Cerebrospinal fluid-filtration reduces TNF alpha in bacterial meningitis-CSF

A 37 year old male was admitted with the diagnosis of bacterial meningitis. Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical condition did not suggest severely raised intracranial pressure, there were no localizing signs and symptoms. CSF was turpid, with 20.100/3/mm³, mainly polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall-filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm³, TNF-alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient could be discharged without sequelae. CSF filtration may be a highly effective method to reduce from the CSF pathogenetically important cytokines, such as TNF-alpha, being responsible for intrathecal/meningeal inflammatory processes and triggered by cell-wall components of bacteria, e.g. pneumococci.     

α2-巨球蛋白基因I1000V多态性与散发阿尔茨海默氏病的关联研究

目的近年来有研究发现α2-巨球蛋白基因(α2-macroglobulin，A2M)Ile1000Val多态与阿尔茨海默氏病(Alzheimer’s disease，AD)发病有关联，但也有相悖的研究结果报道。因此．我们利用较大的样本，观察了A2M基因Ile1000Val多态在广州及成都地区汉族老年人中的分布，并探讨其与散发AD的相关性。方法以广州地区257例散发AD患者和242名正常老年人、成都地区112例散发AD患者和113名正常老年人为对象进行病例一对照研究。用聚合酶链反应一限制性片段长度多态性方法分析A2M基因11000V多态性和载脂蛋白E基因(apolipoprotelnE，apoE)多态性。结果(1)在两地合并样本中，AD患者与对照组中等位基因A2M-1000V的频率分别为7．7％与8．7％，广州与成都地区AD患者与对照组中A2M基因I1000V多态的分布差异无统计学意义。(2)散发AD无论按是否伴有apoE—ε4或按发病年龄分成不同亚组后，A2M基因I1000V多态的分布在病例组与对照组之间差异无统计学意义。结论广州与成都汉族人群中A2M基因I1000V多态与散发AD不具有关联。     

Serum {alpha}2-macroglobulin in haemodialysis patients: baseline and kinetic studies

The pathogenesis of dialysis related amyloidosis remains unresolveddespite the identification of ß₂-microglobulin (ß₂M)as the major protein constituent, as well as other proteinsbeing present in the deposits. Among the latter we have assessedthe serum concentrations of ₂-macroglobulin (₂M) both in thebaseline stage and during the haemodialysis (HD) procedure.We have also assessed the influence of the membrane on ₂M kinetics. Fifteen HD patients with histologically proven dialysis-relatedamyloidosis (DRA group) and 15 HD patients clinically and radiologicallyconsidered dialysis-related amyloidosis free (control group)were included in the baseline study. Blood was sampled the daybefore the second dialysis of the week and ₂M, ß₂Mand ₁, antitrypsin were determined along with the routine biologicalanalysis of these patients. Serum ₂M was greater in dialysis-relatedamyloidosis than in control patients (t = 2.35; P<0.026).Serum ß₂M was similar in both groups. The serum ₂Mand ß₂M correlated in patients with dialysis-relatedamyloidosis (r = 0.64; P<0.01), while no correlation wasfound in controls (r = 0.17; NS). Stepwise analysis taking thepresence of dialysis-related amyloidosis as the dependent variableretained the serum ₂M concentration as the first variable inthe model (F = 4.4; partial r = 0.38; P<0.046). The sameproteins were determined in another group of seven patients,before and hourly during HD as well as 2 and 8 h after the endof HD during nine consecutive dialyses (3 cycles of 3 HD eachusing AN69 and cuprophane membranes in a crossover design).Serum ₂M significantly increased from hour 3 and continued toincrease 2 hours post-HD (+11% and +9% with AN69 and cuprophanerespectively; P<0.001). Total proteins peaked at hour 4 (+4% and +3% P<0.01) and decreased after HD. Serum ß₂Msignificantly decreased with AN69 HD ( – 29% P<0.001)and remained unchanged during cuprophane HD. In conclusion, significant increases in serum ₂M are observedimmediately after and during the early post-dialysis periods,regardless of the membrane used. Further, serum ₂M correlateswith ß₂M only in patients with dialysis-related amyloidosis,and this variable was retained in the multivariate regressionanalysis to predict dialysis-related amyloidosis. Although thebaseline results require confirmation with larger studies, wepostulate that the present results are of relevance for dialysis-relatedamyloidosis pathogenesis since ₂M, previously identified indialysis related amyloid deposits, is closely related to acute-phasereactant proteins, and interacts with the main infiltratingcells of the deposits (macrophages). ₂M modifications couldrepresent a new manifestation of the inflammatory response tothe haemodialysis procedure.     

糖尿病和糖尿病肾病患者白蛋白、β_2-微球蛋白、粘蛋白含量及l~(131)邻碘马尿酸钠肾图分析

[目的 ]观察糖尿病及糖尿病肾病时尿白蛋白、β2 微球蛋白、粘蛋白含量及I13 1 邻碘马尿酸钠肾图曲线变化关系 .[方法 ]用放射免疫检测法测定白蛋白、β2 微球蛋白、粘蛋白 ,I131 邻碘马尿酸钠肾图采用核多功能测定仪的两个放射性探测器直接在体表分别探测两肾区的时间 放射性曲线 .[结果 ]78例糖尿病患者中尿白蛋白、血尿 β2 微球蛋白和尿粘蛋白均增高 ,但血粘蛋白无变化 ;18例行I131肾图 ,其中有 1例肾图曲线的C段排泄有变化外 ,其余正常 .40例糖尿病肾病患者中尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白明显增高 ,血粘蛋白改变不明显 .I131 邻碘马尿酸钠肾图曲线随着血糖及尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白含量的增高而出现不同类型的改变 .[结论 ]尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白对糖尿病肾病具有早期诊断价值 ,与此同时结合I131 邻碘马尿酸钠肾图 ,可更全面了解和评价全肾功能损伤情况     

Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.     

SDS-琼脂糖凝胶电泳分析蛋白尿来源的临床意义

目的分析尿蛋白成分来鉴别蛋白尿来源。方法应用十二烷基磺酸钠-琼脂糖凝胶进行非浓缩尿蛋白电泳分析49例蛋白尿患者的尿蛋白成分。结果在肾后性蛋白尿中往往可以检测到巨球蛋白等一类大分子蛋白,而在肾性则往往缺乏。并且以巨球蛋白作为鉴别蛋白尿的标准,其敏感性和特异性均达到95.8%。结论该方法客观性强,诊断符合率高,重复性好,简便快速,值得临床应用。     

Challenge-induced plasma exudation and mucinous secretion in human airways

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P<0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways.     

Treatment of endothelium with the chemotherapy agent vincristine affects activated protein C generation to a greater degree in newborn plasma than in adult plasma

INTRODUCTION: Activated protein C (APC) is well-established as a physiologically important anticoagulant. During development, plasma concentrations of protein C and alpha(2)macroglobulin, factors involved in APC generation, differ from adult levels. Chemotherapy drugs can perturb endothelial expression of PC-activating receptors. This study examines the effect of chemotherapy treatment of endothelium on APC generation in newborn and adult plasma. MATERIALS AND METHODS: APC generations were initiated on endothelial cells treated with vincristine or media by recalcifying defibrinated plasma with buffer containing thromboplastin. APC generation was terminated by mixing timed subsamples into FFRCMK-EDTA or heparin, followed by EDTA. APC-PCI and APC-alpha(1)AT were assayed by ELISA. APC-alpha(2)M was measured chromogenically. Since heparin converts free APC to APC-PCI, the difference between APC-PCI detected in heparin subsamples and APC-PCI detected in FFRCMK-EDTA subsamples gave the free APC. Cellular expression of EPCR and TM were measured by flow cytometry and Western blot. RESULTS: Vincristine-treated endothelium decreased free APC generation in newborn plasma to a greater degree than in adult plasma. APC-PCI levels in both adult and newborn plasma were unaffected by chemotherapy. Vincristine treatment reduced levels of APC-alpha(1) AT and APC-alpha(2) M to a greater degree in newborn plasma versus adult plasma. Expression of EPCR was reduced in cells treated with vincristine. Conversely, TM was reduced on the cell surface, but increased in whole cell lysates. CONCLUSIONS: The differential response of newborn and adult plasma PC components to chemotherapy-mediated changes in cell surface components may be a factor in the increased risk of thrombosis in children receiving chemotherapy.     

Prognostic potential of a PSA complex in sera of prostate cancer patients with alpha2-macroglobulin deficiency

We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). In order to elucidate the relative proportions of free and a prostate-specific antigen (PSA) complex in PCa patients with alpha2M deficiency, we have assessed serum alpha2M and total PSA levels, and ratios of free PSA to total PSA (F/T ratios) at each stage of PCa. Moreover, the PSA reactivity profile was determined on fractionated serum specimens of PCa patients using high-performance liquid chromatography (HPLC) using a TSKG-3000 SWXL column. Measurement of alpha2M concentration was performed by laser-nephelometry. PSA levels were determined by enzyme immunoassay, free PSA by radioimmunoassay. In those PCa patients with alpha2M deficiency, serum alpha2M and F/T ratios were lower, whereas PSA levels were higher when compared with those PCa patients without alpha2M deficiency (P<0.05). PSA elution profiles on HPLC columns revealed two major peaks. The proportion of PSA-antichymotrypsin (PSA-ACT) increased, whereas the proportion of free PSA decreased in PCa patients with alpha2M deficiency as compared with those PCa patients without alpha2M deficiency. F/T ratios were significantly lower in PCa patients with alpha2M deficiency than in those PCa patients without alpha2M deficiency. PSA-ACT and F/T ratio may be useful for monitoring bone metastasis in PCa.