The long-term effect of ursodeoxycholic acid on laboratory liver parameters in biochemically non-advanced primary biliary cirrhosis.

BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) has an established effect on liver bio-chemistries in primary biliary cirrhosis (PBC). Few studies have evaluated long-term laboratory treatment effects and data beyond 6 years are not available. The aim of this study was to assess the long-term evolution of liver bio-chemistries during prolonged treatment with UDCA in biochemically non-advanced PBC. PATIENTS AND METHODS: Prospective multicenter cohort study of patients with PBC with pretreatment normal bilirubin and albumin, treated with UDCA 13-15 mg/kg/day. At yearly intervals, follow-up data including serum bilirubin, alkaline phosphatase (ALP), transaminases, albumin and IgM were collected. Data were analyzed with a repeated measurement model. RESULTS: Two hundred and twenty-five patients were included and followed during a median period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total biochemical improvement was achieved, the maximum response was observed after 3 years. After initial improvements, bilirubin and AST levels increased and albumin levels significantly decreased after 6-10 years. However, these changes were of limited magnitude. The beneficial effects on ALT and ALP were maintained while IgM continued to decrease. CONCLUSION: In non-advanced PBC the biochemical response to UDCA is maintained up to 15 years. The long-term evolution of bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level normalised and levels continued to decrease during the period of follow-up.

Flexible endoscopic treatment of Zenker's diverticulum: a new approach.

BACKGROUND AND STUDY AIMS: In the past, a number of treatment modalities have been used for the management of a Zenker's diverticulum. These include transcervical diverticulectomy, myotomy, or laser or diathermy treatment via rigid endoscopes. Up to the present, no reports of the treatment of a Zenker's diverticulum with a flexible endoscope have been published. PATIENTS AND METHODS: In this study, we present the results of our first 20 patients (13 male; mean age 82 years) prospectively treated with a flexible endoscope applied through diathermy. All patients had significant symptoms such as dysphagia, recurrent aspiration pneumonia and/or weight loss. RESULTS: Treatment using a mean of three sessions per patient was successful, with a good symptomatic response in all subjects. There were no severe complications associated with the therapy. Four patients complained about a sore throat for a few days. During follow-up (mean 6-7 months), three patients died due to unrelated causes, and 17 remained asymptomatic. CONCLUSIONS: An important advantage is that it is possible to perform the treatment without general anesthesia, and therefore also in patients whose general health is poor. The technique can easily be performed in an interventional endoscopy unit. Our first experiences show that flexible endoscopic treatment is an effective and relatively safe method.

Intestinal T lymphocytes.

The intestine is largely colonized by bacteria and further exposed to an immense array of ingested and shed immunogenic material. Therefore, the gut associated lymphoid tissue plays a major role in the human immune system. It may even constitute a unique immune system of its own, since it has been demonstrated to differ anatomically, phenotypically, functionally and on a molecular basis from its systemic counterpart and other peripheral lymphoid tissue. This is ultimately reflected by the observation in (transgenic) mice that intraepithelial T cells can develop independently of the thymus. Along the same lines, a rapidly growing body of evidences suggests that human bone marrow precursors can home to the gut epithelium, rearrange their T cell receptor genes and further differentiate in the mucosal micro environment. This, and other features that characterize the 'diffuse' mucosal T cell infiltrate will be discussed.

Phenotypic and molecular characterization of human monoclonal TCR gamma/delta T-cell lines from jejunum and colon of healthy individuals.

We have performed a phenotypic and molecular analysis of monoclonal TCR gamma/delta T-cell lines derived from jejunal and colonic biopsies of healthy individuals. Flow cytometric analysis employing a panel of 24 monoclonal antibodies (MoAbs) demonstrated that intestinal TCR gamma/delta intraepithelial lymphocytes (IEL) constitute a phenotypically heterogeneous population. Nucleotide sequence analysis of expressed TCR delta variable (V) regions revealed the dominant utilization of the V delta 2 and D delta 3 gene segments and frequent rearrangement of J delta 3. IEL V delta regions displayed extensive junctional diversity as a result of N and P insertion and the utilization of D delta 3 in all three reading frames. The results demonstrate that intestinal TCR gamma/delta T cells from healthy individuals constitute a phenotypically heterogeneous population expressing V delta regions that differ from their systemic counterparts.