Fred B. Thomas

Chenodiol (Chenodeoxycholic Acid) for Dissolution of Gallstones: The National Cooperative Gallstone Study: A Controlled Trial of Efficacy and Safety

A double-masked study was conducted to determine the efficacy and safety of randomly allocated chenodiol (chenodeoxycholic acid, 750 mg/d or 350 mg/d) or placebo administered for 2 years to 916 patients for dissolution of radiolucent gallstones. There was confirmed complete dissolution in 13.5% of patients (750 mg/d), 5.2% (375 mg/d), and 0.8% (placebo), p less than 0.0001. Partial (over 50%) or complete dissolution (by validated roentgenographic metrology) occurred in 40.8% (750 mg/d), 23.6% (375 mg/d), and 11.0% (placebo), p less than 0.0001. Dissolution occurred more frequently in women, thin patients, or patients with small or floating gallstones or serum cholesterol greater than or equal to 227 mg/dL. Clinically significant hepatotoxicity occurred in 3% of patients (750 mg/d), 0.4% (375 mg/d), and 0.4% (placebo), p less than 0.007, and always was reversible biochemically. Elevations of 10% or more of serum cholesterol, mostly low-density lipoproteins, occurred in 85.2% of patients (750 mg/d), 82.8% (375 mg/d), and 67.0% (placebo), p less than 0.001. Chenodiol, 750 mg/d for up to 2 years, is appropriate therapy for dissolution of gallstones in selected patients who are informed of the risks and benefits.

Stimulation of Secretion of Gastric Inhibitory Polypeptide and Insulin by Intraduodenal Amino Acid Perfusion

The effect of intraduodenal or intravenous administration of a 30-gm mixed amino acid solution of serum gastric inhibitory polypeptide (GIP), alpha-amino nitrogen (AAN), glucose, and insulin concentrations was studied in 10 normal subjects. Initially, an intraduodenal amino acid perfusion (15 ml per min X 60 min) was performed in each subject and was followed in 1 to 2 weeks by an intravenous infusion. Peak AAN concentrations occurred at 60 min after both routes of administration, but were greater with intravenous infusion, 145 +/- 5.7 mug per ml vs. 89 +/- 4.4 mug per ml (P less than 0.001). Although serum AAN levels were significantly lower after intraduodenal administration, incremental insulin concentrations were greater after intraduodenal perfusion, 77.3 +/- 8.8 muM per ml vs. 43.1 +/- 5.6 muU per ml (P less than 0.005). Total integrated insulin secretion was also greater after intraduodenal amino acids, 5000 vs. 2400 muU-min ml-1 (P less than 0.005). With intravenous amino acid infusion, serum GIP concentrations remained below the assay detection limit. After intraduodenal perfusion, a mean maximum GIP increment of 468 pg per ml occurred at 15 min. In all subjects peak GIP concentrations occurred at 15 min and preceded the maximum insulin rise by 15 to 30 min. Total integrated GIP secretion was significantly greater after intraduodenal amino acid perfusion, 13,000 pg-min ml-1 vs. no measurable response with intravenous infusion. In separate studies performed in 12 subjects, no significant changes in serum GIP concentrations occurred after intraduodenal perfusion of 0.45% saline, 0.9% saline, or 10% mannitol. The results of this study demonstrate that intraduodenal amino acid administration stimulates the secretion of GIP and suggest that endogenously released GIP may be important in the enteric mediated release of insulin.

Apathetic Thyrotoxicosis: A Distinctive Clinical and Laboratory Entity

Abstract Nine patients with apathetic thyrotoxicosis were studied over a 1-year period and compared with 29 typical hyperthyroid subjects. These apathetic patients were significantly older and had ...

Pretreatment biliary lipid composition in white patients with radiolucent gallstones in the National Cooperative Gallstone Study

Biliary lipid classes (bile acids, phospholipids, cholesterol) as well as individual biliary bile acids were measured in duodenal bile samples obtained before treatment from 284 white men and 264 white women participating in the National Cooperative Gallstone Study. The patients had radiolucent gallstones present in visualizing gallbladders. Calculated biliary cholesterol saturation was significantly higher in women (143 +/- 43, mean +/- SD, vs. 132 +/- 39 for men). Chenodeoxycholic acid was the major biliary bile acid in both sexes (40.0 +/- 9.9 in men; 38.8 +/- 9.3 in women, NS). Cholic acid was the second most common bile acid, constituting 32.9 +/- 8.8 in men and 31.8 +/- 8.9 in women (NS). When other demographic and clinical characteristics, including serum lipids, were related with biliary lipid composition, only percent ideal body weight correlated significantly. The partial correlation coefficient adjusted for percent ideal body weight indicated that the proportion of chenodeoxycholic acid correlated negatively with the mole fraction of cholesterol in bile in men, but not in women. Multiple regression analyses showed that bile saturation could not be predicted reliably from any clinical, chemical, or radiologic measurement in either sex. Published data for biliary lipid composition in individuals with biliary disease showed considerable overlap with the National Cooperative Gallstone Study data reported here, suggesting that cholesterol gallstone disease is not caused solely by increased biliary cholesterol saturation.

Localization of Gastric Inhibitory Polypeptide Release by Intestinal Glucose Perfusion in Man

To determine the site of endogenous release of gastric inhibitory polypeptide (GIP), glucose perfusions (556 mmoles per liter) of duodenum, proximal jejunum, midjejunum, and ileum were performed in human volunteers using an occluding balloon perfusion technique. Preperfusion GIP concentrations were below assay sensitivity (125 pg per ml) in all subjects. After glucose perfusion, maximal serum GIP concentrations for the four groups were: duodenum, 1383 +/- 152 pg per ml; proximal jejunum, 904 +/- 87 pg per ml; midjejunum, 545 +/- 91 pg per ml, and ileum 305 +/- 38 pg per ml. Integrated GIP secretion was significantly greater with duodenal perfusion (111 +/- 21 ng-min ml-1) d proximal jejunal perfusion (69 +/- 5 ng-min ml-1), as compared to either midjejunal (47 +/- 7 ng-min ml-1) or ileal (25 +/- 6 ng-min ml-1) perfusions. Peak serum insulin concentrations and integrated insulin secretion were also significantly greater with perfusion of the duodenum or proximal jejunum. Serum glucose concentrations, integrated serum glucose, and glucose absorption were similar for the four areas perfused. The results of this study indicate that the proximal small intestine is the primary site of endogenous GIP release in man, but that smaller quantities are also released by the distal small bowel.

Low-Dose Chenodiol to Prevent Gallstone Recurrence After Dissolution Therapy

Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.

Pancreatic cystadenoma in Von Hippel-Lindau disease: an unusual cause of pancreatic and common bile duct obstruction.

Pancreatic cystadenoma is an unusual lesion of the pancreas, typically occurring as an isolated lesion in a middle-aged woman with abdominal pain or an asymptomatic epigastric mass. Jaundice is unusual. Two types of pancreatic cystadenoma are distinguished: microcystic and mucinous; the latter has a tendency to malignant degeneration. A patient with Von Hippel-Lindau disease and pancreatic cystadenoma developed jaundice due to common bile and pancreatic duct obstruction. Cystic and adenomatous lesions of the pancreas are common in Von Hippel-Lindau disease, but jaundice due to common bile duct obstruction has not previously been reported.

Kaposi's sarcoma: endoscopic observations of gastric and colon involvement.

Kaposis sarcoma is a multisystem neoplastic disease in which skin manifestations are usually seen first. Visceral involvement is frequent and the gastrointestinal tract is the most common location. We report a patient with Kaposis sarcoma in whom the typical violaceous skin lesions were the sarcoma in whom the typical violaceous skin lesions were the only overt clinical manifestations, but the patient had multiple macular angiodysplastic-like lesions on colonoscopy. In contrast to the uniform appearance of the colonic lesions, polypoid, volcano, and maculopapular lesions were seen in the stomach on endoscopy. This report provides probably the first endoscopic description of the colonic lesions of Kaposis sarcoma and contrasts them with the typical upper gastrointestinal lesions. A thorough gastrointestinal survey should be performed in all patients with Kaposis sarcoma to delineate involvement, since appropriate treatment will be dictated by the presence or absence of visceral involvement.

Yttrium-90 microsphere induced gastrointestinal tract ulceration

BackgroundRadiomicrosphere therapy (RT) utilizing yttrium-90 (90Y) microspheres has been shown to be an effective regional treatment for primary and secondary hepatic malignancies. We sought to determine a large academic institutions experience regarding the extent and frequency of gastrointestinal complications.MethodsBetween 2004 and 2007, 27 patients underwent RT for primary or secondary hepatic malignancies. Charts were subsequently reviewed to determine the incidence and severity of GI ulceration.ResultsThree patients presented with gastrointestinal bleeding and underwent upper endoscopy. Review of the pretreatment angiograms showed normal vascular anatomy in one patient, sclerosed hepatic vasculature in a patient who had undergone prior chemoembolization in a second, and an aberrant left hepatic artery in a third. None had undergone prophylactic gastroduodenal artery embolization. Endoscopic findings included erythema, mucosal erosions, and large gastric ulcers. Microspheres were visible on endoscopic biopsy. In two patients, gastric ulcers were persistent at the time of repeat endoscopy 1–4 months later despite proton pump inhibitor therapy. One elderly patient who refused surgical intervention died from recurrent hemorrhage.ConclusionGastrointestinal ulceration is a known yet rarely reported complication of 90Y microsphere embolization with potentially life-threatening consequences. Once diagnosed, refractory ulcers should be considered for aggressive surgical management.

Spontaneous Bacterial Peritonitis Associated with Acute Viral Hepatitis

Spontaneous bacterial peritonitis (SBP) occurs most frequently in patients with cirrhosis and preexistent ascites; SBP has not been previously recognized in association with acute liver disease. We report two patients with acute hepatitis B infection who developed SBP. Patient 1 had Streptococcus pneumoniae peritonitis and bacteremia, but did not have ascites until after the peritoneal infection was evident. Subsequent liver biopsy and follow-up studies confirmed the clinical diagnosis of acute hepatitis. Patient 2 had sub-massive hepatic necrosis due to hepatitis B and developed ascites before Streptococcus fecalis SBP. Although the association of SBP with acute hepatic injury is rare, these two patients illustrate that the syndrome of SBP does occur with acute liver disease.