Pharmacotherapeutic options in inflammatory bowel disease: an update.

Chronic inflammatory bowel disease (IBD) refers to two diseases: Crohn's disease (CD) and ulcerative colitis (UC). The etiology of IBD remains unknown. The understanding of the pathogenesis has expanded greatly over the last decade. The combination of genetic risk factors, abnormalities in the immune system, vascular and neural factors, and random environmental factors may all play an important role. Most treatments currently in use have multiple action. The choice of appropriate medical treatment is determined by the status (inductive or maintenance therapy) and severity of the disease and the potential for toxicity. Despite the variety of medical therapies available for the treatment of IBD, none is ideal. Ongoing research into the well-established drugs, as well as novel agents with more precise targets, may contribute to an optimal therapy of IBD in the near future. In this paper the current (5-aminosalicylates, glucocorticosteroids, thioguanine derivatives, methotrexate, cyclosporin and infliximab) as well as some of the new (mycophenolate mofetil and thalidomide) therapeutic options are reviewed.

The accuracy of the Helicobacter pylori stool antigen test in diagnosing H. pylori in treated and untreated patients.

OBJECTIVE AND DESIGN: To evaluate the performance of the Helicobacter pylori stool antigen test (HpSA test) in detecting H. pylori infection and monitoring the effect of treatment. This was done in two separate studies using either a biopsy or the 13C-urea breath test based 'gold standard' (in untreated and treated patients, respectively). SETTING: Endoscopy units of two general hospitals. PATIENTS: One hundred and twenty-eight dyspeptic patients undergoing endoscopy in the first study. Sixty-five patients receiving anti-H. pylori treatment in the second study. RESULTS: Sensitivity and specificity in untreated patients were 96.3% and 81.8%, respectively. Seven days after treatment, these figures were 20% and 95%, and 4 weeks after treatment they were 40% and 95%. CONCLUSION: The HpSA test is accurate in untreated patients but fails in monitoring treatment success.

Bilateral excision of perinephric fat and fascia (Gerota's fasciectomy) in the treatment of intractable chyluria.

A case is described of a 59-year-old black man with massive chyluria, probably due to previous infection with Wuchereria bancrofti. Notably, no edema was present despite a urinary protein loss of 40 gm. per day resulting in a serum albumin level of 13 gm./l. Conservative treatment after lymphography, including prolonged bedrest and a medium chain triglyceride diet, was unsuccessful. Bilateral excision of the perinephric fascia and fat (Gerota's fasciectomy) in 2 separate operative sessions finally resulted in complete resolution of the chyluria.

Adrenocortical insufficiency: a rare presentation of non-Hodgkin's lymphoma.

A 77-year-old man presented with adrenocortical insufficiency, for which a cause could not be identified during life. Six weeks after the diagnosis, the patient died, while receiving adequate cortisol therapy, from a fulminant gastrointestinal bleeding. A pleural effusion, found shortly before death, later showed malignant lymphoid cells. At autopsy, a widely spread, diffuse, malignant B-cell lymphoma with destruction of, amongst others, both adrenals was found. The retroperitoneal, but not the peripheral lymph nodes were involved, thereby explaining failure of diagnosis while the patient was living. This is the first description of a diffuse B-cell Non-Hodgkin's lymphoma presenting with adrenocortical insufficiency. Potentially curable malignant invasion of the adrenals can present with adrenocortical insufficiency, and may thus justify imaging of the adrenals with sensitive techniques in elderly patients with unexplained primary adrenocortical insufficiency.

High antigen reactivity in mononuclear cells from sites of chronic inflammation.

Antigen-specific in-vitro responses of mononuclear cells from synovial fluid and peripheral blood of patients with rheumatoid arthritis were compared with those of mononuclear cells from pleural exudate and peripheral blood of non-rheumatoid-arthritis patients with chronic pleuritis not caused by tuberculosis. The antigens tested were an acetone-precipitable fraction of Mycobacterium tuberculosis (AP-Mt), an Escherichia coli lysate containing the 65 kD heat-shock protein of M bovis BCG (65 kD/E coli), the M bovis heat-shock protein alone (65 kD), and E coli alone. The mean proliferative responses to AP-Mt were higher in synovial-fluid than in peripheral-blood mononuclear cells in rheumatoid arthritis patients (mean [SEM] stimulation index 10.5 [3.1] vs 2.6 [0.9]) and in pleural-exudate than in peripheral-blood mononuclear cells in the pleuritic patients (7.5 [1.7] vs 3.5 [2.0]). The same pattern was seen for the other three antigens. Only 1 of 26 synovial-fluid mononuclear cell samples from rheumatoid arthritis patients showed a positive response (stimulation index 3 or more) to 65 kD compared with 5 of 22 pleural-exudate mononuclear cell samples, so 65 kD seems not to be the major antigen recognised by synovial-fluid T cells in rheumatoid arthritis. Enhanced reactivity against mycobacterial and other bacterial antigens is not restricted to mononuclear cells from chronically inflamed joints but seems to be a common feature of chronic inflammation.

Anti-CD27 monoclonal antibodies identify two functionally distinct subpopulations within the CD4+ T cell subset.

Anti-CD27 monoclonal antibodies react with a cell surface molecule expressed on medullary thymocytes and a large subpopulation (75%) of peripheral blood T lymphocytes. This study was undertaken to analyze the functional capacities of CD27+ and CD27- subpopulations within the CD4+ subset. In addition, we investigated whether CD27 subpopulations belong to two mutually exclusive T cell sublineages. Proliferation upon lectin stimulation by either phytohemagglutinin or pokeweed mitogen (PWM) was found to be consistently higher in CD4+CD27+ cells compared to CD4+CD27- cells. In contrast, CD27+ and CD27- cells did not differ in anti-CD3, soluble antigen or interleukin (IL)2-induced proliferation. In PWM-driven B cell differentiation, CD4+CD27+ cells provided helper activity on IgM production, while CD4+CD27- cells did not. The differences observed between CD4+CD27+ and CD4+CD27- cells in both proliferation and T helper activity on IgM production can, at least in part, be explained by the inadequate production of IL2 by CD27- cells upon lectin stimulation. In contrast, CD27+ and CD27- subpopulations did not differ in the production of interferon-gamma. CD27- cells could be induced to express the CD27 antigen through stimulation of these cells with immobilized anti-CD3 antibodies. After 3 days of culture, approximately 50% of the cells had CD27 membrane expression, whereas after 6 days 80% of the cells express the antigen. We conclude that anti-CD27 antibodies identify two functionally distinct T cell populations within the CD4+ subset. These subpopulations apparently do not belong to two separate T cell sublineages, but may reflect differences in the activation state of CD27+ vs. CD27- peripheral blood T lymphocytes.