前列腺上皮内瘤变的基因微阵列分析

目的:通过基因微阵列分析,研究经显微切割后的前列腺上皮内瘤变(PIN)的基因表达谱,并将其与前列腺良性增生(BPH)及前列腺癌的mRNA基因表达谱进行对比,探讨前列腺癌的发生、发展,检测PIN及前列腺癌的肿瘤标志物。方法:采用美国Affymetrix公司的HG-U133A基因芯片,检测了16例人的前列腺组织标本,包括5例良性标本,6例PIN以及5例前列腺癌标本,均为新鲜冰冻组织。为了精确获得上皮细胞基因表达谱,避免周围间质细胞及单核细胞的RNA 对结果的影响,我们采用了激光捕获显微切割技术,分别得到了3组纯的上皮细胞群进行研究。结果:有些基因的表达强度在从良性增生到PIN到癌的转化过程中,呈逐渐改变的趋势,但笔者发现3组间基因表达谱存在非常显著的差异。与BPH及前列腺癌相比,PIN有其独特的基因表达谱。结论:基因表达谱中显著上调及下调的特异性基因,可以将PIN 和BPH及前列腺癌中区分开来;基因微阵列分析也有助于揭示代谢通路及信号转导途径的变化,有利于靶基因治疗。     

Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy.

Complications in a donor are a distressing but inevitable occurrence, since graft procurement is a major undertaking. Although the technique for procurement has some similarities to hepatic resection, a donor is very unlike a patient with malignancy. The risk factors identified in these patients cannot be extrapolated to donors. Donor hepatectomy carried out from June 1995 to March 2005 in Chang Gung Memorial Hospital, Kaohsiung Medical Center was reviewed with the aim of identifying risk factors for complications. There were 204 living donor liver transplants, with 205 donor hepatectomies, as 1 living donor liver transplantation was a dual graft. Ten donors (4.88%) suffered complications. There was no difference in terms of age, gender, body weight, operation, and parenchymal time between those who had complications and those who did not. There was also no difference in liver function tests between the 2 groups of donors, but the total bilirubin was significantly higher in donors with complications. The graft weight and remnant liver volume were also similar. The proportion of donors with fatty liver was the same between the 2 groups. The mean blood loss in donors with complications was 170 +/- 79 mL, and that for donors without complications was 95 +/- 77 mL. There was a statistically significant greater blood loss in donors with complications (P < 0.05). The number of segments removed in donors with complications was also higher compared to donors without complications (P < 0.03). Using multivariate analysis, intraoperative blood loss and the number of segments removed were found to be independent risk factors for donor complications. Intraoperative blood loss during graft procurement must be kept low to minimize complications in donors.     

全肺切除术治疗肺癌的临床分析

目的 :探讨全肺切除术和经心包内处理血管的全肺切除术治疗肺癌的效果。方法 :对 74例Ⅱb～Ⅲb期肺癌患者行全肺切除术 ,其中 32例在肺癌的全肺切除术中进行了心包内处理血管 ,其余 4 2例行标准全肺切除术。结果 :心包内处理血管组与标准切除组术后各有 1例并发脓胸 ,其中心包内处理血管组的并发脓胸者死亡。术后两组分别随访 2 2例和 31例 ,5年生存率分别为 18.1%和 16 .1%。经心包内处理血管的全肺切除与标准全肺切除术患者 5年生存率和术后并发症发生率差异均无显著性 (P =1.0 0 0和P >0 .0 5 )。结论 :全肺切除术中力争达到根治 ,经心包内处理血管技术的应用 ,对于提高患者的生存率、改善晚期肺癌的生活质量是有价值的     

红藻氨酸作用后海马神经元胞膜表面的超微结构的原子力显微镜观察

目的 观察原代培养神经元在红藻氨酸(KA)作用下细胞表面形态的三维构像变化。方法 利用原子力显微镜(AFM)对大鼠海马神经元经不同浓度的KA(25和250μmol／L，50和100nmol／L)分别作用10min和100min后的表面结构进行纳米级水平扫描和观测。结果 正常海马神经元表面光滑，起伏均匀、规律；KA作用后神经元呈退行性改变，表现为胞体肿胀，胞膜表面粗糙，出现隆起和“孔洞”样结构，并且其变化程度分别与作用时问和KA浓度呈量-效关系。结论 KA对海马神经元毒性作用后胞膜表面超微结构所产生的明显变化，可借助AFM清晰观察，并定量分析。     

Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human kidney disease and is caused by germline mutations in PKD1 (85%) or PKD2 (15%). It has been estimated that around 1% of tubular cells give rise to cysts, and cell hyperproliferation has been noted to be a cardinal feature of cystic epithelium. Nevertheless, it is uncertain whether the increase in proliferative index observed is an early or late feature of the cystic ADPKD kidney. METHODS: Two Pkd2 mouse mutants (WS25 and WS183) have been recently generated as orthologous models of PKD2. To determine the effect of Pkd2 dosage on cell proliferation, cyst formation and renal fibrosis, we studied renal tissue from Pkd2(WS25/WS25) and Pkd2(+/-) mice by histological analysis. We also examined the proliferative index in archival nephrectomy tissue obtained from patients with ADPKD and normal controls. RESULTS: The proliferative index of non-cystic tubules in Pkd2 mutant mice as assessed by proliferating cell nuclear antigen and Ki67-positive nuclei was between 1-2%, values 5-10 times higher than control tissue. Similarly, the proliferative index of non-cystic tubules in human ADPKD kidneys was 40 times higher than corresponding controls. In Pkd2 mutant mice, significant correlations were found between the fibrosis score and the mean cyst area as well as with the proliferative index. Of significance, proliferating tubular cells were uniformly positive for polycystin-2 expression in Pkd2(+/-) kidney. CONCLUSION: These results suggest that an increase in cell proliferation is an early event preceding cyst formation and can result from haploinsufficiency at Pkd2. The possible pathogenic link between tubular cell proliferation, interstitial fibrosis and cyst formation is discussed.     

The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.     

两个跳槽者的内心独白

医疗人才的竞争已经形成。医疗人才由著名大医院流向中外合资合作医疗机构的局面已经出现。这是一个开放的时代。每个人都有选择自己职业、生活的权利。     

Nitric oxide production and immunoglobulin deposition in leptospiral hemorrhagic respiratory failure.

Diffuse pulmonary hemorrhage leading to death is a syndrome which may develop in leptospirosis, but its pathophysiology is not well documented. We report an autopsy case of leptospirosis. A healthy 41-year-old man presented with low back myalgia, dry cough and fever for 4 days and a normal chest X-ray on admission. Acute respiratory failure developed hours later. Profuse bloody fluid appeared in the endotracheal tube immediately after intubation. Chest X-ray showed whiteness across all lung fields. He died of persistent shock 16 h after the onset of acute respiratory failure. Autopsy revealed diffuse pulmonary hemorrhage with hyaline-membrane formation, myocarditis, interstitial nephritis and hepatitis. Silver stain of lung and kidney tissue demonstrated leptospires. Immunohistochemical staining showed inducible nitric oxide synthase in alveolar macrophages. Immunofluorescein staining showed immunoglobulin in alveolar septum and alveolar space. This case suggests that hemorrhagic diffuse alveolar damage with persistent shock is related to over-production of nitric oxide and immunoglobulin deposition in fatal leptospirosis.     

重组骨形态发生蛋白-2结合软骨下钻孔治疗犬关节软骨全层缺损的实验研究

目的 研究重组骨形态发生蛋白-2(rhBMP-2)结合软骨下骨钻孔治疗犬关节软骨全层缺损的可行性，为临床应用提供实验依据。方法 依照软骨缺损处理方法的不同将64侧股骨髁随机均分为4组：①结合组：软骨下骨钻孔 胶原海绵吸附rhBMP-2充填软骨缺损；②BMP组：胶原海绵吸附rhBMP-2充填软骨缺损；③钻孔组：单纯软骨下骨钻孔；④对照组：不作处理或单纯用胶原海绵填塞。术后2、4、8、12周取材观察其大体、光镜、透射电镜、免疫组织化学情况。结果 除对照组仅有纤维组织修复外，其余3组均有不同程度的软骨修复，但结合组的修复在组织细胞形态、超微结构、Ⅱ型胶原含量等方面均明显优于其他两组。结论rhBMP-2结合软骨下骨钻孔能有效修复犬膝关节软骨的全层缺损，该技术可行，有望在临床应用。     

组织工程支架在犬急性脊髓损伤修复中应用的初步研究

目的探讨携带神经干细胞的聚碳酸亚丙酯[poly（propylene carbonate），PPC]可降解支架移植在犬脊髓急性损伤后修复中的作用。方法制作犬T13脊髓左侧半切损伤模型。将实验动物随机分为3组：细胞支架组在损伤后1周时将填充神经干细胞的PPC可降解支架植入损伤区．支架组只植入支架，对照组不作移植。8周后观察支架的组织反应、降解情况及神经干细胞的迁移分化和脊髓轴突再生情况。结果支架部分降解，管腔内未见瘢痕侵入。神经干细胞向支架邻近部位广泛迁移、扩散，并分化为3种神经细胞表型。神经丝蛋白（NF）及髓鞘碱性磷酯蛋白（MBP）免疫组化显示细胞支架组脊髓损伤区邻近部位的继发损害较其他组轻。结论携带神经干细胞的PPC可降解支架在犬脊髓组织中无明显组织反应．能够抵御瘢痕侵入：其携带的神经干细胞能够整合入邻近脊髓组织并起到一定保护作用。