Deplores cost/benefit ratio of precertification program.
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Cost-Benefit Analysis↗
Biomedical subjects
L G Halloran
Publications and source records attributed to L G Halloran.
Reconstruction of the bile duct with transanastomotic U tubes.
Thirty-one adult patients have undergone reconstruction of the bile duct using a transanastomotic U tube to stent biliary-enteric anastomoses. The U tube is brought through the substance of the liver into the proximal part of the bile duct, threaded through the anastomosis, usually to a Roux-en-Y limb of jejunum and then withdrawn from the jejunum through a separate enterotomy. Both ends of the Silastic (silicone rubber) catheter are then brought out the abdominal wall through separate stab incisions and secured to the abdominal wall. In 21 patients, the procedure was performed for benign disease. There were no operative deaths. Recurrent strictures developed in two patients (9.5 per cent). There were seven infectious complications, none of which were life-threatening. Preoperative bilirubin levels averaged 9.5 milligrams per cent; postoperative bilirubin levels averaged 2.6 milligrams per cent. Recurrent stricture developed in two patients at 20 and 19 months after removal of the U tubes. In ten patients, the obstruction of the biliary tract was secondary to malignant disease--seven primary tumors of the biliary tract and three metastatic tumors. Operative mortality was 20 per cent. Among the patients who survived the operation, the average bilirubin level was 6.6 milligrams per cent as compared with the average preoperative level of 14.4 milligrams per cent.
Abscess↗
Gastric secretory and mucosal injury response to severe head trauma.
The problem of gastric secretory and mucosal injury response was evaluated in 19 patients who had suffered a severe head injury. Fifteen of 19 patients had some evidence of gastrointestinal hemorrhage. In 7 cases, this was marked. The mean volume of gastric secretions ranged from 36.4 ml/hour on Day 1 to 47.6 ml/hour on Day 6. The mean value of titratable acidity ranged from 3.4 meq/hour on Day 1 to 3.9 meq/hour on Day 6. Possible risk factors were analyzed as a means of predicting specific subgroups of severely injured patients who would be more prone to have gastrointestinal complications. During the first 6 days after injury, there was no significant association (correlation coefficient not significant at the 0.05 level of significance) of the presence of an intracranial mass lesion, elevated intracranial pressure, brain stem dysfunction or prior episodes of hypotension or hypoxia, sepsis, shock, or the requirement for pressor agents with elevated gastric acid output, mucosal erosion, or hemorrhage. Because no specific risk factor or factors could be identified, all severely brain-injured patients should be on some form of therapy for the prevention of gastrointestinal complications.
Adult↗
An in vivo evaluation in man of the transfer of esterified cholesterol between lipoproteins and into the liver and bile.
The metabolism of the esterified cholesterol fractions of HDL and LDL has been studied in vivo in man with regard to their ability to serve as precursors (after intrahepatic hydrolysis) for bile acid synthesis and biliary cholesterol secretion. Information was also obtained on the exchange of cholesterol esters between the lipoprotein classes. Fasting subjects were intravenously administered autologous HDL (or LDL) labeled with esterified [3H]cholesterol and free [3H]- and [14C]cholesterol. Following the administration of the labeled lipoproteins, bile and blood were collected at frequent intervals. In each experiment the observed 3H/14C ratios in bile acids, biliary cholesterol, lipoprotein free cholesterol and red blood cell cholesterol were similar and markedly divergent from the lipoprotein esterified cholesterol 3H/14C ratios. Following the administration of labeled HDL, the 3H/14C ratios observed in the esterified cholesterol fractions of VLDL and LDL closely resembled the ratios in HDL indicating that VLDL and LDL received esterified cholesterol by direct transfer from HDL. Following the administration of labeled LDL, the 3H/14C ratios in HDL esterified cholesterol were midway between the ratio in LDL esterified cholesterol and plasma free cholesterol, indicating that HDL esterified cholesterol is derived from more than one source. These sources could be LDL esterified cholesterol and esters formed de novo from plasma free cholesterol. A precursor-product relationship was found between the specific activities of lipoprotein free cholesterol and the bile steroids. Assuming direct entry of lipoprotein free and esterified cholesterol (after hydrolysis) into the bile acid and biliary cholesterol precursor pools, it was calculated that less than 20% of these biliary steroids could be derived from HDL esterified cholesterol. The results support the view that lipoprotein free cholesterol is the major source of bile acids in man. Also, the results suggest that in vivo esterified cholesterol fractions of VLDL and LDL originate from HDL, that some LDL ester is transferred back to HDL, and that the cholesterol liberated form hydrolyzed esters undergoes recirculation into the free cholesterol pool rather than excretion as biliary cholesterol or bile acids.
Adult↗
Doppler ultrasound facilitates renal vein dissection during distal splenorenal shunt.
We have found that the use of intraoperative Doppler ultrasound greatly facilitates the performance of the selective distal splenorenal shunt by precisely identifying the retroperitoneal location of the renal vein. The amount of dissection and tissue injury required for performing this operation was, thereby, minimized. This may theoretically result in a lowered incidence of postoperative ascites and complications after the Warren shunt.
Doppler Effect↗
Bile acid synthesis in humans.
Metabolic pathways involved in the conversion of cholesterol to cholic and chenodeoxycholic acids have been investigated in bile fistula patients treated with a number of labeled potential bile acid intermediates. The findings of the present report indicate that the human liver cell has the capacity to synthesize both primary bile acids via multiple routes from cholesterol and 7 alpha-hydroxycholesterol. Evidence has been obtained for the existence of a major pathway to chenodeoxycholic acid via the 26-hydroxylation of 7 alpha-hydroxycholest-4-en-3-one. Cholic acid is synthesized preferentially via pathways from 5 beta-cholestane 3 alpha, 7 alpha-diol and a pathway from cholesterol not involving an initial 7 alpha-hydroxylation.
Bile Acids and Salts↗
The effect of prophylactic drainage on subhepatic fluid collections after elective cholecystectomy: a prospective randomized ultrasonographic study.
Seventy-six patients undergoing elective cholecystectomy were randomly divided into drained and nondrained subjects and studied with sonography preoperatively and postoperatively to determine the incidence and fate of subhepatic fluid collections. In the drained group, detectable subhepatic fluid was seen in 5 per cent of patients, whereas it occurred in 20 per cent of nondrained patients. Although this difference achieved statistical significance (P less than 0.05), there were no complications directly attributable to the retained subhepatic fluid. On the contrary, this study supports previous observations that patients undergoing cholecystectomy without drainage have less postoperative fever. Subhepatic fluid collections occurred in a small number of patients so managed but were of no clinical significance in this study.
Adult↗
Biosynthesis of bile acids in man. Multiple pathways to cholic acid and chenodeoxycholic acid.
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Aged↗
Prevention of acute gastrointestinal complications after severe head injury: a controlled trial of cimetidine prophylaxis.
Cimetidine prophylaxis significantly reduced the risk of gastrointestinal bleeding after severe head injury in this prospective, double-blind clinical trial. Cimetidine effectively reduced both the volume and the acidity of gastric secretions after brain injury without producing adverse side effects. The most common endoscopic finding was superficial, erosive, mucosal lesions in the proximal stomach. Cimetidine prophylaxis was not shown to reduce the incidence of these lesions in this study but did diminish their severity and the likelihood that they would complicate the management of these patients.
Adolescent↗
Postoperative appendicitis.
Appendicitis developed in three patients during the postoperative period. At reoperation, perforation of the appendix occurred in all three instances and abscess was present in two. The postoperative status caused confusion in the diagnosis and led to inappropriate delay in operation. Failure to recognize appendicitis in the postoperative period suggests that a higher than normal incidence of rupture can be expected in this patient group.
Abdomen↗
An in vivo evaluation of the quantitative significance of several potential pathways to cholic and chenodeoxycholic acids from cholesterol in man.
The present study was designed to obtain more definitive information in man on the metabolic pathways to chenodeoxycholic acid and to cholic acid via a pathway not involving an initial 7 alpha-hydroxylation of cholesterol. Four bile fistula patients were administered consecutively two or more of the following 3H-labeled bile acid intermediates: 7 alpha-hydroxycholesterol, 7 alpha-hydroxy-4-cholesten-3-one, 5 beta-cholestane 3 alpha,7 alpha,26-triol, 26-hydroxycholesterol,7 alpha,26-dihydroxy-4-cholesten-3-one, and 5-cholestene-3 beta,12 alpha-diol. Both 7 alpha-hydroxy[7 beta-3H]cholesterol and 7 alpha-hydroxy-4-[6 beta-3H]cholesten-3-one were efficiently converted to bile acids and preferred chenodeoxycholic acid over cholic acid. The specific activity time curves indicated that a portion of cholic acid synthesis did not pass through 7 alpha-hydroxycholesterol. [3H]26-Hydroxycholesterol and [3H]-5-cholestene 3 beta,12 alpha-diol, two potential intermediates of this bypass pathway to cholic acid, were poorly converted to primary bile acids (10 to 27%). The [3H]26-hydroxycholesterol preferred chenodeoxycholic over cholic acid by about 4 to 1. The [3H]5-cholestene 3 beta,12 alpha-diol formed cholic acid in low yield (10 to 20%). It is concluded that pathways to primary acids from cholesterol through 26-hydroxycholesterol and 5-cholestene 3 beta,12 alpha-diol are probably of minor quantitative significance. A selective pathway to chenodeoxycholic acid via 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one was also investigated. The 5 beta-cholestane 3 alpha,7 alpha,26-triol was converted in about equal amounts to cholic and chenodeoxycholic acids. The 7 alpha-hydroxy-4-cholesten-3-one was also efficiently converted to both bile acids but preferred chemodeoxycholic acid. The most efficient precursor of chenodeoxycholic acid was 7 alpha,26-dihydroxy-4-cholesten-3-one, which was efficiently converted to primary bile acids; chenodeoxycholic acid was preferred over cholic acid by approximately 7 to 1. These findings suggest the presence of a major pathway to chenodeoxycholic acid via the 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one and intermediate formation of 7 alpha,26-dihydroxy-4-cholesten-3-one.
Bile↗
Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man.
High- and low-density lipoproteins carrying free cholesterol labeled with 3H or 14C were administered to a patient with a bile fistula. The free cholesterol from high-density lipoproteins was more rapidly incorporated into biliary cholesterol than the free cholesterol from low-density lipoproteins. These findings show that the liver in man selectively utilizes and secretes the free cholesterol from a particular lipoprotein.
Aged↗
Multicompartmental analysis of cholesterol metabolism in man. Characterization of the hepatic bile acid and biliary cholesterol precursor sites.
The present report has presented the first clear evidence in man for the existence of specific hepatic cholesterol precursor sites associated with the formation and secretion of bile acids and biliary cholesterol. These hepatic compartments derive virtually all their cholesterol from newly synthesized and lipoprotein free cholesterol. The model which is presented was formulated on current concepts of cholesterol metabolism in man and is concerned, at this initial stage, with the elucidation of the bile acid and biliary cholesterol compartments. The complexity of cholesterol metabolism in man necessitated an initial approach that would minimize the number of inputs of cholesterol into the system, allow for the sampling of several cholesterol compartments, and permit the simultaneous labeling of newly synthesized cholesterol and preformed cholesterol. To achieve these objectives, we studied the patient with a total bile fistula. Six patients were administered simultaneously pulse injections of labeled mevalonic acid and [(14)C]cholesterol. The qualitative features of the specific activity time course curves after labeled mevalonic acid revealed no precursor-product relationship between bile acid, biliary cholesterol, and plasma free cholesterol. The peak specific activity of the bile acids was reached in approximately 100 min and was higher than the biliary cholesterol, which was higher than the plasma free cholesterol. The plasma free cholesterol specific activity became higher than the other lipids after 12 h and remained higher throughout the period of study. Similar related observations were made with [(14)C]cholesterol. The data were then subjected to simulation analysis and modeling using the SAAM-27 computer program. Computer least-square fits of the data were obtained after the model was evolved. During the model development, the least number of compartments and transport pathways were introduced consistent with a good fit of the data. Of particular importance was the constraint that the model fit the data obtained from both [(14)C]cholesterol and labeled mevalonic acid. The same parameter values were used to fit the data from both tracers. The fluxes arrived at in the model indicate that 31% and 20%, respectively, of the cholesterol input into the bile acid and biliary cholesterol precursor sites were derived directly from the newly synthesized hepatic cholesterol. The remainder had its origin predominantly from lipoprotein free cholesterol. Plasma esterified cholesterol (as free) made a small contribution (11%) to the bile acid compartment. Similarly, 10% of the biliary cholesterol arose from an unknown hepatic site. The present report has provided the basis for a new procedure for studying in vivo cholesterol metabolism in man. Examination of the derived cholesterol flux rates between the compartments suggests the presence of an important mechanism regulating the partitioning of lipoprotein free cholesterol between the bile acid and biliary cholesterol precursor sites. Aberrations in the proportioning of precursor cholesterol between these sites could be a causative factor precipitating the excessive secretion of biliary cholesterol and the production of lithogenic bile.
Aged↗
Evidence for high-density lipoprotein-free cholesterol as the primary precursor for bile-acid synthesis in man.
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Aged↗
Cimetidine prevention of gastrointestinal bleeding in severe head injury: a controlled clinical trial.
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Adolescent↗
Duodenal ulcer disease: a fresh appraisal.
There have been remarkable recent advances in knowledge about duodenal ulcer, a disease which may be spontaneously disappearing. Multiple physiologic defects have been found including increased numbers of parietal cells and their increased sensitivity to gastrin, excessive gastrin release after food intake, decreased inhibition of gastrin release by low antral pH, more rapid gastric emptying, and, possibly, impaired duodenal mucosal resistance to acid. Antacid and diet therapies have been subjected to scientific scrutiny and their respective roles in the therapy of the duodenal ulcer are now better defined. New drugs have been developed which strongly inhibit gastric acid secretion in man--the recently marketed histamine H2-receptor antagonist, cimetidine, as well as chemically modified prostaglandins. Clinical trials have shown cimetidine to be effective in healing duodenal ulcers and free of significant side effects with short-term usage. Its role in the prevention of ulcer recurrence is presently being evaluated. A new operation for duodenal ulcer has been introduced which shows great promise following pilot studies and some randomized trials. Only the parietal cell containing portion of the stomach is denervated. Basal and stimulated gastric acid secretion are markedly inhibited while gastric motility is unimpaired. This operation thus eliminates the need for a drainage procedure or distal antral resection and decreases the incidence and severity of undesirable side effects associated with earlier operations for duodenal ulcer.
Antacids↗
Evidence for a common hepatic cholesterol precursor site for cholic and chenodeoxycholic acid synthesis in man.
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Chenodeoxycholic Acid↗
Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man.
The in vivo conversion of several 5 beta-cholestane intermediates to primary bile acids was investigated in three patients with total biliary diversion. The following compounds were administered intravenously: 5 beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3 alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7 alpha-25-triol. Bile was then collected quantitatively at frequent intervals for the next 21 to 28 h. The administered 5 beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently converted to cholic and chenodeoxycholic acids in two patients; 61 and 75% of the administered label was found in primary bile acids. The proportion of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of these patients, indicating that the C-26 triol was efficiently converted to cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha, 7alpha-diol intermediate was also efficiently converted (71%) to both primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and label were similar (2.97 versus 2.23). By contrast, the 5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile acids in three patients. Following the administration of this compound almost all of the administered radioactivity found in the bile acid fraction was in cholic acid (5 to 19%) and very little (less than 5%) was found in chenodeoxycholic acid. These findings indicate that ring hydroxylation at position 12 is not materially hindered by the presence of a hydroxyl group on the side chain at C-26 in patients with biliary diversion. The labeled C-26-triol which was efficiently converted to both primary bile acids in a proportion similar to that which was observed for the bile acids synthesized by the liver suggests that this 5beta-cholestane derivative may be a major intermediate in the synthesis of both cholic and chenodeoxycholic acids.
Bile Acids and Salts↗