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Biomedical subjects

Keith D Lindor

Publications and source records attributed to Keith D Lindor.

61 records · Page 4Linked to original sources
PubMed2002

Sclerosing cholangitis.

Primary sclerosing cholangitis in children can mimic autoimmune hepatitis in the absence of inflammatory bowel disease. Most adult patients have been identified with human leukocyte antigens that either predispose or protect against disease. Novel class I alleles and cytokine polymorphisms may also contribute to disease susceptibility. Primary alpha-hemolytic streptococci infection does not appear to directly cause primary sclerosing cholangitis. Promising diagnostic modalities such as single photon emission tomography require further study in comparison with cholangiographic techniques. Positron-emission tomography and DNA cytometry appear promising for confirming occult cholangiocarcinoma when present. The chemoprevention effects of ursodeoxycholic acid on colorectal dysplasia await further investigation. Initial results from high-dose ursodeoxycholic acid in halting disease progression, however, suggest a beneficial effect. In contrast, the impact of endoscopic therapy on natural history remains unresolved. Although liver transplantation continues to be effective for end-stage liver disease, disease recurrence in the allograft is a controversial topic.

Journal Article↗
PubMed2002

Pregnancy in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome that is characterized by fibrosing inflammatory destruction of intra- and/or extrahepatic biliary ducts. The etiology is unknown and there is no known effective treatment. The course of PSC is quite variable; however, the disease is typically slowly progressive. There is little known regarding the natural history and potential complications of pregnancy in a patient with PSC. This case report details a 36-year-old woman with PSC who became pregnant. The pregnancy was complicated by the development of dominant stricture. A healthy baby boy was delivered at 33.5 weeks. The mother required cholangiography and stent placement immediately after delivery, but her postpartum course was otherwise unremarkable.

Adult↗
PubMed2002

In primary sclerosing cholangitis, gallbladder polyps are frequently malignant.

OBJECTIVE: The management of gallbladder polyps/masses in patients with primary sclerosing cholangitis (PSC) (i.e., cholecystectomy vs observation) remains problematic. Given the risk of biliary tract cancer in PSC in the face of the benign nature of most gallbladder polyps in the general population, our aim was to determine the prevalence of gallbladder cancer in PSC patients with a gallbladder mass who had undergone cholecystectomy. METHODS: The case records of all patients with PSC undergoing a cholecystectomy at the Mayo Clinic between 1977-1999 were reviewed. RESULTS: Of the 102 patients with PSC who underwent a cholecystectomy, 14 of 102 (13.7%) had a gallbladder mass. In the subset of patients with gallbladder masses, eight of 14 (57%) had adenocarcinomas (seven primary adenocarcinomas and one metastatic cholangiocarcinoma); the other six had benign masses (five adenomas and one cholesterol polyp). In those patients with benign masses, 33% had associated epithelial cell dysplasia; in patients with primary gallbladder cancers, 57% had associated dysplasia. The patients with primary gallbladder adenocarcinoma had a favorable outcome after cholecystectomy, with a 36-month survival of 66%. CONCLUSIONS: In conclusion, gallbladder neoplasms in PSC patients are malignant in approximately 40-60% of the cases. The presence of gallbladder epithelial cell dysplasia suggests a dysplasia-carcinoma sequence in PSC similar to that observed in ulcerative colitis. Consideration should be given to performing a cholecystectomy in PSC patients with gallbladder polyps. If a cholecystectomy is not performed, careful interval follow-up is warranted.

Adenocarcinoma↗
PubMed2002

Overlap of autoimmune hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system.

OBJECTIVE: The coexistence of autoimmune hepatitis (AIH) with primary biliary cirrhosis (PBC) as an overlap syndrome has been previously described. The ability to detect AIH overlap with a revised version of the International Autoimmune Hepatitis Group (IAHG) scoring system, however, remains unknown. Our specific aim was to evaluate the revised IAHG scoring system and its ability to identify AIH overlap in PBC. METHODS: One hundred forty-one PBC patients with first-time visits to the Mayo Clinic from January 1, 1990 to December 31, 1992 were evaluated. The calculation of individual revised IAHG scores was performed and compared to original IAHG scores. RESULTS: Among 137 PBC patients with available liver histologies, use of the original IAHG scoring system detected "definite" and "probable" AIH overlap among 2.2% and 62% of cases, respectively. Application of the revised IAHG scoring system, however, revealed no individuals (0%) with definite AIH overlap (>15 points). Twenty-six subjects (19%) fulfilled IAHG criteria for probable AIH overlap (10-15 points). The presence of antinuclear antibody and/or smooth muscle antibody positivity (p = 0.05), other autoimmune disorders (p < 0.01), and total histological score (p < 0.001) were significantly greater in the PBC plus probable AIH group than in subjects with PBC alone. CONCLUSION: A reduction in the prevalence of definite 2.2% vs 0%) and probable (62% vs. 19%) AIH overlap among PBC subjects was observed with use of the revised IAHG coring system relative to the original criteria. Applicability of the revised IAHG scoring system, however, remains questionable, as nearly 20% of PBC patients will be classified with probable AIH overlap.

Autoimmune Diseases↗
PubMed2002

Results of long-term ursodiol treatment for patients with primary biliary cirrhosis.

OBJECTIVE: When ursodeoxycholic acid (UDCA) is used for the treatment of primary biliary cirrhosis, it has been associated with biochemical improvement, histological stability, reduced risk of esophageal varices, and increased survival free of transplantation. There is limited information available about the long-term outcome of these patients with primary biliary cirrhosis on UDCA treatment. To address this, we reviewed the long-term results from patients enrolled in our original randomized study with up to 12 yr of follow-up. METHODS: From April 1988 to March 1992, a total of 180 patients were enrolled into a randomized, controlled trial evaluating UDCA (n = 89) versus placebo (n = 91). When the randomized portion of the study concluded in May 1992, patients were switched to active medication and followed for up to an additional 8 yr. RESULTS: Twenty-eight patients originally assigned to UDCA and 42 patients originally assigned to placebo have died or undergone transplantation. The patients who died or were transplanted were more histologically advanced at entry (p < 0.001). Seventy-six of the remaining 110 patients return for regular follow-up; mailed questionnaires were returned by an additional 25 patients, and nine patients have been lost to follow-up. Twenty-two of the 76 patients we follow have normal liver tests (ALP, bilirubin, and AST). Patients with normal liver tests had significantly lower levels of ALP and AST at baseline (p < 0.05), but did not differ in histological stage or total bilirubin from those with persistently abnormal tests. CONCLUSIONS: UDCA appears to be of most benefit when instituted in early stage disease. Although a substantial percentage of patients will achieve biochemical normalization on UDCA alone, there is a continued need for therapeutic options for others who have less complete biochemical responses.

Adult↗
PubMedDate not supplied

Current concepts in the pathogenesis of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile duct with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. The serologic hallmark of PBC is the presence of autoantibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Like other better characterized autoimmune diseases, there appears to be a genetic susceptibility and a triggering event that initiates the autoimmune attack on bile duct cells. DRB1*0801 and DRB1*0803 are the major susceptibility alleles among Northern European and Japanese populations, respectively. The generation of immune responsiveness to self-antigen can result in pathogenic autoimmune damage of the intrahepatic biliary epithelial cells mediated by both humoral and cellular immune responses. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators. Human and animal studies have suggested that the induction of an antibody response reactive with self-antigen may result from a number of different priming events. Among the events demonstrated to induce an antibody response cross-reactive with self-PDC are exposures to bacterial PDC or retroviral proteins or xenobiotics or microchimerism. The diversity of the potential events giving rise to antibody responses cross-reactive with PDC, which could promote subsequent T-cell tolerance breakdown, suggests the intriguing possibility that PBC could represent a condition with a common final pathway but with multiple triggers able to induce a B-cell response cross-reactive with self-PDC. There are important questions about the pathogenesis of PBC which remain unanswered.

Autoimmune Diseases↗