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Background: Inflammatory diarrhoea (ID) resulting from Shigella, Salmonella, Campylobacter and Entamoeba histoly-tica requires specific diagnosis for therapy. Differentiation between ID and non-inflammatory diarrhoea (NID) is often not clinically possible. A faecal occult blood test (FOBT) correlates with faecal leucocytes. Lactoferrin indicates an inflammatory process as a marker for faecal leucocytes. We evaluated diagnostic values of lactoferrin latex aggluti- nation test (LT) either alone or in combination with FOBT, correlating with stool microscopy and microbiology in differentiating ID from NID. Methods: The study population constituted patients enrolled in 2% systematic sampling of patients under Diarrhoeal Disease Surveillance System of Dhaka Hospital, ICDDR,B. Results: Between July and November 2002, 594 patients were enrolled; evaluation of FOBT and LT were done in 448/594 (75%) patients from whom either a single enteropathogen (315/594, 53%) or no pathogen (133/594, 22%) were identified and 146 were excluded for multiple pathogens. Invasive and non-invasive pathogens were isolated from 24% and 76% of the patients. FOBT and LT were positive in 40% and 39% of the samples. The sensitivities, specificities, PPVs, NPVs, and accuracies of FOBT were 55, 63, 24, 87 and 62%, and LT were 52, 64, 23, 86 and 62%, respectively. Conclusion: FOBT and LT are not useful in differentiating ID from NID in diarrhoeal patients in Dhaka, Bangladesh.

BACKGROUND High doses (>or=500 mg/m) of cyclophosphamide are known to cause venoocclusive disease (VOD). The authors recently observed a patient treated with immunosuppressive cyclophosphamide doses (100 mg/day) and roxithromycin who developed VOD. Because roxithromycin inhibits cytochrome P450 (CYP) 3A4 and P-glycoprotein, the patient may have been exposed to higher cyclophosphamide and/or cyclophosphamide metabolite concentrations. METHODS The effect of roxithromycin on the metabolism and toxicity of cyclophosphamide was studied using human hepatic microsomes and a human endothelial cell line. RESULTS Cyclophosphamide or roxithromycin at concentrations from 0.05 to 500 micromol/L were not toxic to endothelial cells as assessed by lactate dehydrogenase (LDH) leakage assay. However, the combination of roxithromycin (500 micromol/L) and cyclophosphamide was toxic for all the tested cyclophosphamide concentrations (0.05 to 500 micromol/L) without clear concentration dependence (LDH ratio 38.3 +/- 11.0 [mean +/- SEM] for the combination with cyclophosphamide 0.05 micromol/L and 50.2 +/- 10.2 for the combination with cyclophosphamide 500 micromol/L; P

Objective: To report on a patient developing hepatic veno-occlusive disease while being treated with immunosuppressive doses of cyclophosphamide (≤2 mg/kg). Case Summary: A 66-year-old woman with autoimmune hemolytic anemia developed hepatic veno-occlusive disease while being treated with immunosuppressive cyclophosphamide 100 mg/day in combination with roxithromycin (total dose 600 mg/day). After all drugs were stopped, the patient recovered within 2 weeks. The Naranjo probability scale indicated a probable relationship between veno-occlusive disease and treatment with cyclophosphamide in this patient. Discussion: Since roxithromycin inhibits CYP3A4, which is involved with cyclophosphamide metabolism, a drug-drug interaction could have been responsible. In addition, roxithromycin is an inhibitor of the drug transporter P-glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial cells. Alternatively, since cyclophosphamide has been reported to induce apoptosis, roxithromycin could have rendered endothelial cells more vulnerable for apoptosis. Conclusions: In specific patients, cyclophosphamide can be associated with hepatic veno-occlusive disease at immunosuppressive doses.

Microscopic stool examination can distinguishinflammatory from noninflammatory diarrheas. Themodified guaiac test was shown to have good correlationto stool microscopy. In a prospective study we evaluated the diagnostic accuracy of a modified guaiactest (ColoRectal-Test, Roche) and of an immunologicaltest for fecal haemoglobin (Colo-Immun-Test, Roche) inrelation to the diarrheal pathogens identified and compared it with the stool microscopy. In 304patients, clinical presentation, stool microscopy, stoolculture, and modified guaiac test were recorded.Sensitivity of the guaiac test was 69% as compared to 63-67% for the stool microscopy. Specificitycould be improved by 10-15% using an immunological testto exclude false-positive guaiac reactions. A modifiedguaiac test can replace microscopic stool examination to distinguish between inflammatoryand noninflammatory diarrhea. Immunological testing foroccult blood can improve the specificity of the guaiactest, but is too elaborate to serve as a screening test. The modified guaiac test can easily behandled by community health workers and could beimportant in the diagnostic work-up for acute infectiousdiarrhea.