Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell chronic lymphocytic leukemia.

R-etodolac is a novel pro-apoptotic agent with potential antitumor activity against B-cell chronic lymphocytic leukemia (B-CLL). This phase I clinical trial was conducted to determine the tolerability, safety, and maximum tolerated dose (MTD) of R-etodolac, administered orally twice a day (BID), in patients with B-CLL. Secondary objectives included evaluating clinical response, pharmacodynamic activity (reduction of lymphocytes), and pharmacokinetic (PK) profile. Forty-three patients were enrolled in the study. The most frequently reported adverse events were diarrhea, rash, pruritus, and headache. Increases in alanine aminotransferase (ALT) were also observed. Adverse events were generally mild and self-limiting, although in an apparent dose-response relationship, grade 2 and 3 gastrointestinal toxicities and grade 3 skin toxicities were reported with the highest dose regimens (1,800 and 2,400 mg BID). Hematologic toxicity was rare. The MTD was determined to be 1,200 mg BID. PK results indicated that oral absorption of R-etodolac was rapid (time to maximum concentration ranged from 2 to 4 h), and the half-life ranged from 5 to 7 h. The increase in maximum concentration, however, was not proportional to the increase in dose. R-etodolac significantly reduced absolute lymphocyte count (ALC) in B-CLL patients in a dose-dependent manner up to 1,800 mg BID and caused partial responses in 2 patients. Further study of R-etodolac as a possible new maintenance therapy or as a part of combination therapy of B-CLL appears warranted.

A case of persistent anemia and alcohol abuse.

BACKGROUND: A 56-year-old male with a history of excess alcohol consumption for over 10 years and type 2 diabetes mellitus (diagnosed 14 years previously) presented to the accident and emergency department with severe anemia and a 1-day history of nausea and 'coffee ground' vomiting. He had been admitted to hospital on several occasions in the previous 18 months, primarily because of anemia, and had received 30 units of transfused blood during this period. Previous extensive investigations included six esophagogastroduodenoscopies and a colonoscopy, a barium follow-through study, and a radionucleotide Meckel's scan. The prior working diagnosis was anemia secondary to blood loss. INVESTIGATIONS: Laboratory investigations (full blood count [including reticulocytes], microscopic blood film examination, hematinics, liver function tests with direct and indirect bilirubin measurement, prothrombin time, and lactate dehydrogenase level), transjugular liver biopsy and bone-marrow biopsy. DIAGNOSIS: Alcohol-related anemia caused by acute hemolysis, sideroblastic anemia and cirrhosis. MANAGEMENT: Correction of anemia by blood transfusion (6 units), and prevention of recurrence by strict abstinence from alcohol.

A simple PCR/RFLP analysis can differentiate between Candida albicans, Aspergillus niger, and Aspergillus fumigatus.

The clinical management of immunocompromised patients depends on the rapid identification of infectious agents such as fungal pathogens. The procedure described here for accomplishing this uses a sensitive polymerase chain reaction method, previously reported, combined with restriction-enzyme digestion to distinguish between Candida and Aspergillus species and to classify Aspergillus strains.

Recombinant human interleukin 11 and bacterial infection in patients with [correction of] haematological malignant disease undergoing chemotherapy: a double-blind placebo-controlled randomised trial.

BACKGROUND: Bacteraemia in patients with haematological malignant disease causes substantial morbidity. Recombinant human interleukin 11 (rhIL-11) prevents gastrointestinal epithelial disintegrity and has immunomodulatory actions. Our aim was to ascertain whether or not treatment with rhIL-11 can prevent gut-associated infections. METHODS: We did a double-blind placebo-controlled randomised trial, to which we enrolled 40 patients with haematological malignant disease who were undergoing chemotherapy. Patients received either rhIL-11 50 microg/kg (n=20) or placebo (n=20) daily by subcutaneous injection from the day before the start of chemotherapy until resolution of neutropenia or for 21 days, whichever was longer. Our primary outcome measure was a reduction in bacteraemia. Analysis was by intention to treat. FINDINGS: Significantly fewer patients who received rhIL-11 rather than placebo developed bacteraemia, particularly of gastrointestinal origin: the proportion of patients with at least one positive blood culture was 0.65 and 0.25, respectively (p=0.02). The numbers of patients (placebo vs rhIL-11) for each number of distinct isolates were: no organism isolated seven versus 15, one organism nine versus four, two organisms two versus one, three organisms one versus none, and four organisms one versus none (p=0.01), suggesting a lower bacterial load in the rhIL-11 than in the placebo group. Time to first bacteraemic event was longer in patients who received rhIL-11 (p=0.03) than in those who received placebo. INTERPRETATION: rhIL-11 reduces the frequency and load of bacteraemia in patients with haematological malignant disease undergoing chemotherapy, possibly by gastrointestinal cytoprotective or immunological mechanisms [corrected].