The Evolution of Nonimmune Histological Injury and Its Clinical Relevance in Adult-Sized Kidney Grafts in Pediatric Recipients

To describe the evolution, risk factors and impact of nonimmune histological injury after pediatric kidney transplantation, we analyzed 245 renal allograft protocol biopsies taken regularly from the time of transplantation to 2 years thereafter in 81 consecutive rejection-free pediatric recipients of an adult-sized kidney. Isometric tubular vacuolization was present early after transplantation was not progressive, and was associated with higher tacrolimus pre-dose trough levels. Chronic tubulo-interstitial damage and tubular microcalcifications were already noted at 3 months, were progressive and had a greater association with small recipient size, male donor gender, higher donor age and female recipient gender, but not with tacrolimus exposure. Renal function assessment showed that older recipients had a significant increase in absolute glomerular filtration rate with time after transplantation, which differed from small recipients who showed no increase. It is concluded that progressive, functionally relevant, nonimmune injury is detected early after adult-sized kidney transplantation in pediatric recipients. Renal graft ischemia associated with the donor-recipient size discrepancy appears to be a greater risk factor for this chronic histological injury, suggesting that the exploration of additional therapeutic approaches to increase allograft perfusion could further extend the graft survival benefit of adult-sized kidneys transplanted into small children.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

Y染色体微缺失不育患者精液细胞学观察

目的:对Y染色体AZF区域微缺失不育患者进行精液细胞学检查,从而评估其生精功能。方法:收集35例AZF缺失不育患者,年龄23~44岁,经3次以上精液常规分析证实,26例为非梗阻性无精子症,9例为严重少精子症。按照AZF缺失部位分为以下4组进行观察:AZFa+b+c区域缺失组5例,AZFb+c缺失(4例)及单独AZFb缺失(3例)组7例,AZFc缺失组23例。采集患者精液,待自然液化后离心,生理盐水洗涤2次,离心沉淀物经生理盐水稀释后涂于干净玻片上,瑞吉染色,光学显微镜下观察。对其中6例患者进行了睾丸组织病理学检查。结果:AZFa+b+c缺失组,精液细胞学检查均未见各级生精细胞,可见少量上皮细胞。其中1例经睾丸活组织病理学检查,生精小管中未见各级生精细胞,为唯支持细胞综合征,与精液细胞学检查结果一致。AZFb+c缺失及单独AZFb缺失组,精液细胞学检查其中6例细胞停滞在精母细胞阶段,2例睾丸活检见生精阻滞在初级精母细胞阶段。1例AZFb缺失的患者精液细胞学检查见初级精母细胞、次级精母细胞和精子细胞,但睾丸活检显示阻滞在精母细胞阶段。AZFc缺失组中,少精子症组(8例)患者生精细胞检查5例停滞在精母细胞阶段,见少量精子细胞,另3例未见各级生精细胞;无精子症组(15例)患者未见各级生精细胞,其中2例经睾丸活检,证实为唯支持细胞综合征。结论:精液细胞学检查对AZF缺失患者能有效评估生精功能,作为一项无创检查技术,容易被患者接受,推荐作为临床评估生精功能的一项方法。     

累及移行带前列腺癌的诊断分析

目的分析累及移行带前列腺癌的临床特征,提高移行带前列腺癌的诊断率。方法回顾我院收治的77例前列腺癌患者,一组44例仅限于外周带;另一组33例已累及移行带。分析两组的临床表现、直肠指检、移行指数、前列腺移行带特异性抗原密度、前列腺特异性抗原、经直肠前列腺超声以及前列腺穿刺活检。结果两组患者的年龄、排尿期和储尿期症状、直肠指检阳性率、移行指数、前列腺移行带特异性抗原密度、前列腺特异性抗原以及病理分级没有显著性差异。移行带肿瘤存在泌尿系转移的风险。经直肠超声为移行带可疑病灶的定位提供了重要的参考,而对可疑病灶穿刺活检则能提高累及移行带前列腺癌的诊断率。结论经直肠超声行移行带可疑病灶的穿刺活检是诊断累及移行带前列腺癌的有效手段。     

152例肝移植术后肝功能异常的肝活检

目的评价肝活检在明确肝移植术后肝损害病因中的作用，分析组织学诊断存在误差的常见原因，进一步提高肝活检的准确性，以利临床治疗。方法260例肝活检来自于152例肝移植受者，术后出现临床无法解释的肝功能异常，肝功能检测结果高于正常值的2倍以上。回顾组织学改变及最终的临床诊断，评价相符程度。结果大部分的组织学诊断与最终的临床诊断相符，有7例组织学改变为胆管炎后经进一步临床检查证实4例为血管并发症、2例为败血症、1例为保存性损伤。2例组织学诊断为保存性损伤的病例后证实为药物性肝损害。结论移植后肝活检可明确许多肝功能异常的原因；评判病变的严重程度，指导临床治疗；对一些复杂病例应将以往的活检和整个临床病程、其他实验室检查及影像学检查进行综合考虑，可提高诊断的准确性。     

骨肿瘤经皮套管针穿刺活检

[目的]报告171例穿刺活检的结果并探讨相关影响因素。[方法]采用套管活检针对骨肿瘤进行术前穿刺活检，回顾分析171例骨肿瘤患者的穿刺活检的结果。[结果]171例，穿刺活检阳性155例，穿刺活检阳性率90．64％，行手术治疗获得大体标本病理诊断者122例，活检准确诊断者98例，准确率80．33％，误诊5例。恶性肿瘤总例数110例，穿刺活检敏感性95．41％，特异性100％。[结论]穿刺活检对骨肿瘤术前诊断有较大价值，实施者对骨肿瘤的认识水平，操作的细致程度，对活检阳性率、准确率及并发症的发生有重要影响。     

术中淋巴染色对早期乳腺癌前哨淋巴结判定作用的研究

目的：探讨术中淋巴染色在早期乳腺癌前哨淋巴结判定中的作用。方法：62例Ⅰ、Ⅱ期乳腺癌，术中向乳腺肿块或其周围组织内注入1％亚甲蓝注射液4ml，术后将腋淋巴结按部位统计每例染色淋巴结的数量、转移度，计算用染色淋巴结判断腋淋巴结转移情况的敏感性、特异性、准确性和漏诊率。结果：62例淋巴染色均而获成功。23例腋淋巴结查见转移癌，其中20例染色淋巴结查见转移癌。判断腋淋巴结有无转移敏感性为87．0％（20／23），特异性为100％（39／39），准确性为93．7％（59／62），漏诊率为13．0％。染色淋巴结的转移度34．8％（39／112），与总体淋巴结及未染色淋巴结的转移度（27．5％、29．7％）差异没有统计学意义。结论：采用亚甲蓝作为术中淋巴染色剂，对早期乳腺癌病人有较高的成功率，应用染色淋巴结作为前哨淋巴结来判断腋淋巴结转移情况有较高的漏诊率，其应用价值尚待进一步大样本的研究评价。     

Age estimation in biopsy specimens of dentin

Determination of age at death on the basis of aspartic acid racemization in dentin is one of the most reproducible and accurate methods. In Germany, age estimation by this method has so far generally not been applied to living persons, since the extraction of a tooth exclusively for age estimation when it is not medically indicated is regarded as ethically and legally problematic. The development of a biopsy technique applicable to dentin took place against this background. Testing the technique and analysis of dentinal biopsy specimens revealed that the biopsy technique is a low-risk procedure that causes only minor discomfort to the affected person. It is readily practicable and facilitates standardized specimen removal. The relationship between the extent of aspartic acid racemization in dentinal biopsy specimens and age is very close, facilitating age estimation. A prerequisite for accurate results is the performance of biopsies under strictly standardized conditions. If this is guaranteed, age determination on the basis of aspartic acid racemization in dentinal biopsy specimens appears to be superior in precision to most other methods in living persons and can be used for all age groups.     

Proximal myotonic myopathy

Three Swedish patients with proximal muscle weakness, myotonia and lack of CTG expansion on genetical analysis are presented. Clinical neurological and neurophysiological examination and muscle biopsy were performed. There was an indication of autosomal dominant inheritance in 2 of the 3 patients. The main symptoms and clinical findings in the 3 patients were weakness of the proximal muscles, myotonia, muscle stiffness, muscle pain and muscle atrophy. Neurophysiological examination showed myotonic bursts and muscle biopsy snowed a variation of fibre sizes, an increased number of muscle fibres with centralized nuclei and scattered atrophic muscle fibres. Laboratory data showed elevated CK, GT and LD in 1 patient. Before genetical analysis was performed, all 3 patients had been diagnosed as atypical cases of myotonic dystrophy. However, the symptoms, clinical signs, laboratory data, electrophysiological and muscle biopsy findings were compatible with proximal myotonic myopathy (PROMM).