct transection, one patient with major common hepatic duct injury, and two patients with further instances of bile leakage. Laparoscopic cholecystectomy can be performed safely, and it can be associated with life-threatening complications. Prevention of complications is dependent on proper patient selection, meticulous technique, and an accepting attitude toward conversion to "open" cholecystectomy.

Adult↗

PubMed1990

Gastrinoma in vitro: morphological and physiological studies of primary cell cultures.

Functional gastrin-containing tumor cells were maintained for up to 8 wk without fibroblastoid cell overgrowth. Short-term cultures consisted mainly of colonies composed of small polygonal cells, 70%-90% of which stained positive for immunoreactive gastrin. Cultures exhibited limited growth but viability remained high for 2-3 wk. Culture medium contained component I, and gastrin 34, 17, and 14. With time the major C-terminal gastrin species in medium changed from gastrin 17 at 3 days to gastrin 34 at 5 wk. Extracts of cultured cells contained gastrin 34, 17, and 14; gastrin 17 was the major form detected at all times. Ultrastructurally, cultured tumor cells retained morphological integrity for several weeks; however, with time changes in the appearance of the secretory granules accompanied by evidence of cellular retrodifferentiation were gradually observed. Secretin, gastrin-releasing peptide, 8-bromoadenosine 3':5'-cyclic monophosphate, and phorbol, 12-myristate, 13-acetate stimulated the release of gastrin from cultured cells in a time-dependent fashion. Secretin, bombesin, gastrin-releasing peptide, L-tryptophan, and ethylamine stimulated gastrin release in a dose-dependent fashion. Somatostatin 14 inhibited secretin, bombesin, and gastrin-releasing peptide stimulated gastrin release but did not alter basal release. Cultured cells demonstrated de novo gastrin synthesis, evidenced by their ability to incorporate radiolabeled amino acids into immunoadsorbable gastrinlike material. Primary cultures of gastrin-containing tumor cells free from stromal contamination offer unique advantages for studies of factors that regulate the synthesis and secretion of gastrin and may prove of potential value for studies on cell differentiation and growth.

Culture Media↗

PubMed1990

The use of endoscopy to treat bronchobiliary fistula caused by choledocholithiasis.

Bronchobiliary fistula is a rare disorder consisting of the formation of a passageway between the biliary ducts and the bronchial tree. We describe an 87-yr-old woman who had a bronchobiliary fistula secondary to obstruction caused by multiple common bile duct stones. The diagnosis was confirmed by the presence of bile in the sputum and transhepatic cholangiography. Successful stone extraction with balloon and basket techniques and endoscopic sphincterotomy decompressed the biliary tract and was followed by healing of the bronchobiliary fistula without surgical intervention, which has heretofore been considered the only successful means of treatment.

Aged↗

PubMed1989

The importance of objective data in the diagnosis of pancreatitis.

In 78 patients with likely pancreatitis, we used laparotomy, computerized tomography, ultrasonography and other information to make an objective diagnosis of pancreatitis. Laboratory studies included serum amylase, amylase isoenzymes and lipase. We found that both amylase and lipase are highly sensitive tests and P3 amylase by electrophoresis on agarose to be specific; a combination of these tests is recommended to assist in the diagnosis of pancreatitis. The frequent occurrence of an abnormal amylase and lipase in patients without pancreatitis is suggested as the cause of overdiagnosis of this disorder. A markedly increased amylase or lipase was always associated with pancreatic disease.

Adolescent↗

PubMed1989

Effects of enteric neural stimulation on chloride transport in human left colon in vitro.

Nonpathological segments of muscle-stripped left colon from patients undergoing surgery for carcinoma, diverticulitis, or other causes were set up in flux chambers in order to determine the influence of intrinsic neurons on ion transport. In the basal state, both sodium and chloride were actively absorbed, and there was no significant residual ion flux. Electrical field stimulation of the intrinsic mucosal innervation evoked an increase in short-circuit current that was dependent on stimulus frequency and strength. The response was mimicked by scorpion venom, which is known to depolarize neurons, and was nearly abolished by tetrodotoxin, which prevents neurotransmitter release. Atropine reduced, but did not abolish, the response to neural stimulation. Carbachol, aminophylline, and theophylline significantly increased short-circuit current above basal levels. Electrical field stimulation evoked an increase in short-circuit current that could be accounted for by a decrease in net chloride absorption without any significant effect on sodium absorption or residual ion flux. These results suggest that ion transport in the human left colon is regulated by intrinsic submucosal cholinergic neurons as well as other neuronal types, and activation of these nerves could provide the basis for certain diarrheal disorders.

Aged↗

PubMed1989

Hepatic recovery after biliary decompression of experimental obstructive jaundice.

Obstructive jaundice was produced in 11 dogs by common bile duct ligation for 4 weeks, then biliary decompression was performed by bilioenteric anastomosis. Animals were regularly studied over the 2 months after decompression by the following methods: (1) serum biochemistry was monitored; (2) light microscopic changes in serial liver biopsies were graded; (3) the respiratory characteristics of isolated hepatic mitochondria, obtained by open liver biopsy, were studied using an oxygen micro-electrode system; (4) in vivo handling of an hepatobiliary imaging agent (diisopropyl iminodiacetic acid) was studied by dynamic liver scintiscanning. None of these liver assessments were normalized after 7 to 10 days of biliary decompression. Our study suggests that biliary decompression of patients with extrahepatic biliary obstruction requires long periods of time to enable major recovery of the abnormal liver function induced by biliary obstruction.

Anastomosis, Surgical↗

PubMed1989

Lymphocyte function in obstructive jaundice.

Sepsis is a major factor in the high mortality and morbidity after surgery for obstructive jaundice. Several studies have suggested that reticuloendothelial function is depressed, but changes in lymphocyte function are poorly understood. A model of obstructive jaundice has been produced by chronic common bile duct ligation in eight dogs. In vitro lymphocyte studies were performed both at 2 and 3 weeks duration of jaundice and compared with simultaneous healthy control subjects. Icteric animals showed no abnormality of natural killer cell function. Relative numbers of T and B lymphocytes and their subsets were unchanged. T lymphocyte responses to three mitogens were not significantly reduced in jaundiced animals. Serum immunoglobulin levels were unchanged compared to those before surgery apart from a significant rise in immunoglobulin A. No evidence of circulating immunosuppressive factors was found by mitogen testing on normal lymphocytes in the presence of pooled serum from jaundiced animals, normal serum, or normal serum with added bilirubin. Our study does not suggest that impairment of lymphocyte function contributes significantly to the dangers of sepsis in obstructive jaundice.

Animals↗

PubMed1989

DISIDA kinetics measure liver function in dogs.

We have investigated the ability of 99Tcm-disofenin (DISIDA) kinetics to measure liver function. Two approaches have been used: first, quantitative analysis of serial liver images, and second, clearance estimation from whole blood concentration-time data. Graded liver dysfunction was produced in 11 dogs over three months by common bile duct ligation and surgical relief of biliary obstruction one month later. The kinetic analysis of serial liver images showed clear abnormalities during biliary obstruction, with calculated rates of liver uptake falling in stages from 11.09 to 5.15 cts s-1 (p less than 0.001), and rates of elimination from the liver from 8.8 to 1.6 x 10(-4) cts s-1 (p less than 0.0001). These parameters paralleled the deterioration and recovery of liver function through the experimental period, and had not fully recovered 7 weeks after relief of biliary obstruction (10.5 and 6.2 x 10(-4) cts s-1 respectively). Serial blood sampling after injection of DISIDA permitted calculation of whole blood disposition rates (for hepatic clearance). Mean values fell from 256 to 67 ml min-1 with chronic biliary obstruction (p less than 0.001), and returned to almost normal (206 ml min-1) 10 days after surgical relief of biliary obstruction. It is clear that the gradual nature of recovering liver function was more sensitively identified by image analysis than serial blood data. Serial liver biopsies showed marked changes following biliary obstruction. These improved over a period of 7 weeks following its relief, when there was still considerable residual abnormality. This work supports the view that hepatic abnormalities caused by biliary obstruction do not recover quickly following its relief. DISIDA kinetics can quantitate both major and minor degrees of hepatic dysfunction, and may prove to be a valuable method to quantitative liver function.

Animals↗

PubMed1989

Splenectomy for hematologic disease.

Splenectomy has a major role in the treatment of hematologic diseases. Although it is rarely curative, splenectomy removes the site of the destruction or sequestration of erythrocytes, leukocytes, and platelets. Destruction occurs in such diseases as hemolytic anemia and ITP, whereas sequestration occurs as an idiopathic disease or secondary to a host of other diseases described above. Splenectomy is also indicated for symptomatic splenomegaly associated with leukemia, lymphoma, or myeloproliferative disorders. It is palliative, increasing the comfort of the patient by removing a massive spleen. Splenectomy also serves as a staging tool in lymphoma, Hodgkin's disease, and NHL, although it is much more beneficial in Hodgkin's disease, owing simply to stage at presentation. Splenectomy can be performed safely with minimal risk in most patients, but certain diseases carry increased risks of fatality and complications. Such diseases include leukemia, lymphoma, and myeloproliferative disorders, but even in these, splenectomy may be indicated in a select group of patients. The decision to perform splenectomy should therefore be made individually in these cases. Because it can be palliative in some cases, splenectomy can play a role in patient management, even though it may not alter survival.

Hematologic Diseases↗

PubMed1989

Gastrinoma: the predictive value of preoperative localization.

In the management of gastrinoma, a variety of preoperative tests for tumor localization are recommended. Their value in predicting surgical outcome is not well defined. We reviewed the preoperative investigation and operative outcome in 23 patients to assess the predictive value of localization before surgery. With results of laparotomy used as reference, the efficacy of computed tomography, angiography, ultrasonography, and magnetic resonance imaging, individually and combined for primary and metastatic disease, was determined. All investigative modalities were poor for the detection of primary gastrinomas, with individual sensitivities in the range of 20% to 29%. Their combined sensitivity was 53%, with a negative predictive value of only 38%. The detection of metastatic disease was better, with a combined accuracy of 83%. At laparotomy, tumor was identified in 19 of 23 (83%) patients. In 14 patients with negative preoperative workup, primary gastrinoma was found in 10 of 14 (71%) and resected for long-term cure in three of 14 (21%) patients. In all nine patients with positive preoperative test results, tumor was found and was resected for cure in four (44%) patients. In conclusion, preoperative localization of primary gastrinoma is unreliable, and a negative workup does not preclude cure. Therefore, despite the availability of effective palliative antiulcer therapy, all patients exclusive of those with multiple endocrine neoplasia, type I, or metastasis should undergo laparatomy with curative resection in mind.

Angiography↗

PubMed1988

Pharmacokinetic studies of DISIDA disposition. I. Animal studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.

Animals↗

PubMed1988

Pharmacokinetic studies of DISIDA disposition. II. Clinical studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.

Adult↗

PubMed1988

Control of gastrin release in cultured gastrinoma-derived G cells.

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

Early surgical treatment of gastrinoma.

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Duodenal Neoplasms↗

PubMed1987

Role of peptide radioimmunoassay in understanding peptide-peptide interactions and clinical expression of gastroenteropancreatic endocrine tumors.

Peptide radioimmunoassay has become an important clinical and research tool in understanding the role of peptides in the pathophysiology of gut endocrine tumor syndromes. A gut peptide radioimmunoassay laboratory has been established for the diagnosis and clinical monitoring of endocrine tumors of the gastroenteropancreatic (GEP) system. Radioimmunoassay has enhanced our awareness that co-occurring peptide interactions may modify and ultimately influence the clinical expression of these tumors. Furthermore, it has helped develop a rationale for the use of prototype peptides such as somatostatin and its long-acting analogue Sandostatin (SMS 201-995) in the management of GEP tumors. This group's experience, as well as the experience of other investigators, is presented, and the clinical utility of peptide radioimmunoassay in the field of gut endocrinology is demonstrated.

Adult↗

PubMed1987

Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma.

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.

Aged↗

PubMed1986

Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995).

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.

Adult↗