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Biomedical subjects

K D Lindor

Publications and source records attributed to K D Lindor.

At least 127 records · Page 7Linked to original sources
PubMed1991

The metabolic bone disease of primary sclerosing cholangitis.

The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis.

Adult↗
PubMed1991

The combination of prednisone and colchicine in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract. The cause of the disease is unknown, and no effective medical treatment exists. In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid). Their course was compared with that of a group of concurrent historical controls. At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls. At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients. Analysis of serial liver biopsies showed no differences in histologic change in the two groups. During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group. Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites. In contrast, in the treated group, ascites and bleeding developed in only one patient. We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy. There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment. On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease.

Adult↗
PubMed1990

A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis.

Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation.

Alanine Transaminase↗
PubMed1990

Advances in primary sclerosing cholangitis.

Primary sclerosing cholangitis is an increasingly recognized chronic cholestatic liver disease. It frequently occurs in association with chronic ulcerative colitis and is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. The cause is unknown, although many mechanisms have been considered, including infectious, toxic, and immunologic. The prognosis varies. No adequate treatment exists, although a number of potential treatments have been evaluated in uncontrolled trials, and the results of controlled trials have only recently been reported. Liver transplantation has recently been shown to be an effective treatment for end-stage disease. These various advances in our understanding of primary sclerosing cholangitis are reviewed.

Cholangitis, Sclerosing↗
PubMed1990

Diminished survival in asymptomatic primary biliary cirrhosis. A prospective study.

Data from 73 asymptomatic patients with primary biliary cirrhosis were analyzed to determine clinical course and long-term survival. Of these, 44 entered a D-penicillamine treatment trial; 29 qualified but chose not to participate. Median follow-up was 7.6 yr (range, 2.8-12.2 yr). Liver biopsy at the initial visit showed advanced disease (fibrosis, cirrhosis) in 61% of the patients. During prospective clinical follow-up, which was available for 37 of the 44 study patients, one or more symptoms of liver disease developed in 33 (89%); esophageal varices were found in 15 (41%), and histologic progression to cirrhosis was found in 20 (67%) of the 30 precirrhotic patients. Significant (p less than 0.01) biochemical progression was reflected by a decrease in mean serum albumin concentrations and an increase in mean serum bilirubin levels in 32 patients followed for 4-6 yr. Survival data were available for all 73 patients; 17 died (11 secondary to liver failure), and 1 underwent liver transplantation. These patients had a 4-fold increase in mortality rate (p less than 0.001) compared with the U.S. population matched for age, race, and sex.

Adult↗
PubMed1989

Poor outcome from peritoneovenous shunts for refractory ascites.

We reviewed in retrospect the records of all patients at our institution in whom peritoneovenous shunts were placed to manage refractory ascites due to chronic liver disease from 1977 through 1986. There was a wide spectrum of underlying liver disease in these 23 patients; most frequent was alcoholic cirrhosis. Five were in modified Child's class A, 14 were in class B, and four were in class C. Fourteen of 23 patients had some complication associated with peritoneovenous shunt placement; clinical consumptive coagulopathy, infection, and gastrointestinal hemorrhage while hospitalized were most frequent. Fifteen of 23 died, 12 while hospitalized or within 1 month of hospitalization. Death in eight patients appeared to be related to shunt placement and was due to sepsis in five, hepatorenal syndrome with an obstructed shunt in one, consumptive coagulopathy in one, and pulmonary edema in one. All modified Child's class C patients, six of seven patients with clinical consumptive coagulopathy, and all patients with a preshunt total bilirubin greater than 3.7 mg/dl died while hospitalized or within 1 month of hospitalization. This review supports studies showing that placement of peritoneovenous shunts for refractory ascites has a high morbidity and mortality in patients with advanced liver disease, and does not support their use in the management of refractory ascites.

Adult↗
PubMed1987

Lymphocyte subsets in primary sclerosing cholangitis.

As an initial step in testing the hypothesis that immunoregulatory abnormalities are important in the pathogenesis of primary sclerosing cholangitis, we determined the number and percentage of lymphocyte subsets in the peripheral blood of 33 patients with primary sclerosing cholangitis. In these patients, when compared with normal and diseased controls, there was a significant reduction in the total number of circulating T cells because of a disproportionate decrease in Leu-2a (suppressor/cytotoxic) cells. This decrease resulted in a significantly increased ratio of Leu-3a to Leu-2a cells. Patients with cirrhosis had significantly higher Leu-3a/Leu-2a (helper/suppressor) ratios than did noncirrhotic patients; both disease groups, however, had ratios that were significantly higher than controls. The number and percentage of B cells were significantly increased. Alterations in the percentage of B cells correlated significantly with histologic stage and concentrations of gamma globulin, serum IgG, and bilirubin. We conclude that these abnormalities are suggestive of a defect in immunoregulation in primary sclerosing cholangitis, which is not secondary to advanced liver disease alone and appears to be independent of chronic ulcerative colitis or obstructive jaundice.

Adult↗
PubMed1987

Intragastric balloons in comparison with standard therapy for obesity--a randomized, double-blind trial.

Intragastric balloons are new but commonly used devices for the treatment of obesity; however, their safety and efficacy have not been established. We report our results of a small, double-blind, randomized trial in which the effectiveness of intragastric balloons was compared with that of conventional medical therapy for obesity. Twenty-two patients, who were 21 to 77% over ideal body weight, were studied. Eleven underwent insertion of an intragastric balloon, and 11 underwent sham procedures. One patient with a gastric balloon withdrew from the study after 3 days. Weight loss at 2 to 3 months in the conventional therapy group averaged 2.8 kg; in the balloon-treated group, the mean weight loss was 5.8 kg (P greater than 0.15). Of the 10 balloons, 8 spontaneously deflated, and 1 was passed in the stools. We noted gastric erosions in five patients and multiple gastric ulcers in one. We conclude that the intragastric balloon was not clearly effective in inducing weight loss, had a high rate of spontaneous deflation, and was damaging to the gastric mucosa. Controlled trials should be done before similar weight-reduction devices are used in routine clinical practice.

Adult↗
PubMed1985

Balloon dilatation of upper digestive tract strictures.

The results of balloon dilatation of upper digestive tract stricture in 111 patients were evaluated. Eighty-eight patients had esophageal strictures and 23 had gastric or pyloric strictures. Thirty-six patients had strictures associated with previous operations. Twenty-two percent of the patients with esophageal strictures had malignancies. Overall, 92% were successfully dilated, with a complication rate of 3%. Follow-up information was available in 95% of patients. Eighty-seven percent of living patients experienced symptomatic improvement, which lasted for a median period of 12 mo. Forty percent required a further procedure during the period of follow-up. We found no difference between esophageal strictures and gastric or pyloric strictures in success rate, complications, or need for further dilatation, although patients with esophageal strictures were more apt to have symptomatic improvement. Postoperative strictures responded as well as nonoperative strictures. Previously dilated strictures in patients with esophageal reflux were managed as successfully as strictures never before dilated. We found balloon dilatation of upper digestive tract stricture to be a safe, effective technique.

Adolescent↗
PubMed1985

Preoperative nutritional status and other factors that influence surgical outcome in patients with Crohn's disease.

Among 124 patients who underwent an elective surgical procedure for Crohn's disease during 1 year at our institution, 16(13%) had postoperative complications, including one death. The risk of developing postoperative complications was inversely related to the concentrations of serum albumin and total iron-binding capacity. The complication rate was 29% among patients with low (less than 3.1 g/dl) serum albumin levels but only 6% among patients with normal albumin levels. Patients were also more likely to experience postoperative complications if they had previously undergone an operation for Crohn's disease, received sulfasalazine, or required an ileostomy. No correlations were noted between postoperative complications and preoperative weight loss or preponderance of Crohn's disease of the colon. The median duration of postoperative hospitalization was 24.5 days for the 16 patients with complications in comparison with only 10 days for patients without complications.

Adolescent↗
PubMed1984

Symposium on upper gastrointestinal motility disorders. Gastric motor disorders: an overview.

Disturbances of gastric emptying are being increasingly recognized as causes of clinical problems such as chronic nausea, vomiting, and abdominal pain. Although much remains to be learned, enough information is available to enable the practicing physician to develop an approach to diagnosis and management of these often difficult problems. We review here relevant physiologic concepts of gastric motor activity during fasting and feeding, as well as its controlling mechanisms. These concepts are then applied to develop a rational classification of gastric motor disorders which incorporates clinical as well as pathophysiologic information. Further, we review pertinent diagnostic studies (including gastric emptying tests, manometry, and electrophysiologic measurements) and therapeutic approaches.

Electrophysiology↗
PubMed1979

Liver function values in adults receiving total parenteral nutrition.

A retrospective review was made of results of conventional liver function tests in adult patients who received fat-free total parenteral nutrition (TPN) for two weeks or longer and who did not have other obvious causes for liver function abnormalities. A "meaningful" increase (greater than or equal 50% increase above baseline pre-TPN value) in SGOT levels was noted in 68% of patients, in alkaline phosphatase levels in 54%, and in serum bilirubin levels in 21% of patients. The median peak values for SGOT, alkaline phosphatase, and bilirubin were 3-, 1.9-, and 0.25-fold above the upper limit of normal, respectively. The median time interval of peak increase for each of the three tests was between 9 and 12 days after TPN was started. Liver biopsy specimens from four patients, taken when liver function values were abnormal, showed pronounced steatosis in three patients and mild periportal cholestasis in the fourth patient. The cause(s) of the elevated liver values is unknown, but possibilities include cellular damage, such as steatosis, and an "overshoot" of enzymes when starved patients are refed.

Adult↗
PubMedDate not supplied

Enhanced autoreactivity of T-lymphocytes in primary sclerosing cholangitis.

Primary sclerosing cholangitis is a chronic, cholestatic liver disease in which immune mechanisms are thought to play a role in the pathogenesis. We have determined the frequencies and functional phenotypes of autoreactive T-lymphocytes in peripheral blood specimens from patients with primary sclerosing cholangitis and healthy adults as an indicator of autoreactivity in primary sclerosing cholangitis. We found a significant increase in the percentage of autoreactive suppressor/cytotoxic T-lymphocytes that become activated in the T-, non-T-autologous mixed lymphocyte reaction in primary sclerosing cholangitis patients (p less than 0.002). Blastogenesis in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients was significantly decreased (p less than 0.02), and the magnitude of the decrease correlated directly with the percentage of activated suppressor/cytotoxic T-lymphocytes (r = 0.56, p less than 0.01). The percentage of autoreactive, suppressor T-lymphocytes was increased in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients (p less than 0.0001); and suppression of mitogen-induced blastogenesis by autologous concanavalin A-treated mononuclear cells was significantly enhanced. These results, which were unrelated to the histologic stage of liver disease and the presence or absence of active colitis, document the presence of an expanded population of T-lymphocytes in the peripheral blood of patients with primary sclerosing cholangitis that became activated on exposure to autologous major histocompatibility antigens in the autologous mixed lymphocyte reaction. We hypothesize that these autoreactive cells may be a marker or may participate as effector cells in cell-mediated autoimmunity in primary sclerosing cholangitis.

Adult↗
PubMedDate not supplied

Clinical and statistical analyses of new and evolving therapies for primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic, progressive, cholestatic liver disease thought to be related to abnormalities in immune regulation. The disease is associated with granulomatous bile duct destruction, cholestasis, hepatic copper overloading and the development of hepatic fibrosis or cirrhosis or both. There have been numerous therapeutic trials evaluating immunosuppressive, antifibrotic and cupruretic agents. Prednisolone, D-penicillamine, azathioprine, colchicine and chlorambucil have been evaluated in controlled clinical trials, and biochemical improvement of liver function has been noted with all of the agents, except D-penicillamine. Improved survival has also been reported in patients treated long-term with azathioprine and colchicine. However, none of the therapeutic agents has been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical and histologic remission as has been reported in patients with autoimmune chronic active hepatitis treated with corticosteroids. Many of the trials did not use a double-blind design, failed to use the "intent to treat" rule or failed to define an objective time to analyze results. Many of the studies involved small numbers of patients with short-term follow-up and thus potentially were inadequate to appreciate drug effects that might be of clinical benefit. Currently, there is no totally effective therapy for primary biliary cirrhosis. We believe that well-designed clinical trials can provide important information to better understand this disease until a totally effective therapy is available. New clinical trials should use well-established methodologic guidelines in study design and well-accepted statistical standards in the analysis and interpretation of results.

Adrenal Cortex Hormones↗
PubMedDate not supplied

The autologous mixed lymphocyte reaction in primary biliary cirrhosis: analysis of activation and blastogenesis of autoreactive T lymphocytes.

Blastogenesis of autoreactive T lymphocytes in the autologous mixed lymphocyte reaction has been shown to be decreased in patients with primary biliary cirrhosis, but the mechanisms underlying this abnormality are not known. To investigate further the abnormal autologous mixed lymphocyte reaction in primary biliary cirrhosis, we measured the activation of autoreactive helper/inducer and suppressor/cytotoxic T lymphocytes concurrently with blastogenesis in 35 patients with primary biliary cirrhosis and 18 healthy controls. Blastogenesis was diminished in autologous mixed lymphocyte reaction cultures from primary biliary cirrhosis patients compared to the control subjects (25,273 +/- 20,259 dpm vs. 36,004 +/- 14,951 dpm, p less than 0.02), but cultures from patients with primary biliary cirrhosis contained significantly increased percentages of activated helper/inducer and suppressor/cytotoxic T lymphocytes: 20.6 +/- 7.9 vs. 15.5 +/- 5.3%, p less than 0.008, and 9.8 +/- 7.8 vs. 5.4 +/- 3.0%, p less than 0.02, respectively. These findings were not related to the histologic stage of liver disease or to the serum bilirubin concentration and were not associated with abnormalities of lymphocyte subsets in fresh peripheral blood specimens. We conclude that the percentage of autoreactive T lymphocytes in autologous mixed lymphocyte reaction cultures from peripheral blood is increased in patients with primary biliary cirrhosis and diminished blastogenesis in autologous mixed lymphocyte reaction cultures is not due to the loss of autoreactive T lymphocytes from peripheral blood. Diminished blastogenesis reflects a diminished proliferative response of activated, autoreactive T lymphocytes in primary biliary cirrhosis. Possible mechanisms that may account for the paradoxical findings of decreased blastogenesis and increased activation of autoreactive T lymphocytes in primary biliary cirrhosis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic, usually progressive, cholestatic liver disease of presumed autoimmune etiology that affects predominantly young and middle-aged women. It is nearly always associated with an antibody directed against a component of the pyruvate dehydrogenase complex located on the inner wall of the mitochondria. The disease is associated with a number of other associated autoimmune disorders. No totally effective medical treatment has been established for the disease, although urosdeoxycholic acid appears promising. Complications of cholestasis such as fat malabsorption and fat-soluble vitamin deficiency should be excluded or corrected when found. Individual patient prognosis varies. Several models for estimating individual patient survival are available. Liver transplantation is recognized as a procedure to extend and improve the quality of life for patients with advanced disease.

Female↗
PubMedDate not supplied

Primary sclerosing cholangitis: evolving concepts in diagnosis and treatment.

Primary sclerosing cholangitis is an increasingly recognized cause of chronic cholestatic liver disease. The etiology is unknown, although a number of immunologic and nonimmunologic factors have been considered. The most important diagnostic findings are diffuse irregularity and narrowing of extrahepatic and intrahepatic bile ducts. The prognosis varies, and a number of relatively unique complications may develop. No adequate treatment exists, although a number of potential treatments have been evaluated. Liver transplantation still remains the most appropriate treatment for end-stage disease. These various topics related to primary sclerosing cholangitis are reviewed.

Bile Ducts, Extrahepatic↗