异基因造血干细胞移植后巨细胞病毒的检测及临床意义

目的 为了降低异基因造血干细胞移植（allo-HSCT）后巨细胞病毒（CMV）感染的相关死亡率，寻求一种更快捷、更特异的诊断CMV感染的分子生物学方法。方法 2001年4月至2003年4月，从79例接受异基因造血干细胞移植的患者中采集了135份外周血标本。采用巢式聚合酶链反应（nested-PCR）方法检测患者外周血中CMVgB DNA，阳性标本做酶切分型，部分行序列测定。结果CMVgB DNA检测中有42例患者（53．9％）的66份标本（48．9％）阳性；对其中阳性患者的45份标本进行了酶切分型，结果 CMV gB1型21例（46．7％），CMV gB2型14例（31．1％），CMV gB3型7例（15．6％），CMV gB4型3例（6．7％）。先后有2种型别的CMV感染者有3例（3．8％）。经分析，CMV gB阳性和CMV gB阴性患者GVHD的发生率分别为81．0％和32．4％（P＜0.01）；CMV gB1、gB2、gB3以及gB4型Ⅱ～Ⅳ度急性GVHD及慢性GVHD的发生率分别为：81．0％、50．0％、42．9％和0。结论 Nested-PCR方法可快捷特异地检测CMV感染。CMVgB1、2型中，重度急性GVHD和慢性GVHD发生率较高。CMV gB基因分型检测可有效地指导临床抗病毒治疗，且对移植后患者的临床转归有一定的预测价值。     

三维适形放射治疗门静脉癌栓23例

目的探讨三维适形放射治疗门脉癌栓的近期疗效.资料与方法 23例均为肝癌介入治疗后出现门静脉癌栓,其中原发性肝癌8例,转移性肝癌15例,所有病人均在介入治疗2～4次后出现门静脉癌栓.采用三维适形照射的方法,每例均设定4～6个非共面野,单次照射剂量3～7Gy,6～15次,每日或隔日照射,总剂量42～48 Gy.结果总有效率3个月为82.6%,6个月为95.7%,Kaplan-Meier分析法,1、2、3年生存率分别为82.6%、43.5%和26.1%,中位生存期14个月.Cox回归分析提示Child-Pugh肝功能分级和单次照射剂量与预后有关.结论三维适形放射治疗肝癌介入后门静脉癌栓是一种方法简单、病人易于接受、近期疗效显著的可行性方法,值得临床推广.     

致敏供者淋巴细胞输注对受者免疫功能重建及移植物抗宿主病发生率的影响

目的探讨非清髓异基因外周血造血干细胞移植后致敏供者淋巴细胞输注(DLI)对受者免疫重建及移植物抗宿主病(GVHD)发生率的影响。方法以C57BL/6小鼠(H-2b)为受鼠, BALB/c小鼠(H-2d)为供鼠,建立异基因外周血造血干细胞移植模型(实验组),移植当天受者接受60Coγ射线全身照射,移植后第2天腹腔注射环磷酰胺200 mg/kg。以不行造血干细胞移植,仅行γ射线全身照射和环磷酰胺腹腔注射的正常C57BL/6小鼠为对照。实验组存活小鼠在移植后第28天分别接受致敏供鼠淋巴细胞输注(n=8)、未致敏供鼠淋巴细胞输注(n=8),另有6只不输注供鼠淋巴细胞。移植后检测受者异基因嵌合率,观察GVHD的发生情况以及T淋巴细胞亚群变化,并行供受者间以及供受者与第三方小鼠(昆明鼠)间的单向混合淋巴细胞反应。结果实验组受鼠SRY基因均为阳性,嵌合率为(30.881±3.962)%。DLI后,接受未致敏DLI者均出现不同程度的GVHD,死亡3只(7.5%,3/8),而接受致敏DLI者无明显GVHD及死亡者。移植后45 d,接受致敏DLI者的CD8 T淋巴细胞明显高于正常C57BL/6小鼠(P<0.05),而接受未致敏DLI者的CD8 T淋巴细胞与正常对照的差异无统计学意义(P>0.05),至移植后60 d,接受DLI者的T淋巴细胞亚群接近正常(P>0.05);对照组T淋巴细胞亚群持续低于正常对照(P<0.05)。实验组小鼠淋巴细胞对供者淋巴细胞刺激的反应性均下降(P<0.01),以接受致敏DLI者最明显,而对昆明鼠淋巴细胞刺激的反应性维持正常水平。结论造血干细胞移植后输注致敏供者的淋巴细胞能促进受者的免疫功能重建,并可减少GVHD的发生。     

Use of a sensitive enzyme immunoassay for human thyrotropin in the diagnosis of hyperthyroidism

A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia.     

EFFECTS OF p53 GENE THERAPY COMBINED WITH CYCLOOXYGENASE-2 INHIBITOR ON CYCLOOXYGENASE-2 GENE EXPRESSION AND GROWTH INHIBITION OF HUMAN LUNG CANCER CELLS

Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. The antitumor effect of selective cyclooxygenase （COX）-2 inhibitors has been demonstrated in preclinical studies. However, no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells. Methods We evaluated the effects of recombinant adenovirus-p53 （Adp53） gene therapy combined with selective CADX-2 inhibitor on the proliferation, apoptosis, cell cycle arrest of human lung adenocarcinoma A549 cell line, and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression. Results Ad-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression. Conclusions Significant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition, apoptosis induction and suppression of COX-2 gene expression. This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.     

Occupational dermatitis from Synacril Red 3B liquid (Cl Basic Red 22)

A carpet factory worker, exposed to a number of different dyes, developed a severe hand dermatitis. The handling of warm, wet and freshly-dyed yarn with unprotected hands was thought to have caused the onset of dermatitis. Patch testing indicated that the patient was sensitive to only one of the dyes handled, namely Synacril Red 3B liquid, which is based on the single dyestuff Basic Red 22 (CI 11055). Chemical analysis revealed the dyestuff to be of high purity (greater than 95%), suggesting that sensitization was caused by the Basic Red 22 dyestuff itself and not by an avoidable impurity.     

Die Insuffizienz der intraabdominellen Infektabwehr bei der eitrigen Peritonitis — Folge einer gestörten Fremdkörperopsonierung

Summary Despite a high concentration of serum proteins and intact phagocytes peritonitis exudates contain a large number of viable, pathogenic bacteria. The reason for this biological paradox is unknown. Our investigations reveal a pronounced defect in humoral opsonization of foreign particles in peritonitis exudate. We evaluated a modified chemiluminescence system allowing the determination of opsonic activity in serum and exudate. In serum we found a close correlation between opsonic activity and immunologically measurable levels of C₃-complement and IgG. In purulent peritonitis exudates, however, the actual opsonizing activity was much less than expected according to the opsonin concentrations. We found a pronounced difference between immunologically determined opsonin levels and impaired opsonic function. Employing crossed immunoelectrophoresis massive C₃-splitting into smaller fragments could be demonstrated in peritonitis exudates. In these exudates we found very high concentrations of granulocyte proteolytic (elastase) and oxidative (myeloperoxidase) enzymes which may lead to a functional destruction of opsonins followed by impaired opsonization in peritonitis exudate. The great number of bacteria and foreign particles in addition can cause a pronounced physiological consumption of complement components. The almost complete breakdown of intact C₃-complement in intraabdominal exudate explains the deficient host defence in patients with severe peritonitis.

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Abkürzungsverzeichnis CL Chemilumineszenz - IgG Immunglobulin G - OK Opsonierungskapazität     

Metabolic and hormonal blood flow modeling in patients with coronary heart disease: In vitro and clinical study

The blood flow pattern investigations are of great importance in coronary blood flow destabilization pathogenesis understanding, and consequently in acute coronary event (ACE) risk stratification in patients with coronary heart disease. The aim of the study was to research the principal hormonal and metabolic blood flow regulative aspects and its structure in patients with ischemic heart disease and the contribution to cumulative ACE risk.A total of 182 patients with stable angina pectoris were included in the prospective study (2000–2006). Complex clinical examination, biochemical tests and blood tests were performed. Whole-blood (WB) viscosity, erythrocyte aggregation and deformation ability, WB suspension stability, and initial erythrocytes disaggregation parameter were studied. Dynamic characteristics of blood flow were obtained in the experiment.Received results allow marking the principle components of blood flow pattern with proven high prognostic value of ACE in patients with ischemic heart disease. ACE risk stratification program was developed.     

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.