The Effect of Renal Transplantation with a Minimal Steroid Regime on Uraemic Hypertriglyceridaemia

We have studied the lipid and associated biochemical indicesin 18 renal transplant patients maintained on an alternate dayprednisolone regime. At an average 27 months following transplantationserum lipids were not significantly different from normals despitesome renal impairment in the transplant recipients. In additionthe blood sugar and plasma immunoreactive insulin levels wereelevated in transplanted patients. The intravenous fat tolerancetest (IVFTT) was not found to be different from that of normals.In some patients IVFTT was performed before and after transplantationand it was shown that K₂ (fractional removal rate of Intralipid®)improved from abnormal to normal values. Thus, it has been demonstratedthat previously abnormal lipid levels can return to normal aftertransplantation and this may be related to alternate day steroidregimes. Impaired removal of triglyceride seen in chronic renalfailure is improved by transplantation.     

佐剂性关节炎大鼠细胞因子和淋巴细胞亚群变化与可铁宁的影响

目的:观察吸烟者体内尼古丁代替主要产物可铁宁在佐剂性关节炎动物模型抗炎和调节免疫方面的作用。方法:实验于2005-10/2006-09在南方医科大学南方医院检验科及实验动物中心完成。实验动物:SD大鼠50只。实验分组和给药:随机选取SD大鼠40只注射完全弗氏佐剂,致炎建立佐剂性关节炎模型,剩余的10只SD大鼠为正常组。将40只佐剂性关节炎大鼠随机分为炎症组10只,可铁宁低、中、高剂量组各10只,可铁宁各组于佐剂注射后1周开始灌胃给药,分别给0.5,1.5,4.5g/kg体质量剂量药物,连续7d。实验评估:致炎后28d开始进行运用ELISA及流式细胞术,检测用药后对白细胞介素1β、白细胞介素2,T细胞增殖等指标(CD4 ,CD8 ,CD4 /CD8 )的影响。结果:50只大鼠全部进入结果分析。①各组大鼠血清中白细胞介素1β、白细胞介素2含量:与炎症组相比,可铁宁高、中、低剂量各组白细胞介素1β含量明显下降[(101.4±11.24),(53.40±8.23),(60.34±5.97),(72.31±8.06)ng/L,P<0.05],白细胞介素2含量明显升高[(121.3±21.2),(195.9±51.6),(174.3±40.3),(169.7±53.2)ng/L,P<0.05],且作用有一定的剂量依赖性。②各组大鼠淋巴细胞亚群CD4 ,CD8 ,CD4 /CD8 变化:造模第28天,与正常组相比,炎症组的CD4 增加,CD8 明显降低(P<0.05),CD4 与CD8 的比值显著增加(P<0.05);与炎症组相比较,可铁宁高剂量组的CD4 显著降低(P<0.05);可铁宁各组的CD8 明显增加(P<0.05),CD4 与CD8 比值显著下降,呈剂量依赖性。结论:可铁宁可调节大鼠血清中异常的白细胞介素1及白细胞介素2含量,可铁宁在试验动物水平有抗炎和免疫调节的作用。     

多普勒超声诊断移植肾排斥反应与病理检查及肾功能指标的对比分析

目的：以病理活检结果为金标准，评估多普勒超声检查对移植肾排斥反应的诊断价值。方法：选择2003—01/2006—12在中国医科大学附属第一医院器官移植科行肾移植并在术后行超声检查的患者176例，均知情同意。①实验分组：根据术后移植肾功能分为2组，移植肾功能不良组78例，其中30例次行病理活检；移植肾功能正常组98例。②实验方法及评估：对患者移植肾行多普勒超声检查，参数选择峰收缩期流速、平均舒张期流速、阻力指数及血管显示率。血管显示率的评估标准（0～5级）：0级为肾动脉及其远侧血管未显示；5级为肾各级血管均显示良好。以病理活检结果为金标准，分别选取阻力指数=0．7，0．75，0．8，0．85为诊断界值进行诊断试验。结果：169例患者进入结果分析，脱落7例。①峰收缩期流速、平均舒张期流速不呈正态分布，无法作为肾功能评价指标。30例次病理活检中共有28例次被确诊为排斥反应，急性排斥反应15例次，慢性排斥反应13例次。②肾功能正常组患者中血管显示率5级者占63．30％，4级者占36．73％。肾功能不良组患者中血管显示率4级者占41．03％，3级者占46．15％，2级者占10．30％，1级者占2．60％。③移植肾功能不良组患者阻力指数显著高于移植肾功能正常组（P〈0．01）。移植肾功能不良组患者移植肾功能恢复后阻力指数显著低于移植肾尚未恢复时（P〈0．01），其中99％以上的患者△（阻力指数）≥0.20。④界值阻力指数=0．75的诊断试验的敏感性、特异性和准确性最高，均达到100％。结论：当移植肾血管阻力指数升高至0．75以上，特别是同一患者自身对照升高超过0.2以上和或血管显示率低于4级，结合临床表现和生化结果，提示可能出现移植肾排斥反应。     

体外分离培养人脐静脉内皮及内皮下间充质干细胞

目的:建立人脐静脉内皮及内皮下间充质干细胞体外培养和扩增的方法,探讨其生物学特性,建立间充质干细胞体外培养扩增体系。方法:实验于2006-04/2006-09在辽宁医学院解剖学实验室完成。解剖细胞培养室为无菌百级培养间。正常健康产妇顺产或剖宫产的新生儿脐带由辽宁医学院附属第一医院提供,产妇及其家属均知情同意,并经医院伦理委员会批准。实验方法:①体外分离和培养贴壁细胞:无菌条件下取正常健康产妇分娩或剖宫产脐带,将其用预热PBS充分洗涤去血渍后,从脐静脉一端插入留置针,用预热PBS冲净静脉腔血后,用止血钳夹闭另一端,注入经预热至37℃的Ⅰ型胶原酶,置于37℃水浴箱中消化,30min后放出胶原酶,并用PBS冲洗血管腔,收集消化液和冲洗液,400r/min离心10min,吸弃上清液,重悬于M199培养基(含体积分数为0.15的胎牛血清,2mmol/L谷氨z酰胺,2μg/L碱性成纤维细胞生长因子,100U/mL青霉素,100U/mL链霉素)。以5×108L-1密度接种于6孔培养板中,置于37℃、体积分数为0.05的CO2饱和湿度培养箱中培养,48h后全量换液,以后每3d全量换液。待细胞80%融合时,0.25%胰酶消化,按1×108L-1传代培养。②间充质干细胞生长曲线的测定:取传代培养细胞,按2×107L-1密度接种于24孔培养板内,每天取3孔,将细胞消化计数,连测8d,绘制间充质干细胞生长曲线。③间充质干细胞表面抗原检测:在24孔塑料培养板内放置无菌的盖玻片,每孔中种植108L-1第2代细胞悬液1mL。采用免疫细胞化学方法进行细胞表面抗原检测。结果:①间充质干细胞的形态学观察:接种的细胞48h后细胞完全贴壁生长,其镜下形态有呈椭圆形、多角形的内皮细胞以及呈梭形的成纤维样细胞,有的形成漩涡状生长的集落。②间充质干细胞生长曲线的分析:传代培养的潜伏期约为24～36h,细胞倍增时间约为30～36h,对数增殖期约为二三天,对数增殖期后第5天进入平台期。③间充质干细胞表面抗原特性:免疫细胞化学分析结果显示,间充质干细胞表面抗原cd166、cd44阳性,而vWF阴性,说明分离获得的细胞具有间充质干细胞的特点。结论:所建立的分离和培养方法可获取人脐静脉黏附细胞中一组独特的细胞群,具有间充质干细胞的生物学特性。     

In vivo relevance for platelet glycoprotein Ibα residue Tyr276 in thrombus formation

Summary.  Background:  Platelet glycoprotein (GP) Ib-IX-V supports platelet adhesion on damaged vascular walls by binding to von Willebrand factor (VWF). For several decades it has been recognized that the α-subunit of GP (GPIbα) also binds thrombin but the physiological relevance, if any, of this interaction was unknown. Previous studies have shown that a sulfated tyrosine 276 (Tyr276) is essential for thrombin binding to GPIbα. Objectives:  This study investigated the in vivo relevance of GPIbα residue Tyr276 in hemostasis and thrombosis. Methods:  Transgenic mouse colonies expressing the normal human GPIbα subunit or a mutant human GPIbα containing a Phe substitution for Tyr276 (hTg^Y276F) were generated. Both colonies were bred to mice devoid of murine GPIbα. Results:  Surface-expressed GPIbα levels and platelet counts were similar in both colonies. hTg^Y276F platelets were significantly impaired in binding α-thrombin but displayed normal binding to type I fibrillar collagen and human VWF in the presence of ristocetin. In vivo thrombus formation as a result of chemical damage (FeCl₃) demonstrated that hTg^Y276F mice have a delayed time to occlusion followed by unstable blood flow indicative of embolization. In models of laser-induced injury, thrombi developing in hTg^Y276F animals were also less stable. Conclusions:  The results demonstrate that GPIbα residue Tyr276 is physiologically important, supporting stable thrombus formation in vivo .     

The efficacy of subcutaneous recombinant human erythropoietin in the correction of phlebotomy-induced anemia in autologous blood donors

The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3- week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 +/− 1.0 g/dL [140 +/− 10 g/L]) was completely recovered before surgery (14.0 +/− 1.6 g/dL [140 +/− 16 g/L]) in the EPO group, while a decrease from 13.8 +/− 1.1 to 12.2 +/− 1.3 g per dL (138 +/− 11 to 122 +/− 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 +/− 29 micrograms per L in the EPO group and to 54 +/− 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

Anxiety and depression in children and adolescents with spinal cord injuries

Aim  To determine the levels of anxiety and depression in young people with spinal cord injuries (SCI) and their associated factors and outcomes.
Method  Children and adolescents aged 7 to 17 years at interview who had sustained SCI at least 1 year before the study were assessed using the Children's Depression Inventory, the Revised Children's Manifest Anxiety Scale, the Pediatric Quality of Life Inventory, the Children's Assessment of Participation and Enjoyment, and a demographic questionnaire designed for the study.
Results  The 118 participants (61 males, 57 females) had a mean age of 12 years 4 months, SD 3y 1mo, range 7-17y. Mean age at injury was 5 years 11 months, SD 4y 11m, range 0-16y; 89 participants (75%) had paraplegia and 29 (25%) had tetraplegia. Fifty-seven (52%) had complete injuries and 52 (48%) had incomplete injuries according to the American Spinal Injury Association impairment scale. Thirteen participants (13%) reported significant symptoms of anxiety, and seven (6%) reported significant levels of depression, which were comparable to the normative population. Age, race, and sex were not associated with anxiety or depression, but participants with shorter duration of injury were more likely to be anxious, and those with less functional independence were more likely to be depressed. Only one dimension of participation was associated with anxiety and depression, but all aspects of quality of life were decreased among those with anxiety or depression.
Interpretation  The levels of anxiety and depression in young people with SCI are comparable to the normative range. When anxiety and depression occur they are associated with reduced levels of quality of life.     

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease: analysis of nationwide experience in Scotland (2004–2008)

Background  Adalimumab is a second generation humanized anti-tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn's disease (CD).
Aims  To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting.
Methods  We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4-year period (2004–2008).
Results  A total of 98 patients received adalimumab - 100.5 patient follow-up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1-year follow-up, with 30% and 55% requiring dose escalation to weekly therapy at 1-and 2-year follow-up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively).
Conclusions  Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy- and disease-related risks of serious complications.