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Biomedical subjects

K R Falchuk

Publications and source records attributed to K R Falchuk.

At least 19 recordsLinked to original sources

The successful treatment of symptomatic, refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt.

Hepatic hydrothorax is a rare complication of portal hypertension. Conservative therapy may be successful but refractory hepatic hydrothorax is not uncommon. Management of refractory hydrothorax is usually ineffective and can result in a worsened clinical status. Transjugular intrahepatic portosystemic shunts (TIPS) lower portal pressure and have been used in the treatment of refractory ascites. The aim of this study was to determine the efficacy of TIPS in the treatment of symptomatic refractory hepatic hydrothorax. A TIPS was placed in 24 consecutive cirrhotic patients with symptomatic refractory hepatic hydrothorax. Five patients (20.8%) were Child's/Pugh class B and 19 (79.2%) were class C. All had undergone multiple thoracenteses and were hypoalbuminemic. Mean follow-up was 7.2 months (range, 0.25-49 months). Fourteen (58.3%) of 24 patients had complete relief of symptoms after shunt placement and did not require further thoracentesis. Five (20.8%) additional patients required fewer thoracenteses. Five (20.8%) patients developed worsening liver function and died within 45 days. In eight (66.7%) of 12 patients with > or = 60 days of follow-up, the serum albumin increased by a mean of 1.2 g/dL (range, 0.1-2.2 g/dL). The Child's-Pugh score improved in 7 (58.3%) of these 12 patients and two patients improved from class C to class A. These two patients no longer require liver transplantation. This study shows that TIPS can be effective in the management of symptomatic, refractory hepatic hydrothorax. Clinical and laboratory improvement may be seen and liver transplantation may become unnecessary.

Female

The intestinal and liver complications of diabetes mellitus.

Gastroparesis, constipation, diarrhea, and fecal incontinence occur frequently in diabetics with long-standing and often poorly controlled insulin-dependent diabetes. These motor abnormalities of the gastrointestinal tract tend to be associated in these patients with evidence of autonomic neuropathy and other diabetes-related complications such as peripheral neuropathy, nephropathy, and retinopathy. The management of these derangements of motility is generally frustrating and very difficult. The prokinetic agents currently available have fewer side effects than previously used drugs, and have expanded the treatment options for diabetics with motility disorders of the gastrointestinal tract. The treatment of diabetic diarrhea remains aimed at the symptom because the cause is often unknown. The diagnosis of diabetic diarrhea depends on a careful and judicious assessment, which allows for the distinction of this condition from other causes of diarrhea. For example, celiac disease can occur in insulin-dependent diabetics, but it is specifically treated by the elimination of gluten from the diet. In recent years, we have also gained a better understanding of the liver and biliary tree abnormalities that occur in the diabetic. The most common hepatobiliary lesions found in these patients include excessive glycogen deposition, fatty liver, and gallstones. Cirrhosis of the liver can develop in diabetics as a result of progressive fatty steatosis, pericentral hepatic fibrosis, and, at times, central hyaline sclerosis. Future study of the underlying pathogenesis of diabetes may one day allow us to find common threads in the seemingly disparate gastrointestinal and hepatic complications of this disease.

Animals

Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-month update.

OBJECTIVE: To determine the long-term efficacy and safety of low-dose methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Eighty-four-month open prospective trial at a single academic rheumatology center. RESULTS: Twenty-six patients were enrolled in a prospective study of the long-term efficacy of MTX in RA; a significant improvement had been demonstrated after 36 months of therapy. Twelve patients remained in the study at the 84-month visit; the mean weekly dosage of MTX was 10.2 mg. A significant improvement was still noted at 84 months in the number of painful joints, number of swollen joints, joint pain index, joint swelling index, and physician and patient global assessments. A 50% improvement in the joint pain index and joint swelling index was observed in more than 80% of the 12 patients still enrolled. A significant reduction in prednisone dosage was achieved; of 14 patients taking prednisone at entry, 7 had discontinued prednisone completely. Fourteen patients withdrew from the study: 10 between 0 and 36 months, and 4 between 36 and 84 months. Toxicity in 3 patients and visit noncompliance in 1 patient were the reasons for withdrawal between 36 and 84 months. At 84 months, 46% of the patients remained in the study; 11.5% had discontinued due to MTX toxicity. CONCLUSION: The effectiveness of MTX in the treatment of RA continues to be demonstrated in this prospective study, after 84 months of treatment.

Aged

Biliary duct stones: update on 54 cases after percutaneous transhepatic removal.

Percutaneous transhepatic removal of common bile duct stones was performed 54 times in 50 patients with a success rate of 93%. In all patients, a modified Dormia basket was inserted through a percutaneous transhepatic catheter, and the stones or fragments were advanced into the duodenum. All patients had contraindications to surgery or had undergone unsuccessful attempts at endoscopic retrograde cholangiopancreatography and sphincterotomy. Monooctanoin (25 patients) or methyl tertiary-butyl ether (four patients) was infused to reduce stone size or remove residual debris. The average time for complete stone removal was 8.6 days. Morbidity was 13% and mortality was 4%, results which compare favorably with those of surgery.

Aged

Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis.

Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression.

Aged

Bile duct stones: percutaneous transhepatic removal.

Percutaneous transhepatic intervention for transduodenal removal of biliary stones was performed 38 times in 34 patients with obstructive jaundice, biliary colic, and cholangitis. The technique entailed the percutaneous transhepatic placement of a modified Dormia basket in the common duct with the flexible tip in the duodenum. The stones were passed into the duodenum and were crushed, or were crushed in the common duct and passed as fragments into the duodenum. In addition to the snare procedure, monooctanoin was used 18 times to dissolve remaining fragments of stone and sludge that could not be snared and passed into the duodenum. The average time for completion of the procedure was 10 days. There were no deaths from the procedure. The complication rate was 21%--probably no greater than would occur with surgery in a similar patient population. The procedure can be performed when endoscopic retrograde cholangiopancreatography and sphincterotomy with stone removal is technically impossible or refused, and in patients who have previously undergone choledochojejunostomy.

Adult

Widespread cytomegalovirus gastroenterocolitis in a patient with acquired immunodeficiency syndrome.

This case report documents extensive gastrointestinal cytomegalovirus infection in a patient with acquired immunodeficiency syndrome, presenting as diarrhea and involving stomach, duodenum, and colon. Endoscopic biopsy specimens and cultures were essential to make the diagnosis and to distinguish the illness from inflammatory bowel disease. A careful search for other potential pathogens was made as well. The discussion includes a review of literature regarding cytomegalovirus involvement of the gastrointestinal tract.

Acquired Immunodeficiency Syndrome

Percutaneous transhepatic removal of common duct stones: report of ten patients.

Ten patients aged 64-94 yr (mean 80 yr) underwent percutaneous transhepatic removal of common duct stones after endoscopic papillotomy and stone removal were judged to be contraindicated. The technique involved percutaneous placement of a modified Dormia basket in the common duct with its tip in the duodenum. The stones or fragments were then snared and carried into the duodenum. In 5 patients monooctanoin infusion was attempted after the basket procedure in order to remove sludge or fragments that resisted snaring or crushing. The stones were 0.5-2.5 cm in diameter. Symptoms disappeared in all 10 patients without further therapy. Complications included an abdominal wall abscess, an unexplained drop in hematocrit, a subcapsular hematoma, and one episode of pancreatitis. All complications resolved without further incident.

Aged

Mutagenicity of N-nitroso bile acid conjugates in Salmonella typhimurium and diploid human lymphoblasts.

Two N-nitroso bile acid conjugates, N-nitrosotaurocholic acid and N-nitrosoglycocholic acid, were tested for mutagenicity by forward mutation assay in Salmonella typhimurium TM 677 and in diploid human lymphoblasts, line TK6. N-Nitrosoglycocholic acid and N-nitrosotaurocholic acid showed similar concentration-response curves in the bacterial assay with statistically significant mutant fractions observed at about 0.12 mM. Nonnitrosated parent compounds were nonmutagenic. However, in the human cell assay, N-nitrosotaurocholic acid gave statistically significant mutant fractions only at 0.4 mM, but N-nitrosoglycocholic acid was mutagenic at 0.05 microM, some 9000 times more potent. Experiments with quantitative Ames' S. typhimurium reversion assays indicated mutagenesis via base substitution.

Cell Line

Nitrite stability and nitrosation potential in human gastric juice.

Human gastric juice samples were investigated from high- and low-risk areas (Colombia and Boston) for factors which influence the stability of nitrite and its potential for nitrosamine formation. The samples from individuals with chronic atrophic gastritis and intestinal metaplasia were not reactive to nitrite and supported a rate of nitrosation largely compatible with the nitrite and thiocyanate concentration. The samples from other individuals contained factors which destroyed nitrite and inhibited nitrosation. There were several samples from both groups which had an elevated rate of nitrosation catalyzed by unknown factors. It is suggested that continued hypochlorhydria might deplete gastric juice of its natural protective factors and lead to an elevated risk of gastric cancer in agreement with our earlier etiological model [1].

Colombia

Intestinal cryptosporidiosis complicated by disseminated cytomegalovirus infection.

A 48-yr-old man with profuse diarrhea for about 9 mo was found to have intestinal cryptosporidiosis. Treatment with antibacterial, antimalarial, and other antiprotozoal agents failed to control the disease. The organisms were identified by light and electron microscopy in a biopsy specimen from the duodenum. Disseminated infection with cytomegalovirus developed during treatment, and the patient died. Five other instances of intestinal cryptosporidiosis have been reported. Immunologic incompetence, related to either disease or therapy, or both, was present in 4 cases but, although suspected, could not be proved in the patient described in this paper.

Adult

Carcinoma of the biliary tree complicating Crohn's disease.

A patient with long-standing Crohn's disease who subsequently developed carcinoma of the biliary tree is described. Biliary tract neoplasia may represent another extraintestinal complication of Crohn's disease, but its frequency of association is probably less than that of ulcerative colitis.

Adenocarcinoma

Pericentral hepatic fibrosis and intracellular hyalin in diabetes mellitus.

Five patients with maturity-onset diabetes mellitus and hepatomegaly were studied. This group in cluded moderately obese females in whom hepatomegaly and abnormal liver studies were associated with a marked elevation in the erythrocyte sedimentation rate. Liver biopsies from all 5 showed fatty steatosis and pericentral fibrosis. In 3 of the 5, fibrous bridging between central veins and portal tracts was present. Collagen surrounded swollen hepatocytes, some of which contained intracellular hyalin indistinguishable from Mallory's hyalin. Polymorphonuclear neutrophils and regenerating nodules were not present. None of the patients had a history of alcohol use, and in 2 followed closely for 2 yr, alcohol was never detected in random blood samples. The recognition of this morphologic lesion may help to clarify the significance of this finding as an intermediate lesion between fatty steatosis and cirrhosis in diabetics.

Adult