Rolling in P-selectin-deficient mice is reduced but not eliminated in the dorsal skin

P-selectin-mediated rolling is believed to be important in the recruitment of leukocytes to tissue after ischemia-reperfusion injury. The dorsal skin chamber was used to examine differences in the rolling and stable adhesion of circulating leukocytes in subcutaneous (SC) vessels of P-selectin-deficient and age-matched wild-type mice, both under basal conditions and after ischemia-reperfusion. Rolling in the postcapillary venules in SC tissue of P-selectin-deficient mice was significantly lower than that in wild-type mice under the basal conditions and post-ischemia-reperfusion (P < .05), but was not eliminated by the deletion of the P-selectin gene. No significant difference between P-selectin-deficient and wild-type mice in shear rate or leukocyte-endothelial adhesion was observed up to 24 hours after ischemia-reperfusion. These results show that P-selectin-mediated rolling is not a prerequisite for ischemia-reperfusion-induced leukocyte-endothelial adhesion in the skin.     

Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelial leukocyte adhesion molecules is unchanged in insulin-dependent diabetic BB rats

Endothelial cell injury has been implicated in the increased incidence of vascular disease associated with diabetes mellitus. In diabetic humans, elevated plasma von Willebrand Factor (vWF) has been interpreted as an indication of endothelial damage. In contrast, in an animal model of inherited insulin-dependent diabetes, the bio-breeding (BB) rat, plasma vWF levels did not differ from those in age-matched control rats during the first 7 months of diabetes although morphological evidence of mild aortic endothelial alteration or injury was observed. In the present study efforts have been made to define the endothelial alterations in BB diabetic rats compared to controls more precisely over this time period. Thus, adhesion molecules: intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were evaluated by in situ immunohistochemistry, vWF content was determined by biochemical analysis of aortic extracts and by quantitative immunohistochemistry, plasma vWF levels were measured by ELISA and vWF mRNA by RNAse protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial vWF content was significantly increased in the diabetic vessels, as observed by both approaches but the vWF mRNA content was not different from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclusion, endothelial alterations in BB rats associated with diabetes, together with the raised plasma PAI-1 levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular disease.     

The relationship between physical impairments,quality of life and disability of the neck and upper limb in patients following neck dissection

Purpose

The purpose of this study was to examine the relationship between physical impairments, quality of life and disability in patients following neck dissection, with consideration of patient and clinical characteristics.

Methods

Cross-sectional study of patients <?5 years after neck dissection for head and neck cancer. Quality of life and self-reported disability were measured with the Neck Dissection Impairment Index, Quick Disabilities of the Arm, Shoulder and Hand, and Neck Disability Index. Active neck and shoulder range of motion and isometric muscle strength were also assessed. Generalised linear modelling was used to explore relationships between variables.

Results

Eighty-four participants (68% male, median age 61 years) demonstrated reduced quality of life (median (interquartile range) score?=?76 (49, 93) from 0 (worst) to 100 (best)), and mild levels of upper limb (14 (2, 32)) and neck disability (14 (6, 28)) (from 0 (best) to 100 (worst)). Bilateral neck dissection was associated with reduced quality of life (coeff (95% CI)?=???12.49 (??24.69, ??0.29)). Post-operative chemoradiation therapy was associated with reduced quality of life (??21.46 (??37.57, ??5.35)) and neck disability (0.71 (0.10, 1.32)). Measures of shoulder flexibility or strength were associated with quality of life and self-reported disability.

Conclusions

Quality of life and musculoskeletal disability after neck dissection are associated with factors from multiple domains including physical motor function and treatment modality.

Implications for Cancer Survivors

Having reduced shoulder flexibility or strength is related to functional deficits and quality of life after neck dissection for head and neck cancer.

     

Autologous bone marrow transplantation in follicular non-Hodgkin's lymphoma before and after histologic transformation

Patients with disseminated follicular non-Hodgkin's lymphoma (NHL) are only occasionally cured with standard chemotherapy regimens. Although most of these tumors are initially responsive to chemotherapy, in 40% to 70% of patients the lymphoma will eventually transform to an NHL of higher grade malignancy and a poorer prognosis. We treated 18 patients having an original diagnosis of follicular NHL with high-dose therapy and autologous bone marrow transplantation. The lymphomas of 10 of the patients had already undergone histologic transformation and eight still had a follicular histologic pattern. The former group had been followed for a longer time from the diagnosis of NHL and had been more extensively treated with conventional chemotherapy regimens. All eight patients with follicular NHL at the time of transplantation are alive for 246+ to 1,804+ days and seven of the patients are in complete remission. In contrast, of the 10 patients in histologic transformation only 1 is alive and in CR. This reflects the inability of these patients to tolerate the high-dose chemotherapy and myelosuppression as well as resistance of their lymphoma to this therapy. This difference in survival between the two groups was highly significant (P = .002). We conclude that the outcome of patients with follicular NHL transplanted early before histologic transformation is better than for those who are transplanted later in the course of their illness. Because of the relapsing behavior of follicular NHL, a longer follow-up is necessary to prove any impact on the natural history of the disease.     

Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).

Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.     

特发性脊柱侧凸患者椎旁肌结蛋白和波形蛋白的特征表达

目的:研究表明,结蛋白和波形蛋白可反映肌肉损伤再生的情况,同时结蛋白可反应肌力的大小。比较特发性和先天性脊柱侧凸患者顶椎处凹凸两侧椎旁肌形态和结蛋白及波行蛋白的表达,探讨椎旁肌在特发性脊柱侧凸发生发展中的作用。方法:①选择2005-07/2006-11间南方医科大学南方医院脊柱骨病科收治的部分特发性脊柱侧凸患者12例,Cobb角平均73.8°;先天性脊柱侧凸患者5例,Cobb角平均36.0°;腰椎间盘突出症患者2例和胸腰椎管内占位性病变患者3例作为正常对照。所有患者年龄均在10～20岁。②对脊柱侧凸患者顶椎凹凸两侧及正常对照组患者椎旁肌进行活检,术前均签署知情同意书。③采用光镜和电镜下观察椎旁肌的形态改变;SP法分别对光镜切片的结蛋白和波行蛋白进行免疫组织化学染色,在光镜下观察蛋白表达;应用图像分析系统测量结蛋白免疫组织化学染色后反应椎旁肌蛋白表达强弱的吸光度(A)。结果:22例患者全部进入结果分析。①椎旁肌组织形态:特发性脊柱侧凸患者椎旁肌在光镜及电镜下均有病变,凹侧椎旁肌病变较重,凸侧椎旁肌相对正常。②结蛋白免疫组织化学的阳性表达:结蛋白在各组椎旁肌中均有不同程度的表达,组间比较差别显著(P<0.01)。特发性脊柱侧凸及先天性脊柱侧凸患者椎旁肌在顶椎凸侧比正常组结蛋白表达稍强(0.2727±0.0478,0.2768±0.0372,0.2429±0.0272,P<0.05),特发性脊柱侧凸及先天性脊柱侧凸患者椎旁肌在顶椎凹侧相对于正常组表达减弱(0.1898±0.0258,0.1869±0.0306,0.2429±0.0272,P<0.05)。③波行蛋白免疫组织化学的阳性表达:各组间椎旁肌肌纤维内均无波形蛋白表达。特发性脊柱侧凸与先天性脊柱侧凸患者同侧椎旁肌两组间在形态和结蛋白及波行蛋白表达无明显差别(P>0.05)。结论:特发性脊柱侧凸患者椎旁肌内波形蛋白表达均为阴性,提示椎旁肌不存在再生现象。与先天性脊柱侧凸类似,特发性脊柱侧凸患者椎旁肌结蛋白表达凸侧增强及凹侧减弱为继发性改变。