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Biomedical subjects

T R Gadacz

Publications and source records attributed to T R Gadacz.

At least 55 records · Page 3Linked to original sources

Bile salt binding by maalox, sucralfate, and meciadanol: in vitro and clinical comparisons.

Inhibition of gastric acid secretion is a major factor in protecting the gastric mucosa, although other mechanisms such as bile salt binding may contribute to the protective properties of individual agents. Sucralfate, antacid (Maalox), and Meciadanol, a new flavonoid, were compared with cholestyramine resin for binding bile salts. The free, glycine, and taurine conjugates of the human bile salts, cholate, chenodeoxycholate, and deoxycholate, were incubated with each of the above. Cholestyramine resin adsorbed 91-97% of all bile salts tested. Meciadanol adsorbed all of the bile salts fairly well except for the free forms of chenodeoxycholate and deoxycholate. Meciadanol (53 to 84%) adsorbed bile salts better than sucralfate (4.2 to 61%), and significantly (P less than 0.05) better than Maalox (10 to 47%). In our in vitro studies, sucralfate was not as effective in binding bile salts as previously reported. Patients in the surgical intensive care unit were randomized prospectively to receive nasogastric instillation of Maalox, sucralfate, or Meciadanol to prevent gastrointestinal bleeding. The gastric aspirates were analyzed for bile salt concentration. The mean bile salt concentration of those treated with Maalox (0.24 mM), Meciadanol (0.24 mM), or sucralfate (0.35 mM) was significantly lower than those treated with nasogastric aspiration (0.87 mM) alone (P less than 0.01). This suggests that these substances bind bile salts and may provide additional protection to the gastric mucosa along with their ability to neutralize gastric acid.

Adsorption↗

Porcine model for the development of interventional techniques in the gallbladder.

A technique that permits repeated access to the porcine gallbladder through a surgically placed 18 French latex catheter is described and experience with this system in 22 swine is discussed. This porcine gallbladder model produces a reliable and reproducible means for studying clinically applicable interventional procedures.

Abdominal Muscles↗

Quantitative infrared spectroscopy of common bile duct gallstones.

The aim of this study was to determine the composition of gallstones from the common bile duct of patients from the United States and the relationship of stone type to the time interval after cholecystectomy. We analyzed 56 sets of common bile duct gallstones collected over a 10-yr period using infrared and atomic absorption spectroscopy and chemical methods. Twenty-four sets (43%) of stones were cholesterol stones containing 85.3% cholesterol, 3.2% pigment, 0.6% phosphate, and 1.3% total calcium. Ten sets (18%) were black pigment stones containing 36.5% pigment, 11.4% cholesterol, 7.6% carbonate, 3.0% phosphate, and 6.2% total calcium. Twenty-two sets (39%) were brown pigment stones containing 52.7% pigment, 16.5% calcium palmitate, 10.1% cholesterol, 0.4% phosphate, and 3.4% total calcium. Most of the 26 stones found at the same time as or within several months after cholecystectomy were either cholesterol (69%) or black pigment (19%). In contrast, the majority (59%) of the 22 common duct stones that were diagnosed greater than or equal to 21 mo after cholecystectomy were brown pigment stones. In conclusion, brown pigment stones are a distinct type of pigment stone characterized by their content of substantial amounts of calcium palmitate. They comprise a significant proportion of common duct stones in this series of United States patients, particularly of those found greater than or equal to 21 mo after cholecystectomy.

Calcium Carbonate↗

Adjuncts and modifications to basket retrieval of retained biliary calculi.

Although current techniques for percutaneous biliary stone extraction are highly successful, many patients require manipulation of the calculi before such extraction is possible. This article describes several adjunctive techniques for biliary stone retrieval that have proven to be effective. These include the modification of angiographic catheters for catheterization of ipsilateral ducts from the transhepatic approach, extractions of calculi from smaller ducts using constant irrigation and balloon catheters, and balloon-aided transampullary expulsion.

Bile Duct Diseases↗

Agents for gallstone dissolution.

Numerous methods are presently available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin and methyl tert-butyl ether; calcium or pigment solvents such as EDTA and polysorbate; mechanical extraction techniques through a T-tube tract or after endoscopic sphincterotomy; or fragmentation methods such as ultrasonography or electrohydraulic lithotripsy, lasers, and extracorporeal shock waves. Which, if any, of these methods will be appropriate for an individual patient depends on the type of stones, whether they are in the gallbladder or bile ducts, whether access to the biliary tree is available, the patient's age and general medical condition, and the availability of expert radiologists, endoscopists, and newer equipment. In the United States, the only available oral bile salt for cholesterol gallstone dissolution is chenodeoxycholate. Ursodeoxycholate, which is more rapid and less toxic, has not been approved by the Federal Drug Administration. These agents are most effective in thin women with small, floating, radiolucent cholesterol gallstones in a functioning gallbladder. Only about half of this small subset of patients, however, will experience partial or complete dissolution of stones in 6 to 12 months. Moreover, recurrence is very likely, and the potential toxicity of long-term therapy is unknown. Thus, for most patients, cholecystectomy remains the most cost-effective and, perhaps, safest option. Intragallbladder instillation of methyl tert-butyl ether and extracorporeal shock wave therapy are also likely to be applicable to only small subsets of patients and to be associated with high recurrence rates. In patients with retained ductal cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be begun as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90 percent success rate with mono-octanoin infusion can be expected within a week. Radiologic or endoscopic extraction techniques require maturation of a relatively straight T-tube tract but are not dependent on the type of stone. In the hands of experts, these techniques are highly successful. In postcholecystectomy patients without access to the biliary tree, endoscopic sphincterotomy has become the preferred method of management and can be expected to succeed in more than 90 percent of patients. At this point, the exact role for ultrasonic or electrohydraulic lithotripsy and lasers is unknown. However, these techniques may be applicable in the future in patients with retained bile duct stones in whom extraction and infusion techniques have failed.

Administration, Topical↗

The significance of gastric bile reflux seen at endoscopy.

We evaluated the significance of bile seen in the stomach at the time of endoscopy. Twenty-three percent of 110 consecutive patients undergoing elective panendoscopy were found to have bile in their stomachs. Gastric biopsies were obtained from these patients. To assess the significance of bile reflux, the patients underwent a quantitative gastric bile analysis on two separate days. On day 1, gastric juice was aspirated by nasogastric suction, and bile acid concentrations were measured. On day 2, bile reflux into the stomach was quantitated by scintiscan measurement of gastric nucleotide after intravenous administration of 99mTc-DISIDA. Approximately half the patients with bile reflux showed histologic evidence of mucosal injury. However, fewer than half with histologic injury had significant bile reflux when measured by quantitative methods. There was no correlation among the gastric bile acid concentration, degree of histologic injury, or severity of endoscopic changes. We conclude that finding bile reflux at endoscopy is probably of no clinical significance.

Bile Reflux↗

Bile salt malabsorption in pancreatic insufficiency secondary to alcoholic pancreatitis.

Twenty patients with exocrine pancreatic insufficiency secondary to alcohol abuse were studied for the presence of bile salt malabsorption. Fecal bile salts and fecal fat excretion were determined in 15 patients receiving pancreatic enzyme therapy, not receiving enzyme therapy, and on a regimen of pancreatic enzymes plus cimetidine. Serum bile salt levels were measured during fasting and postprandial conditions both during enzyme therapy and after it was stopped in 8 cases. In addition, 5 patients underwent [14C]cholylglycine breath testing during and after discontinuation of enzyme therapy. The fecal bile salt excretion varied between 610 and 3460 mg/day in the untreated patients. Treatment with pancreatic enzymes was associated with significant (p less than 0.05) reduction in fecal bile salt and fecal fat excretion. Cimetidine therapy in addition to enzyme therapy further reduced steatorrhea but failed to alter bile salt excretion significantly. Serum cholylglycine level showed significant (p less than 0.05) postprandial increase in patients receiving enzyme therapy, suggesting improved bile salt absorption. These data suggest a wide range of bile salt malabsorption in alcoholic patients with pancreatic insufficiency, which improves with pancreatic enzyme therapy.

Adult↗

Splenic abscess.

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Abscess↗

Transhiatal (blunt) esophagectomy for malignant and benign esophageal disease: clinical experience and technique.

"Blunt" transhiatal esophagectomy was performed in 23 selected patients. Nineteen had squamous carcinoma of the esophagus (upper third, 1; middle third, 12; distal third, 6), and 2 had adenocarcinoma of the distal esophagus. The other 2 patients had severe lye strictures. Resection with reconstruction was performed in one stage. Esophagogastric continuity was restored using the stomach in the posterior mediastinal position in 20 patients and in the substernal position in 2. The colon in the posterior mediastinal position was used in 1 patient with a lye stricture. Transmural tumor extension or cervical or celiac nodal metastases or both were present in 18 of 21 patients with carcinoma. There was 1 hospital death due to pericardial tamponade. Morbidity included a transient cervical anastomotic leak in 3 patients, one temporary and three permanent unilateral recurrent laryngeal nerve palsies, one intraoperative splenic injury, and severe hemorrhage requiring sternotomy for control in 1 patient. Pulmonary complications occurred in 4 patients: aspiration pneumonia (1) and moderate atelectasis (3). Three patients have died (11, 12, and 17 months postoperatively) in the group with cancer, with follow-up time of 3 to 30 months (mean, 15 months). Transhiatal blunt esophagectomy is a safe and effective procedure in many patients with either esophageal cancer or extensive, benign esophageal strictures.

Adenocarcinoma↗

Ultrasonic fragmentation of gallstones in vitro.

With a Wolf Ultrasonic lithotrite, gallstones from 12 patients were fragmented in vitro. The average fragmentation time was 20 seconds compared with 4 days when they could be dissolved by monooctanoin. A stone from one patient could not be fragmented successfully. The ability of ultrasound to fragment gallstones did not depend on their cholesterol content. Ultrasonics may have an important role in the treatment of biliary stones, especially pigment stones.

Cholelithiasis↗

Comparison of antacids on the binding of bile salts.

Following a gastric operation (and occasionally in other patients), biliary reflux may damage the stomach mucosa. If severe damage occurs, a diverting Roux-en-Y procedure may be required. In most cases, nonoperative treatment is successful. Since bile salts have been implicated as a cause of mucosal injury, we evaluated the efficacy of antacids in binding these salts. Several bile salts were mixed with certain antacids and with cholestyramine resin, and the adsorption was determined. Cholestyramine resin absorbed 90% to 97% of the bile salts. At a pH of 7, magaldrate (Riopan) absorbed the dihydroxy-bile salts as well as cholestyramine resin, but the other antacids we tested showed poor adsorption. The ability of antacids to bind bile salts must be considered when treating bile salt-induced injury with these substances.

Adsorption↗

Prevalence and natural history of distal common bile duct stenosis in alcoholic pancreatitis.

Distal common bile duct stenosis was observed in 16 (9%) of 170 alcoholic patients admitted to a Veterans Administration Medical Center in the last five years. The following clinical and biochemical features were significantly more common (P less than 0.05) among the 16 patients with common bile duct stenosis than in 154 without: jaundice, cholangitis, hyperbilirubinemia, alkaline phosphatasemia, pancreatic calcification, and malabsorption. Surgical decompression of biliary tree was necessitated in 13 of 16 cases due to obstructive jaundice in seven, cholangitis in four, portal fibrosis in one, and persistent abdominal pain in one. The mean (+/- SE) time interval between initial serum alkaline phosphatase elevation and surgical intervention was 308 +/- 108 days. Liver histology in eight cases was remarkable for portal fibrosis in seven and biliary cirrhosis in one. These data suggest that distal common bile duct stenosis is a progressive lesion which is quite prevalent in patients with advanced pancreatic disease of alcoholic etiology.

Alcoholism↗

Toxic effects of intrahepatic reflux of monooctanoin in a canine model.

Monooctanoin (MO), when infused into the common bile duct (CBD), is an effective agent in dissolving retained CBD stones. If the stone migrates and obstructs the distal CBD, the solution could be infused under pressure resulting in intrahepatic reflux. The relationship between the infusion pressure and the safety of monooctanoin has not been evaluated. To study the effects of intrahepatic reflux of MO, a canine model was used and solutions were infused into an obstructed CBD under controlled pressure. Solutions of normal saline (NS), 150 mM sodium cholate (Ch), or MO were infused under pressures of 30, 40, and 50 cm. All of eight dogs died when infused with MO at 50 cm pressure with a mean administered dose of 1.4 +/- 0.4 cc/kg within a mean time of 87 +/- 38 min. Three of four dogs died at 40 cm pressure (1.7 +/- 0.4 cc/kg; 133 +/- 95 min) and only one of three dogs died at 30 cm pressure (2.5 cc/kg; 335 min). These dogs died from progressive hypoxia, acidosis, hemolysis, and hemorrhagic pneumonitis. Four dogs each were administered Ch at 50 and 40 cm pressure and all died with an average absorption of 19 cc/kg. Six dogs were tested with NS at 50 cm and all survived despite absorbing 180 cc/kg in 6 hr. MO at 50 cm pressure and Ch at both 40 and 50 cm pressure were significantly more toxic than saline. It is concluded that MO and Ch infused under pressure into CBD carry a significant risk of serious side effects. The infusion pressure must be monitored to prevent increased biliary pressure which might lead to intrahepatic reflux.

Animals↗

Primary aortoduodenal fistula: manifestation, diagnosis, and treatment.

Primary aortoduodenal fistulas are an especially lethal part of the spectrum of arterioenteric fistulas. The lethal nature is due to the subtleties in manifestation, leading to delays in diagnosis and institution of prompt operative repair. A review of the 118 primary aortoduodenal fistulas in the world's literature reveals that pain (32%), palpable abdominal mass (25%), and bleeding (64%) are inconsistently present as initial symptoms and that routine abdominal films, barium studies, and endoscopy have been ineffective as diagnostic aids. Attention is called to the importance of recognizing the "herald bleed." Operation is usually undertaken emergently and has been successful in only 21 cases in addition to the case reported here. Repair of the duodenal rent and replacement of the aorta with a Dacron prosthesis, rather than an extra-anatomic bypass, is advised.

Abdomen↗

Impairment of human lymphocyte function by bile salts.

Since there appears to be an association between depressed lymphocyte function and liver disease, the effect of bile salts on lymphocyte function was determined in vitro. Peripheral lymphocytes from normal volunteers were incubated with varying concentrations of three bile salts (chenodeoxycholate, deoxycholate, or ursodeoxycholate) and stimulated by the mitogens phytohemagglutinin or concanavalin. The three bile salt concentrations used in these experiments were 75, 100, and 250, mumol/L, which are similar to serum levels found in various types of liver disease. Blast transformation, as measured by tritiated thymidine incorporation, was significantly depressed by all three bile salts at all concentrations and with both mitogens. Suppression increased with the higher bile salt concentrations. However, ursodeoxycholate suppressed lymphocyte function significantly less than did either chenodeoxycholate or deoxycholate. These data suggest that elevated serum bile levels associated with liver disease may contribute to immunosuppression and that ursodeoxycholate, an epimer of chenodeoxycholate that is used for gallstone dissolution, depresses lymphocyte function significantly less than does chenodeoxycholate.

Bile Acids and Salts↗

Tauroursodeoxycholic acid is less damaging than taurochenodeoxycholic acid to the gastric and esophageal mucosa.

Bile acids are capable of disrupting the gastric and esophageal mucosal barriers and are known to differ in their ability to injure these mucosae. Two bile acids, chenodeoxycholic and its 7-B epimer, ursodeoxycholic, that are being used to dissolve gallbladder stones were evaluated for their damaging effects on experimental preparations of the esophageal (rabbit) and gastric (dog) mucosa. Damage was assessed by measuring indices of mucosal barrier function, including net acid flux, potential difference, and tissue resistance, before and after exposure to the taurine conjugates of these bile acids. In both the esophageal and gastric mucosa, tauroursodeoxycholic acid caused significantly less disruption of barrier function than taurochenodeoxycholic acid. These results demonstrate that minor differences in conjugated bile acid structure can cause major changes in the effects of bile acids on the upper gastrointestinal mucosa and that ursodeoxycholic acid may be the preferred bile acid for oral ingestion to dissolve gallbladder stones.

Animals↗

Bile absorption occurs during disruption of the esophageal mucosal barrier.

The role of bile salt absorption in bile-induced disruption of the esophageal mucosal barrier was determined using the continuously perfused rabbit esophagus model. Mucosal barrier disruption was determined by measuring net flux of hydrogen ion, potassium, and glucose. Bile salt absorption was measured by determining net flux of radiolabeled bile salt solution using liquid scintillation counting. Bile salt-containing solutions were prepared with varying concentrations of two bile salts, taurocholate and deoxycholate. The pH of the bile salt exposure also was varied to vary the extent of mucosal injury. The results show that changes in bile salt concentration and in pH of exposure were associated with significant differences in both extent of mucosal barrier disruption and bile salt absorption. Bile salt absorption was associated by direct linear correlation with each index of mucosal barrier function studied. These findings suggest that bile salt absorption plays a role in bile-induced disruption of the esophageal mucosal barrier.

Absorption↗

Exogastric leiomyosarcoma with ultrastructural analysis.

A 50-year-old man was found to have a large exogastric leiomyosarcoma during exploratory laparotomy for a bleeding duodenal ulcer. Although the tumor appeared grossly malignant and was associated with small bowel metastases, its light microscopic appearance was relatively benign. Electron microscopy helped to established the diagnosis of gastric leiomyosarcoma.

Duodenal Ulcer↗