Intestinal Behçet's disease associated with non-Hodgkin's lymphoma

A 45-year-old man with intestinal Behçet's disease noticed an enlarged right cervical lymph node, and was diagnosed with diffuse large cell type, non-Hodgkin's lymphoma. The intrapelvic lymph tract was markedly deformed because of recurrent ileocecal ulceration, and conventional lymphoscintigraphy with a common tracer did not abolish the suspicion that lymphoma cells may have invaded the lymph nodes. Dynamic lymphoscintigraphy with a new tracer,^99mtechnetium-diethylene triamine pentaacetic acid-human serum albumin, because of its high detection sensitivity, was very useful for excluding this suspicion, and for determining the clinical stage of lymphoma. Combination induction chemotherapy led to complete remission without any adverse effects, but subsequent supportive therapy with same protocol could not be completed because of progression of the intestinal lesions. Special management for the intestinal lesions, such as bowel rest, may be essential with chemotherapy for patients with intestinal Behçet's disease.     

The usefulness of<Superscript>99m</Superscript>Tc-hexamethylpropyleneamineoxime white blood cell scintigraphy in a patient with eosinophilic gastroenteritis

White blood cell (WBC) 99mTc-hexamethylpropyleneamineoxime (HMPAO) scintigraphy was performed in a patient with eosinophilic gastroenteritis. WBC accumulation was detected in the terminal ileum to descending colon, and pathological studies demonstrated eosinophilic infiltration at the same region. 99mTc-HMPAO-WBC scintigraphy was proved to be a useful tool for the detection of eosinophilic infiltration in eosinophilic gastroenteritis.     

Clinical significance of the venous occlusion test on systemic lupus erythematosus patients with a focus on changes in blood levels of tissue plasminogen activator, von Willebrand factor antigen, and thrombomodulin.

We investigated the clinical significance of the venous occlusion (VO) test on patients with systemic lupus erythematosus (SLE) with or without circulating lupus anticoagulant (LA) concerning whether changes in the blood coagulation and fibrinolysis system in vivo subsequent to VO reflect mechanical stimulation of the endothelium or presence/development of endothelial damage. The tissue plasminogen activator antigen (tPA:Ag) before VO was much lower in the LA-positive patients than in the LA-negative ones (p < 0.01) and the von Willebrand factor antigen (VWF:Ag) pre-VO was significantly higher in the patient group, regardless of LA status, than in the control group (p < 0.01). But the mean increment in tPA:Ag and VWF:Ag post-VO, when expressed as the percentage of the baseline level, showed no appreciable difference between LA-positive and -negative groups. Thrombomodulin (TM) basically, on the other hand, was higher in the patients of either LA status than in the controls (p < 0.01) with a significant post-VO increase in the SLE group, which was more marked in the LA-positive patients, against no substantial change in the controls (p < 0.01). It is known that tPA and VWF:Ag are released simply as a result of endothelial stimulation and that the release of TM is preceded by endothelial damage. Based on the present results, we may well conclude that (1) the endothelium is functionally intact in SLE patients, (2) an injury of the endothelium, possibly as a consequence of vasculitis, preexists in LA-positive patients, and thus to measure the TM response to VO would offer a helpful tool in diagnosing the preexisting endothelial damage in these clinical settings.     

Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy

Invasive fungal infections are fatal complications for patients on chemotherapy, and antifungal prophylactic treatment has been commonly recommended. Because its clinical and economic impact is not well known, we evaluated cost-effectiveness of anti-fungal treatment for patients who were neutropoenic as a result of chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$), and incremental cost-effectiveness ratio (US$/YLS). The following treatment strategies for fungal infections were compared: (1) prophylactic fluconazole strategy: oral fluconazole administration concurrently with chemotherapy; (2) empirical amphotericin B strategy: empirical intravenous amphotericin B administration at the point where fever is detected; and (3) no prophylaxis strategy: intravenous micafangin administration at the point where fungal infections is diagnosed. Baseline analyses showed that prophylactic fluconazole strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS). The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was 625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to empirical amphotericin B strategy. Baseline result was found to be robust through sensitivity analyses. Our study showed that concurrent administration of oral fluconazole during induction chemotherapy appears to ensure clinical benefits together with acceptable cost-effectiveness.     

Genetic contribution of the tumour necrosis factor (TNF) B + 252*2/2 genotype, but not the TNFa,b microsatellite alleles, to systemic lupus erythematosus in Japanese patients

The contribution of the tumour necrosis factor (TNF) B + 252 (TNFB) dimorphism and microsatellite polymorphisms of TNFa and TNFb to the pathogenesis of systemic lupus erythematosus (SLE) was studied in Japanese patients. The TNFB dimorphism was determined using the restriction fragment length polymorphism (RFLP) method with NcoI digestion followed by specific polymerase chain reaction (PCR) amplification. TNFa and TNFb microsatellite polymorphisms were determined using the DNA sequencer and GeneScan program (Applera Corporation, Foster City, CA) followed by specific PCR amplification. HLA-DRB1*15 typing was carried out by the PCR-sequence specific conformational polymorphism (SSCP) method. In SLE, the allele frequency of TNFB*2 significantly increased (68.9%, P < 0.05) and the genotype frequency of TNFB*2/2 also increased (52.8%, P < 0.05). TNFB*2 showed no significant linkage disequilibrium with HLA-DRB1*1501. The prevalence of TNFa13 and TNFb4 showed very slight increases, but these increases were not significant. An association analysis indicated that TNFB*2/2 conferred greater, or at least equal, susceptibility to SLE in Japanese patients in comparison with HLA-DRB1*1501. The TNFB*2/2 genotype may contribute additively with DRB1*1501 to SLE in Japanese patients. No association was observed between auto-antibodies and TNF. TNFB*2 is a genetic marker for SLE in Japanese patients, while TNFa and TNFb microsatellites are not associated with SLE.     

Chronic myelogenous leukemia cells convert to myofibroblasts in vitro: effect of vascular endothelial growth factor on development of the microenvironment

To elucidate the biological characteristics of chronic myelogenous leukemia (CML) cells, we observed morphological and functional changes of CML cells during primary long-term culture, in which their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental CML cells including BCR-ABL fusion gene, and produced cytokines such as granulocyte colony-stimulating factor, interleukin-6, and vascular endothelial growth factor (VEGF)-A. When cultured on the CML-derived myofibroblasts, parental non-adherent CML cells significantly proliferated. When anti-VEGF-A-neutralizing antibody was added to the cultures, non-adherent CML cell proliferation was significantly inhibited. These observations indicate that CML cells can convert their morphology and function to adherent myofibroblasts, and produce a significant amount of cytokine to give a growth-promotion activity to CML cells.