Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation.

Human herpesvirus 6 (HHV-6) causes life-threatening encephalopathy in recipients of allogeneic SCT, but no consensus has been reached regarding appropriate preventive methods. This study evaluated a plasma HHV-6 viral load-guided preemptive approach against HHV-6-associated encephalopathy. Plasma real-time PCR assay was performed once a week. Among 29 patients, 19 developed positive plasma HHV-6 DNA. Median maximum plasma HHV-6 DNA was 4593.5 copies/ml plasma (range, 150.0-127 891.0 copies/ml plasma). In one of eight events with low-level HHV-6 DNA (defined as <1000 copies/ml plasma) and four of seven events with mid-level HHV-6 DNA (1000-9999.5 copies/ml plasma), HHV-6 loads in plasma subsequently continued increasing. Ganciclovir was administered against six of nine patients with high-level HHV-6 DNA (> or =10,000 copies/ml plasma). High-level HHV-6 DNA resolved similarly in both groups with or without ganciclovir therapy. Among the nine patients with high-level HHV-6 DNA two developed encephalopathy. As encephalopathy developed before the detection of high-level HHV-6 DNA in plasma, these two patients had not received preemptive ganciclovir therapy. In conclusion, our preemptive approach against HHV-6-associated encephalopathy cannot prevent all cases of HHV-6 encephalopathy in SCT recipients due to the dynamic kinetics of plasma HHV-6 viral load.

A rare case of eosinophilic pleuritis due to sparganosis.

A rare form of sparganosis with eosinophilic pleural effusion is reported. A 62-year-old man was admitted to our hospital with left pleural effusion, and diagnosed immunologically as having sparganosis. Eosinophilia was seen in both peripheral blood and pleural effusion. The level of interleukin (IL)-5 was elevated in the pleural effusion, but not in peripheral blood. The patient was treated successfully with three consecutive doses of praziquantel (75 mg/ kg/day). After the treatment, the antibody titer in serum decreased and the eosinophil number in the peripheral blood returned to the normal level. Thus, sparganosis should be included in the differential diagnosis for eosinophilic pleuritis. The immunoserological screening test using multiple-dot ELISA is helpful to identify the causative pathogen.

Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia.

BACKGROUND AND METHODS: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. RESULTS: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. CONCLUSION: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.

Superoxide dismutase in alveolar macrophages from patients with diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is characterized by chronic neutrophil-mediated inflammation of the airway mediated by oxygen radical production. DPB can be controlled with low-dose and long-term erythromycin therapy based on its anti-inflammatory effect. OBJECTIVE: In this study, the antioxidant levels were analyzed as an anti-inflammatory effect of erythromycin in the patients. METHODS: We investigated the activity and protein level of an antioxidant enzyme, Cu, Zn-superoxide dismutase (SOD) in alveolar macrophages (AMs) of patients with DPB before and after erythromycin therapy. AMs were obtained from bronchoalveolar lavage fluid. RESULTS: There was no significant difference in the activity of Cu, Zn-SOD between normal subjects and untreated patients. Erythromycin therapy (600 mg/day) significantly increased the activity of the enzyme relative to that before therapy and normal subjects [18.2 units/10(6) cells (9.2-26.2) vs. 4.4 units/10(6) cells (1.1-9.3), p < 0.01 and 10.4 units/10(6) cells (2.4-20.6), p < 0.05, respectively]. Furthermore, the protein level of Cu, Zn-SOD in AMs in treated patients was significantly higher than in the other two groups [69.4 ng/10(6) cells (34.2-147.1) vs. 20.1 ng/ 10(6) cells (16.9-39.8) for untreated patients, p < 0.01 and 43.2 ng/10(6) cells (32.6-68.2) for normal subjects, p < 0.01], but the levels in the latter groups were not different. CONCLUSION: Our results suggest that one of the anti-inflammatory effects of erythromycin in DPB may be, in part, mediated by enhancement of antioxidant activity in AMs.

Elevated chemokine levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia.

BACKGROUND: Allergic lung inflammation is caused by accumulation and activation of different leukocyte subsets, such as eosinophils and T lymphocytes, in the lung. The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and may play an important role in allergic lung inflammation. OBJECTIVE: The purpose of this study was to evaluate the role of various chemokines, including eotaxin, RANTES, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1beta, and IL-8 in the pathogenesis of eosinophilic pneumonia (EP). METHODS: The concentrations of eotaxin, RANTES, MCP-1, MIP-1beta, and IL-8 in bronchoalveolar lavage fluid (BALF) were measured by using ELISA in 15 patients with EP, 10 with idiopathic pulmonary fibrosis, 10 with sarcoidosis, and 11 healthy volunteers. RESULTS: Eotaxin in BALF was high only in patients with EP, and its level correlated significantly with the number of eosinophils in BALF of patients with EP and healthy volunteers. MCP-1 and MIP-1beta in BALF were preferentially increased in patients with EP. There was a significant correlation between MCP-1 levels and the number of macrophages in BALF of patients with EP and healthy volunteers. CONCLUSION: Our findings suggest that these CC chemokines contribute to the pathogenesis of EP through the specific recruitment of leukocyte subsets in the lung.

Elevated levels of beta-chemokines in bronchoalveolar lavage fluid (BALF) of individuals infected with human T lymphotropic virus type-1 (HTLV-1).

Pulmonary complications are known to develop in HTLV-1 carriers, including T lymphocytic alveolitis, and increased IL-2 receptor alpha (CD25)-bearing T cells have been found in BALF. Several chemokines may contribute to accumulation of T lymphocytes in the lungs of HTLV-1 carriers. Here, we compared the distribution of T lymphocyte subsets and beta-chemokines, such as macrophage inflammatory peptide-1alpha (MIP-1alpha), regulated on activation normal T expressed and secreted (RANTES), and macrophage chemoattractant protein-1 (MCP-1), in BALF and peripheral blood between HTLV-1 carriers and non-infected healthy normal subjects. Flow cytometric analysis with MoAbs to cell surface antigens was used to identify T lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and non-infected healthy controls (n = 10). The levels of different beta-chemokines were estimated by ELISA. High percentages of CD3+ cells, CD3 expressing HLA-DR antigen and CD3+CD25+ cells were detected in BALF of HTLV-1 carriers compared with non-infected controls. The concentration of MIP-1alpha in BALF of patients was significantly higher than in non-infected healthy controls and correlated well with the percentage of CD3+CD25+ cells. The level of RANTES in BALF was also significantly high in HTLV-1 carriers, but did not correlate with the percentage of CD3+CD25+ cells. On the other hand, the level of MCP-1 in BALF of HTLV-1 carriers was not different from that of controls. Our results suggest a possible interaction between activated T cells bearing CD25 and beta-chemokines, especially MIP-1alpha, which may contribute to the pulmonary involvement in HTLV-1 carriers.