Factors influencing response to treatment of pulmonary tuberculosis.

We analyzed 150 patients with pulmonary tuberculosis from 1990 to 1996 (i) to evaluate the frequency of drug resistance, (ii) to elucidate factors influencing the response to chemotherapy, and (iii) to attempt to improve the therapeutic approach. Multidrug-resistant tuberculosis strains were not found. By univariate analysis, there were 8 factors associated with an increased sputum conversion time: male gender, prior treatment, complications, progressive chest radiographic findings, a high Ziehl-Neelsen stain score, lymphocytopenia, a high erythrocyte sedimentation rate (ESR), and hypoproteinemia. Complications, prior treatment, a high Ziehl-Neelsen stain score, and a high ESR were independent predictive factors in a Cox proportional hazard model. Recursive partitioning and amalgamation (RPA) defined 3 subgroups that responded to treatment. In order to reduce the time to sputum conversion, poor responders according to the RPA should be treated with a 4-drug regimen containing pyrazinamide.</p

Direct ATM activation by toxic metabolites

Division of Molecular Patholog

Epithelioid Hemangioendothelioma of the Liver Showing Spontaneous Complete Regression after the Cessation of Methotrexate Intake

A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0–40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression

The Usefulness of CYFRA21-1 in Diagnosing and Monitoring Malignant Pleural Mesothelioma

Five patients with malignant pleural mesothelioma (MPM) were studied to determine whether CYFRA 21-1 is useful for diagnosis of this disease. In pleural effusions, the median concentration of CYFRA 21-1 from 4 patients with MPM was significantly higher than for 34 patients with benign diseases. The sensitivity of serum CYFRA 21-1 for diagnosis of MPM was 40% and its concentration changed in proportion to disease activity in all cases. Immunohistochemically, anticytokeratin 19 antibody revealed strong staining in both epithelial and sarcomatous MPM tissues. Based on these results, we conclude that measurement of CYFRA 21-1 in pleural effusions and serum may be useful for diagnosing and monitoring MPM.</p

Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome : a case report

Background: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. Case presentation: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient’s attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. Conclusions: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated