Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis.

Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P < 0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P < 0.001) and mucosal inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P < 0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.

Quantification of circulating varicella zoster virus-DNA for the early diagnosis of visceral varicella.

Varicella zoster virus (VZV)-DNA was quantified in peripheral blood of 2 patients with visceral varicella due to endogenous reactivation. An 18-year-old male contracted varicella following the courses of chemotherapy for T cell lymphoma. Another 18-year-old male suffered from varicella 16 months after the complete engraftment of hematopoietic stem cell transplantation. Both patients had past VZV infection, but no recent contact with the disease. Paralytic ileus and ascites preceded the skin lesions. Quantitative real-time polymerase chain reaction revealed >200 copies of VZV per 1 ml of whole blood before or at the time when cropping vesicles emerged. The viral load reflected their prolonged clinical courses. Similar levels of VZV-DNA were detected in primary varicella patients, but not in herpes zoster patients or immunocompromised children without varicella or zoster. Quantitative monitoring of circulating VZV-DNA may be useful for the diagnosis and assessing the treatment response of visceral varicella in immunocompromized hosts.

High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients.

Human herpesvirus 6 (HHV-6) infection in recipients of cord blood stem cell transplants (CBSCTs) was estimated by semiquantitative and real-time quantitative polymerase chain reaction (PCR) and reverse-transcription PCR. Of the CBSCT recipients, 7 (70%) of 10 had active HHV-6 infection after transplantation, and all 7 were inferred from their age to have already had a primary infection. Because HHV-6 DNA is seldom detected in cord blood, these cases were considered likely to represent reactivation. In contrast, the 3 patients without HHV-6 infection were all believed to be naive regarding HHV-6 primary infection because of their age and the results of PCR assays given before the transplantation procedure. The incidence of HHV-6 infection after transplantation was significantly higher (P <.05) than after bone marrow (BM) transplantation and peripheral blood stem cell (PBSC) transplantation, when recipients without primary HHV-6 infection prior to transplantation were excluded (CBSCT, 100%; BMT/PBSCT, 56.3%). Real-time PCR revealed a higher level of viral DNA in the peripheral blood mononuclear cells from CBSCT recipients than from BMT/PBSCT recipients or patients with exanthem subitum (P <.05). HHV-6 mRNA of the U79/80 gene was also detected by reverse-transcription PCR in all analyzed patients with HHV-6 infection. Its detection was correlated with the emergence of viral DNA in the plasma and symptoms such as fever and rash. Thus, HHV-6 infection was more frequent and the viral load was higher in CBSCT recipients with prior primary infection.

Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia').

So-called 'vascular neoplasia' (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60-year-old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node-like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit-like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL-6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL-6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon.