Logistic回归和ROC曲线分析多种肿瘤标志物在结直肠癌中的诊断价值

目的:应用Logistic回归和ROC曲线探讨CEA、CA199及CA50在结直肠癌诊断中的应用价值.方法:结直肠癌患者75例,良性结直肠病患者35例,正常人49例,分别应用化学发光免疫分析测定CEA,电化学发光免疫分析测定CA199,免疫放射分析测定CA50,通过ROC曲线分析CEA、CA199、CA50及各种Logistic回归结果的ROC曲线下面积(AUC).结果:结直肠癌-良性结直肠病中,CA50的AUC要高于CA199的AUC,而CEA、CA50两项联合诊断结直肠癌的AUC(0.875)要高于CEA、CA199、CA50三项联合诊断的AUC(0.604),且CEA、CA50两项联检诊断的AUC高于CEA、CA199或CA50任意单一检查的AUC.在结直肠癌-正常对照组中,三项肿瘤标志物联检的AUC(0.866)均高于三项肿瘤标志物单一检查的AUC,无论在结直肠癌-正常对照组中还是结直肠癌-良性结直肠病中CEA的AUC都高要于CA199或CA50.结论:CEA在诊断结直肠癌有一定的临床应用价值,CA50联合CEA检测可为临床鉴别良恶性结直肠病提供有效的参考,而CEA、CA199及CA50三者联检对鉴别良恶性结直肠病的意义不大.作为一种统计手段,Logistic回归可改善诊断的灵敏度和特异性.     

Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature infants (4 cases) were immunostained with antibodies against sialyl glycoproteins (anti-KL-6 and anti-sialyl MUC1 antibodies). Cytoplasmic expression of KL-6 and sialyl MUC1 was distinctive in the chromophobe RCC and renal oncocytoma cells, and in the intercalated cells in collecting duct epithelia. Apical-surface staining of these sialyl glycoproteins was predominantly observed in clear RCC, in the epithelia of the distal tubule and collecting duct, and in the neonatal renal proximal tubule, but not in those of the adult renal proximal tubule. The above-mentioned observations provide additional evidence for similar phenotypic profiles of chromophobe RCC and renal oncocytoma, and the intercalated cells in collecting ducts and the oncofetal expression of sialyl glycoproteins in clear cell RCC. KL-6 is a potential tumor marker for renal tumors.     

Expression of the Cell Cycle Inhibitor p27KIP1 Is a New Prognostic Marker Associated with Survival in Epithelial Ovarian Tumors

This case-control study was designed to identify factors associated with long-term survival. We examined two groups of patients with epithelial ovarian cancer, one group of long-term survivors (>5 years) and one group of short-term survivors (<2 years), for levels of expression of p53 and p27^KIP1 proteins (as both proteins have been shown to be independent prognostic markers in tumors other than ovary) and the relationship with patient survival. Our findings show that p27^KIP1 expression, in contrast to p53 expression, is positively associated with long-term survival in univariate analysis (P = 0.001), in analyses stratified by residual disease (P = 0.02) or performance status (P = 0.02), the two strongest prognostic factors for ovarian cancer, as well as multivariate analysis (P = 0.002) adjusting simultaneously for age, tumor stage, residual disease, performance status, and grade of differentiation. Therefore, immunostaining for levels of p27^KIP1 expression may have potential as a new prognostic factor in the management of ovarian cancer.     

The Phenotypic Characterization of A13/BACii, a Novel Bovine Chondrocytic Cell Line with Differentiation Potential

In cartilage research bovine articular cartilage is used as an alternative to human tissue. However, animal material is subject to availability and primary cultures undergo senescence, limiting their use. Here we report the immortalization of primary bovine chondrocytes, which could be used as a surrogate for freshly isolated chondrocytes. Chondrocytes were isolated from cartilage explants and immortalized using 1.0 μg/ml benzo[alpha]pyrene. For 3-dimensional culture, chondrocytes were resuspended in 0.5% low-melt agarose at high density (HD) and cultured for 24 h prior to determining changes in expression profile and morphology. A13/BACii chondrocytes acquired a 'flat' irregular morphology and a foetal-like cell volume (1,509.59 ± 182.04 μm(3)). The human cell line C-20/A4 showed a statistically similar volume and length to A13/BACii. Two-dimensional-cultured A13/BACii expressed elevated levels of type I collagen (col1), reduced levels of type II collagen (col2) compared to freshly isolated chondrocytes and an overall col2 to col1 expression ratio (col2:col1) of 0.11 ± 0.01. Upon 3-dimensional encapsulation, there was a significant rise in col2 expression in both A13/BACii and C-20/A4, suggesting a capacity for redifferentiation in both cell lines with a return of col2:col1 values of A13/BACii to values previously observed in primary chondrocytes. A13/BACii chondrocytes expressed aggrecan, matrix metalloproteinase (MMP)-3, MMP-9 and MMP-13, further supporting indications of the differentiated phenotype. Here we report the creation of a novel chondrocytic cell line and demonstrate its strong potential for redifferentiation upon HD 3-dimensional encapsulation, providing an alternative to conventional dedifferentiated cell lines and primary culture.     

Elevated Expression of Transmembrane IL-15 in Immune Cells Correlates with the Development of Murine Lupus: a Potential Target for Immunotherapy Against SLE

Presentation in trans by the Interleukin-15 receptor α chain (IL-15Rα) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Ig κ chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15Rα-Fc) between the extracellular domain of hIL-15Rα and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in macrophages, activated T cells and B cells from 6-month-old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL-15Rα-Fc was able to block the T cell stimulating and anti-apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro . Intravenous administration of hIL-15Rα-Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL-15 activity in vivo may be an effective way of treating SLE.     

Serial Measurement of WT1 Expression and Decrement Ratio Until Hematopoietic Cell Transplantation as a Marker of Residual Disease in Patients with Cytogenetically Normal Acute Myelogenous Leukemia

Using real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD–negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD–negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT.     

The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Torque teno virus (TTV) is a nonenveloped, single-stranded, circular DNA virus of the family of Anelloviridae. The first contact with TTV usually occurs in early childhood, followed by persistent infection in bone marrow and lymphocytes. Increased levels of TTV-DNA are found in the serum in various states of immune deficiency. The objective of this study was to assess if monitoring of TTV viremia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a predictive marker for immune-related clinical complications. In a retrospective study, 2054 whole-blood samples from 123 patients were tested for viral loads of TTV-DNA by real-time PCR within 345 days after allo-HSCT. We enrolled all patients who underwent allo-HSCT between September 2015 and April 2018. Clinical and laboratory data were collected and statistically analyzed. Patients with an underlying lymphatic malignancy had significantly higher torque teno (TT) viral loads compared with patients with an underlying malignant myeloid disease (P < .05). Complete remission before allo-HSCT correlated significantly with higher TT viral loads after allo-HSCT (P < .05). Myeloablative conditioning regimens led to significantly higher TT viral loads than reduced-intensity conditioning regimens (P < .05). A higher anti-thymocyte globulin (ATG) dose was associated with a significantly higher TT viral load. We did not observe any significant differences of TT viral load correlating with accompanying clinically relevant events such as virus reactivations (cytomegalovirus, Epstein-Barr virus, Adenovirus), acute graft-versus-host disease (aGVHD), relapse, or death. TT viral load after allo-HSCT did weakly correlate with T cell, T suppressor cell, T helper cell, and natural killer and B cell count. Although statistically significant differences between study groups were observed, virus reactivations, aGVHD, and clinical outcomes could not be predicted by monitoring TTV viremia. Therefore, TTV seems not to be suitable as a marker for the degree of immunosuppression or as a prognostic marker for clinically critical events in patients after allo-HSCT.     

Detection of Genomic Amplification of the Human Telomerase Gene TERC,a Potential Marker for Triage of Women with HPV-Positive,Abnormal Pap Smears

The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.Cervical carcinoma is the second most common malignancy among women world-wide.¹ The introduction of screening programs based on cytological examination of cervical smears resulted in a significant decrease in both incidence and mortality rates.² The most common cervical cancer type is squamous cell cervical carcinoma.³ Infections with high-risk human papillomavirus (HR-HPV) are almost invariably found in women with neoplastic disease and progression from low-grade to high-grade dysplasia, and invasive disease is very rare in the absence of HR-HPV.⁴ However, transient HPV infections that do not result in the development of high-grade dysplasia are common in young, sexually active women.The causal relationship between HR-HPV infection and cervical cancer has made the detection of the virus an attractive approach to identify women at risk of developing cervical cancer.⁵ However, it has also become increasingly evident that other factors, in addition to HR-HPV per se, are required for cervical carcinogenesis, since only rarely will women infected with HR-HPV eventually develop cervical cancer. Therefore, biomarkers strongly associated with the propensity of low-grade lesions to progress to high-grade lesions and cancer would be of great value for the individualization of the clinical management of women with abnormal Pap smears.⁶The expression of the HPV protein E7 triggers the activation of the cyclin-dependent kinase inhibitor p16^INK4a, which has been explored for its diagnostic potential.⁷ In normal cells, p16 expression is essentially undetectable by immunocytochemistry. It is possible that such staining will not only improve the chances of detecting premalignant cells, but also aid in the distinction between premalignant and reactive atypia.⁸In addition to infection with HPV and its consequent expression of p16, the majority of cervical carcinomas carry extra copies of the long arm of chromosome 3 and with it genomic amplification of the RNA component of the human telomerase gene (TERC), which resides on cytoband 3q26.^9,10 Therefore, genomic amplification of this gene is likely to play a central role in progression from low-grade dysplasia to high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. In a previous study, we showed that progression is never observed in the absence of genomic amplification, and, inversely, extra copies of this gene are not present in lesions that spontaneously regress.¹¹The aim of the present study was to validate these findings among women undergoing testing for cervical cancer following an abnormal Pap smear at population-based screening, and to correlate the amplification status of TERC with the histological evaluation of concordant biopsies. Genomic copy numbers of TERC and the oncogene MYC were determined on liquid based cytology (LBC) slides using fluorescence in situ hybridization (FISH), and the findings were systematically compared with HPV status, p16 protein expression, and the results of cytological screening and histopathological diagnoses.     

良、恶性B淋巴细胞膜HLA-DR和Mg~(++)-ATP酶的电镜观察

用HLA-DR单克隆抗体和ABC免疫酶标及Mg~(++)-ATP酶组化技术,在电镜下观察B细胞性恶性淋巴瘤及非肿瘤性淋巴组织标本各4例,成功地观察到良、恶性B淋巴细胞膜上均有电子致密黑色的HLA-DR抗原和ATP酶反应物沉淀。良性B细胞膜上反应物量少,分布均匀,恶性B淋巴细胞膜上反应物量多呈不均匀的串珠状分布,这为研究肿瘤性B淋巴细胞在超微结构水平上提供了二种标记物的形态学依据。     

Design,Preparation, and Characterization of Thermoresponsive Hybrid Nanogels Using a Novel Ulvan‐Acrylate Crosslinker as Potential Carriers for Protein Encapsulation

The aim of the present study is the design and development of thermoresponsive nanogels based on ulvan, a sulphated heteropolysaccharide of algal origins with unique biological and chemical properties. Hybrid nanogels are successfully synthesized by means of UV‐initiated radical copolymerization of N‐vinylcaprolactam with an ulvan derivate as a novel crosslinker. In nanogels, the ulvan‐grafted poly(N‐vinylcaprolactam) chains represent the thermoresponsive component. The most promising candidates, selected after a thorough physical–chemical characterization of nanogels in terms of size and responsivity to thermal variation at physiological conditions, are loaded with bovine serum albumin (BSA) as model bioactive compound. The developed nanogels display BAS loading efficiency values similar to those obtained by using synthetic crosslinkers, and thus indicating the suitability of the developed ulvan‐acrylate to act as novel macromolecular crosslinker for thermoresponsive nanogels preparation.     

Imipenem/Cilastatin with or without Glycopeptide as Initial Antibiotic Therapy for Recipients of Autologous Stem Cell Transplantation: Results of a Spanish Multicenter Study

We analyzed the efficacy of imipenem/cilastatin alone (group I, 197 patients) or in combination with a glycopeptide (group I + G, 231 patients) as first-line antibiotic therapy for 2 consecutive cohorts of autologous stem cell transplantation (ASCT) recipients with febrile neutropenia. From June 2001 to June 2002, patients received imipenem/cilastatin (500 mg/6 hours), and from July 2002 to December 2003, they received imipenem/cilastatin as for group I plus a glycopeptide (vancomycin, 1 g/12 hours or teicoplanin, 400 mg/day). Fever of unknown origin accounted for 33.5% of episodes (66 patients) in group I and 50% of episodes (116 patients) in group I + G (P = .005). Bacteremia occurred in 55 patients (28%) in group I and in 51 patients (22%) in group I + G (P = .16). Resolution of fever without modification of the therapy regimen was observed in 108 patients (55%) and 159 patients (69%) in groups I and I + G, respectively (P = .003). The median interval to defervescence (4 days) and overall mortality were similar between groups. Inclusion of a glycopeptide in the initial antibiotic regimen for febrile neutropenia results in a higher success rate without modifying the regimen. However, glycopeptide inclusion does not improve the interval to defervescence or mortality rate.     

Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes : Survivin Expression Overlaps with Stem Cell Markers

Survival has been implicated to play an important role in various pathophysiological processes. However, because of a lack of appropriate animal models, the role and dynamic expression of survivin during pathophysiology are not well defined. We generated a human survivin gene promoter-driven luciferase transgenic mouse model (SPlucTg) so that dynamic survivin gene activity can be monitored during various pathophysiological conditions using in vivo imaging. Our results show that, consistent with survivin positivity in testis, luciferase activity in normal SPlucTg mice was detected in the testis of male mice. Furthermore, similar to the known requirement of transient expression of survivin for pathophysiological responses, we observed a transient luciferase expression in castrated SPlucTg male mice after supplement of androgen. Significantly, it was reported that survivin expression turns on during mouse liver injury and regeneration; a transient and dose-dependent luciferase expression in the mouse liver was observed after administration of carbon tetrachloride into SPlucTg mice. We further demonstrated that luciferase activity closely correlates with endogenous survivin expression. We also demonstrated that only a subset of cells expresses survivin, and its expression overlaps with the expression of several stem cell markers tested. Thus, we have generated a unique animal model for analysis of diverse pathophysiological processes and possible stem cell distribution/activity in vivo.Evidence indicates that survivin, an inhibitor of apoptosis (IAP) family protein and a promoter of cell cycle and mitosis,^1,2,3 plays an important role in cancer initiation⁴ and angiogenesis,^5,6,7 tumor progression, drug/radiation resistance,⁸ and tumor relapse.^3,9 Survivin may also play a role in other pathophysiological processes.^10,11,12 These include embryonic development, hematopoietic cell survival and proliferation, T-cell development, multiple sclerosis, brain pathology, and pathophysiology of other organs including liver, pancreas, gastrointestine, testes, endometrium, and placenta.¹¹ However, studies indicated that the behavior of survivin expression, subcellular localization, and/or gene regulation appear to be different during normal tissue turnover or repair versus cancer initiation and progression.¹¹ Furthermore, in some cases, normal cell division, survival, and development happen in the absence of survivin¹³ or with differential requirement of survivin.¹⁴ Additionally, because of increased expression of survivin in cancer, the interaction of survivin molecules with other proteins may differ from normal cells and/or may exclusively occur in cancer cells.^15,16 This partially explains the observations indicating that whereas abrogation of survivin expression or functions triggers significant apoptosis of cancer cells, it has minimal effects on normal cells and tissues.^{17,18,19,20,21,22,23,24} Thus, survivin appears to be an ideal cancer preventive and therapeutic target.Targeting survivin for cancer treatment might cause little toxicity to normal tissues. Indeed, many natural chemopreventive and chemotherapeutic dietary components, such as resveratrol, silibinin, and sulindac²⁵ as well as selenium,²⁶ retinoid,^27,28 and vitamin D (eg, calcitriol)²⁹ down-regulate survivin expression in cancer cells. This is consistent with a role for survivin in oncogenesis. However, because of the lack of an appropriate in vivo animal model system, the role for survivin either in cancer-related or in other in vivo pathological processes¹¹ remains to be elucidated.Here, we report the generation of a novel transgenic mouse model that expresses the luciferase reporter gene as the human survivin gene surrogate under the control of a human survivin gene promoter. We demonstrated that this new mouse model possesses an active and highly responsive luciferase reporter system, which reflects the dynamic expression of endogenous survivin during pathology. We further show that survivin expression overlaps with several stem cell markers, which suggests that survivin may be a good stem cell marker as well. Our model has several unique features for in vivo imaging in comparison with the model previously reported.³⁰ In our model, we used the human survivin promoter with sufficient length (4.5 kb), instead of using a mouse survivin proximal promoter (0.8 kb; as a note, the design in Xia et al’s report³⁰ is good for studying the relationship between survivin expression and cell cycle/mitosis). Importantly, using the luciferase reporter as a surrogate to monitor survivin gene activity during various pathophysiological processes will increase sensitivity by several orders of magnitude in comparison with using GFP as a reporter for in vivo imaging, although GFP can provide strong signals. Therefore, with our model, it is now possible to monitor endogenous survivin gene activity through in vivo imaging of its surrogate luciferase activity during various pathophysiological processes. This mouse model has the potential to delineate the dynamic expression and role of survivin in cancer and other pathophysiological processes.     

血清肿瘤标志物在非小细胞肺癌骨转移中的诊断价值

目的:探肿瘤标志物在预测非小细胞肺癌(NSCLC)骨转移中的价值.方法:应用化学发光法检测98例NSCLC患者血清CEA、CYFRA21-1、CA19-9水平,同时对所有患者行全身骨扫描,以明确有无骨转移.结果:98例患者中40例临床诊断为NSCLC骨转移,出现骨转移的Ⅳ期患者,CEA、CYFRA21-1水平较Ⅲb前及无骨转移的Ⅳ期患者均明显升高;肿瘤标志物对于诊断NSCLC骨转移,CEA的灵敏度、特异度和准确度均较高,分别为80%、75.9%、77.6%,诊断性能最高.结论:肿瘤标志物具有NSCLC骨转移的辅助诊断价值,CEA诊断性能最高.     

Cerebellar Expression of Copper Chaperone for Superoxide,Cytosolic Cu/Zn-Superoxide Dismutase, 4-Hydroxy-2-Nonenal,Acrolein and Heat Shock Protein 32 in Patients with Menkes Kinky Hair Disease: Immunohistochemical Study

Background

To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death.

Methods

Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32).

Results

The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively.

Conclusion

In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.     

Safety and Efficacy of a Novel,Fenestrated Aortic Arch Stent Graft with a Preloaded Catheter for Supraaortic Arch Vessels: An Experimental Study in Swine

Thoracic endovascular aortic repair (TEVAR) shows limitations in cases in which the aortic pathology involves the aortic arch. The study aims were to test a fenestrated aortic arch stent graft (FASG) with a preloaded catheter for the supraaortic arch vessels and to perform a preclinical study in swine to evaluate the safety and efficacy of this device. Six FASGs with 1 preloaded catheter and 5 FASGs with 2 preloaded catheters were advanced through the iliac artery in 11 swines. The presence of endoleaks and the patency and deformity of the grafts were examined with computed tomography (CT) at 4 weeks postoperatively. A postmortem examination was performed at 8 weeks. The mean procedure time for the one and two FASG groups was 30.2 (27.9-34.5) min and 43.1 (39.2-53.7) min. The mean time for the selection of the carotid artery was 4.8 (4.2-5.5) min and 6.2 (4.6-9.4) min. Major adverse event was observed in one of 11 pigs. One pig died at 4 weeks likely because of the effects of the high dose of ketamine, while the remaining 10 pigs survived 8-week. For both the one and two FASG groups, no endoleaks, no disconnection, no occlusion of the stent grafts were observed in the CT findings and the postmortem gross findings. The procedure with the FASG could be performed safely in a relatively short procedure time and involved an easy technique. The FASG is found to be safe and convenient in this preclinical study with swine.

Graphical Abstract

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