PubMed Health⌕ Search

Biomedical subjects

C F Gholson

Publications and source records attributed to C F Gholson.

At least 37 records · Page 2Linked to original sources

A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer.

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.

Adenocarcinoma↗

Closure of a controlled biliary fistula complicating partial cholecystectomy with endoscopic biliary stenting.

An elderly woman presented 2 months after partial cholecystectomy performed for gangrenous cholecystitis with choledocholithiasis and a controlled biliary fistula. Despite ductal clearance of stones via endoscopic retrograde sphincterotomy and stone extraction, bilious drainage via the fistulous tract persisted. Endoscopic insertion of a 10F Amsterdam endoprosthesis resulted in complete closure of the fistula within 6 wk. This case represents the first example of closure of a biliary fistula after partial cholecystectomy.

Aged↗

Endoscopic retrograde sphincterotomy in swine.

Endoscopic retrograde sphincterotomy was performed on four sedated pigs, ages 3-4 months, using a standard human duodenoscope and papillotome. Sphincterotomies, 1 cm in length, were well-tolerated, and all animals recovered promptly, spontaneously regained gastrointestinal function, and gained weight. The first three animals were sacrificed after one week, and autopsy revealed no complications. The fourth animal was sacrificed immediately following the procedure, and no evidence of perforation was found. These observations demonstrate that the pig is a valid experimental model for endoscopic sphincterotomy. Its use in training is limited by technical and anatomic differences from humans. Potential uses of this technique in research are discussed.

Animals↗

Obstructive jaundice. Nonsurgical options for 'surgical' jaundice.

The development of nonoperative methods of biliary drainage has altered traditional concepts regarding management of medical and surgical jaundice. Patients with newly diagnosed obstructive jaundice typically are elderly and have an unresectable neoplasm. Because surgical cure is often impossible and operation is usually risky in such patients, decompression of the biliary tree by endoscopic retrograde cholangiopancreatography and endoscopically inserted biliary stents has become an increasingly popular means of palliation. Percutaneous transhepatic cholangiography and surgical bilidigestive bypass remain important alternatives. Selection of optimal management for the individual patient requires an in-depth evaluation by a skilled team consisting of the primary care physician, endoscopist, interventional radiologist, and surgeon.

Aged↗

Incidental microvesicular steatosis due to valproic acid anticonvulsant therapy.

Valproic acid has been implicated in at least 100 cases of fatal acute liver failure. Most cases have occurred in patients less than 10 yr old; however, at least seven have involved adults. Microvesicular steatosis has been uniformly observed, but its incidence in less severe liver disease and in asymptomatic patients receiving valproate is unknown. We report two patients receiving maintenance valproate, one with resolving acute hepatitis C and the other with chronic persistent hepatitis C, with incidental microvesicular steatosis demonstrated on oil-red O stains. We conclude that microvesicular steatosis does not necessarily signify hepatotoxicity in patients on chronic valproic acid, and should not lead to discontinuation of the drug until other causes of acute or chronic liver disease have been excluded.

Adult↗

Cell surface expression of hepatitis B surface and core antigens in transfected rat fibroblast cell lines.

Hepatocellular necrosis during hepatitis B virus infection is hypothesized to result from host immune responses against either hepatitis B surface antigen or hepatitis B core antigen expressed on the surface membrane of infected hepatocytes. To study the capacity of hepatitis B deoxyribonucleic acid to induce membrane expression of either hepatitis B surface antigen or hepatitis B core antigen in vitro, we assessed transfected rat fibroblast cell lines by indirect immunofluorescence. Rat fibroblasts were transfected with plasmid vectors containing the natural promoters, native enhancer, and uninterrupted sequences of either the Pre S/S gene or core gene. Resulting cell lines produced hepatitis B surface antigen and hepatitis B core antigen/hepatitis B e antigen, respectively. Immunofluorescence microscopy or flow cytometry showed that hepatitis B surface antigen and hepatitis B core antigen were expressed in a granular pattern in the surface membrane of transfected cells. We conclude that surface membrane expression of both hepatitis B surface antigen and hepatitis B core antigen is an intrinsic consequence of expression of either the Pre S/S or core gene.

Animals↗

Hepatologic considerations in patients with parenchymal liver disease undergoing surgery.

Patients with liver disease requiring surgical procedures are at increased perioperative risk. In addition, the deleterious effect of anesthesia on hepatocellular function, altered drug pharmacokinetics, aberrant hemostasis, postoperative encephalopathy and infection, with multiorgan failure, all contribute to perioperative morbidity and mortality. Although limited by the lack of widely accepted quantitative liver function tests, preoperative evaluation and risk assessment is imperative. Acute viral hepatitis, alcoholic hepatitis, refractory coagulopathy, Child's class C cirrhosis, and emergent surgery are major risk factors predictive of a poor outcome. In addition, elective abdominal surgical procedures should be avoided in potential candidates for orthotopic liver transplantation. Identification and correction of reversible risk factors via meticulous preoperative definition of the etiology, chronicity, and severity of the patient's liver disease within the confines of surgical urgency is the goal of the preoperative hepatology consultation.

Humans↗

Fulminant hepatic failure associated with intravenous erythromycin lactobionate.

Fatal fulminant hepatic failure accompanied by brisk hemolysis developed in an elderly man after intravenous administration of erythromycin lactobionate for a lower respiratory infection. To our knowledge, this is the first case of fatal hepatotoxicity associated with intravenous erythromycin therapy. Erythromycin should be added to the list of drugs that can cause fulminant hepatic failure.

Aged↗

Steroid-responsive chronic hepatic graft-versus-host disease without extrahepatic graft-versus-host disease.

A 29-yr-old woman developed severe, progressive cholestasis 5 months after allogeneic bone marrow transplantation. Extrahepatic graft-versus-host disease (GVHD) was absent. Skin biopsy was equivocal 2 months after transplant, rash was absent during the period of cholestasis, and cholangiographic abnormalities were absent. Liver biopsy 7.5 months posttransplant revealed chronic hepatic GVHD. Cholestasis dramatically resolved with high dose corticosteroid therapy. Chronic hepatic GVHD occurs in the absence of overt extraintestinal GVHD and respond promptly to therapy. This underscores the importance of aggressive diagnostic evaluation of posttransplant cholestasis.

Adult↗

Esophageal perforation after fiberoptic variceal sclerotherapy.

Our experience and review of the literature suggests that perforation follows fiberoptic sclerotherapy at an incidence of 1-6% per patient. Perforation is delayed for 2-14 days after the procedure and is due to chemical necrosis of the esophageal wall. The risk of perforation is higher in Child's class C patients. The use of large volumes or high concentrations of sclerosant may increase the risk of perforation. To reduce this risk, we suggest a cautious approach to Child's class C patients, with no more than two sclerosis sessions during the first 2 weeks of treatment using less than or equal to 10 ml of 1.5% sodium tetradecyl sulfate per session.

Adult↗

Traumatic pancreatitis in a patient with pancreas divisum: clinical and radiographic features.

A previously healthy patient with chronic hyperamylasemia and epigastric pain following blunt abdominal trauma complicated by retroperitoneal hematoma is reported. Endoscopic retrograde cholangiopancreatographic and computerized tomographic examinations revealed pancreatographic characteristics of pancreas divisum with traumatic disruption of the duct of Santorini and adjacent pseudocyst formation. Distal pancreatectomy with cystjejunostomy resulted in total recovery. This represents the first documented case of traumatic pancreatitis in a patient with pancreas divisum.

Adult↗