Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide

Initiation of coagulation by tissue factor (TF) is a potentially powerful regulator of local inflammatory responses. We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation of Escherichia coli lipopolysaccharide (LPS 0111:B4). At the time of injury, rats received one dose of site-inactivated FVIIa (FFR-FVIIa) or saline intravenously. At 0, 6,12, 24, and 48 h after injury, lungs were examined for histologic changes and bronchoalveolar lavage (BAL) was performed to assess protein, lactate dehydrogenase (LDH) activity, cell counts, and cytokine levels. LPS-injured rats treated with FFR-FVIIa showed decreased intra-alveolar inflammation and fibrin deposition by light microscopy compared with untreated rats. This was accompanied by decreased protein leakage (P < 0.0001), LDH activity (P < 0.0001), and local elaboration of interleukin (IL)-1beta, IL-6, and IL-10 (all P < 0.0001), but not tumor necrosis factor (TNF)-alpha. Protection was associated with reduction of TF mRNA expression in whole lung, but not with changes in nuclear translocation of nuclear factor (NF)-kappaB. FFR-FVIIa given 6 h after LPS afforded equivalent lung protection. Therefore, blockade of TF-FVIIa complex protects the lung from injury by LPS in part by reducing local expression of proinflammatory cytokines and may offer promise for therapy of acute lung injury.     

Increased risk of lethal graft-versus-host disease-like syndrome after transplantation into NOD/SCID mice of human mobilized peripheral blood stem cells, as compared to bone marrow or cord blood

We tested the ability of human cells from different hematopoietic tissues to generate graft versus host disease-like syndrome (GVHD) in sublethally irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tissue sources of human hematopoietic cells were: (1) bone marrow (BM), (2) nonmobilized peripheral blood (PB), (3) mobilized peripheral blood stem-progenitor cells (PBSC), and (4) cord blood (CB). To avoid interindividual donor variation, part of this study was done using BM, PB, and PBSC donated by a single healthy adult volunteer. A total of 179 NOD/SCID mice received graded human hematopoietic cell doses [5-500 x 10(6) mononuclear cells (MNC), containing 2-325 x 10(6) CD3(+) T cells, per mouse] from individual donors. Mice were observed for the development of GVHD and sacrificed 60 days after transplantation (earlier if ill). Mice were analyzed quantitatively by flow cytometry for human hematopoietic cell types and histologically, especially for human T lymphocytes infiltrating BM. No mouse transplanted with the tested doses of human CB or BM cells developed GVHD (experimentally defined as >10% human T lymphocytes infiltrating the mouse BM). For PB and PBSC, the frequencies of death, death with GVHD, and GVHD were directly related to the dose and source of human cells. Because PB cells contaminate harvested BM, the results from infused BM and PB were next combined for further analysis (BM/PB). The relative risks (hazard ratios estimated from the proportional hazards model) for death with GVHD, for each 10 human T cell dose increase, were 1.15 for BM/PB (p < 0.0001) and 1.47 for PBSC (p < 0.0001). In this in vivo xenogeneic model, the average T cell from human PBSC generated GVHD more potently than did the average T cell from human BM/PB, and the average CB T cell had a much lower GVHD potential. These results suggest that the potential for clinical GVHD from an HLA-disparate donor graft is likely to be quantitatively dependent both on the total number of T lymphocytes in the donor graft and the tissue source of the graft. Quantitative criteria for optimal T cell content of allogeneic donor hematopoietic grafts from different sources are discussed.     

Successful Percutaneous Balloon Valvuloplasty for Combined Congenital Tricuspid and Pulmonary Stenosis

Percutaneous balloon valvuloplasty was successfully performed in a 13-month-old symptomatic infant with congenital tricuspid and pulmonic valve stenosis. Both valves were dilated in the same setting, resulting in a significant hemodynamic and clinical improvement.     

Hepatitis C virus infection in chronic liver disease and hepatocellular carcinoma in Saudi Arabia

The prevalence of antibody to hepatitis C virus (HCV) was determined in 139 patients with chronic liver disease (CLD) and 42 patients with hepatocellular carcinoma (HCC) during one year at the Riyadh Military Hospital, Saudi Arabia. The anti-HCV was detected in 36 of 96 (37.5%) HBsAg-negative patients with chronic liver disease and six of 43 (13.9%) HBsAg-positive patients with chronic liver disease. In addition, 11 (42.3%) HBsAg-negative hepatocellular carcinoma patients and two of 16 (12.5%) HBsAg-positive hepatocellular patients had antibody to HCV. The anti-HCV prevalence was 1.5% in 4818 healthy blood donors and 1% in 385 antenatal patients. The overall HCV seropositivity of 30.4% in 181 liver disease patients (CLD and HCC) in Saudi Arabia is lower than that reported from European countries.     

Sexual satisfaction in survivors of bone marrow transplantation.

Of 157 (80%) adult survivors of bone marrow transplantation, 126 responded to a mailed survey 6-149 months after transplant concerning their ability to attain sexual satisfaction. Sixty-five percent of the subjects indicated some degree of sexual satisfaction (with 29% indicating a high degree of satisfaction). Thirteen percent were neutral and 22% were dissatisfied. Gonadal physiological disturbances were present in most subjects as a result of intensive treatments. Fifty-seven percent of women were receiving estrogen replacement, and only 40% had regular menses. Twenty-four percent of men had difficulty with erections and 13% had ejaculatory dysfunction. For men, difficulties with erection (r = 0.54, p less than 0.001) or ejaculation (r = 0.52, p less than 0.001) were associated with inability to attain sexual satisfaction. For women, loss of menses (r = 0.34, p = 0.008) was associated with inability to attain sexual satisfaction. Although few women had abnormally low serum estradiol (even with hormonal supplementation), and none of the 43 men tested had abnormally low serum testosterone, sexual satisfaction correlated with serum levels of estrogen in women (r = 0.42, p = 0.04) and serum testosterone in men (r = 0.28, p = 0.04). Forty-two subjects rated their level of sexual satisfaction before and after transplant. Post-transplant satisfaction was not associated with pretransplant satisfaction (r = 0.07, p = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)     

中药对过敏性紫癜肾炎患儿血浆内皮素和免疫功能的影响

用中药加雷公藤治疗过敏性紫癜肾炎患儿23例，观察其急性期、缓解期的血浆内皮素和免疫功能，并与单纯应用雷公藤的15例比较，结果中药加雷公藤组缓解或血浆内皮素和IGG、IGA均明显低于雷公藤组；T3细胞明显高于雷公藤组；T4/T8比值明显低于雷公藤组。提示中药加用雷公藤比单独使用雷公藤治疗过敏性紫问肾炎更有利于患儿血浆内皮素水平和免疫功能的恢复。