Molecular and morphological analysis of adenoid cystic carcinoma of the breast with synchronous tubular adenosis

Adenoid cystic carcinoma (ACC) of the breast is a rare tumour. Its recognition as a special type of breast carcinoma is very important because its prognosis is better than the not-otherwise-specified invasive ductal carcinoma and its treatment may not include axillary dissection. Tubular adenosis (TA) is a very rare condition of the breast that is histologically benign; however, it has been described in association with invasive ductal carcinoma. There are scant data regarding the molecular genomic alterations in ACC of the breast and no data has been presented on TA. Herein, we provide a morphological characterisation of TA arising synchronically with ACC in the breast. To characterise these lesions, we performed ultrastructural analysis, three-dimensional reconstruction and molecular analysis using immunohistochemistry and comparative genomic hybridisation. The copy number alterations found in ACC were restricted to small deletions on 16p and 17q only, whereas the TA harboured gains on 1q, 5p, 8q, 10q, 11p and 11q and losses on 1p, 10q, 11q, 12q, 14q, 15q and 16q. These molecular data highlight the genomic instability of TA, a benign florid proliferation intermingled with ACC, and do not provide evidence of molecular evolution from TA to ACC.     

Functional results of angular-stable plate fixation in displaced proximal humeral fractures

INTRODUCTION: The availability of angular-stable plate/screw systems led to a euphoric use of these implants for the treatment of displaced proximal humerus fractures. The high implant costs seem to be justified by a potentially improved outcome. PATIENTS AND METHODS: Thirty one patients (20 female, 11 male, mean age: 62+/-16 years) with two-, three- and four-part proximal humerus fractures (Neer classification) were operated using the proximal humeral internal locking system (PHILOS). The mean follow-up time was 19+/-3 postoperative months (range: 340-720 days). Functional results (Constant score, UCLA-score) were analysed and compared to an equivalent historic control group of 60 patients operated for the same fracture types using two one-third tubular plates. Additionally, total implant costs for each technique were compared. RESULTS: Complications in the PHILOS group included one implant failure with refracture, one secondary dislocation, two cases of subacromial impingement, and two cases of partial avascular necrosis of the humeral head. The mean Constant score (age- and sex-matched) was 80+/-11% for the affected side and 104+/-13% for the healthy side. The UCLA scores were excellent in 10%, good in 67%, and fair in 23% of the patients. Complication rate and functional results did not differ significantly from the control group treated with one-third tubular plates. Implant costs were significantly higher for the PHILOS group (684+/-40 Euro vs. 158+/-20 Euro, p<0.05). CONCLUSION: Our study showed similar functional results using either plate. Although the PHILOS plate may provide important advantages in specific situations, such as osteoporotic bone, its use as a standard must be carefully judged under the economic aspect of the significant higher implant costs.     

Recurrent nephrolithiasis in renal tubular acidosis. Metabolic profiles,therapy and course

13 patients with recurrent urolithiasis and distal renal tubular acidosis (RTA I) were investigated for lithogenic metabolic disorders. Treatment was given and the patients observed for periods of up to 10 years.     

自身免疫病所致肾小管性酸中毒(RTA)——14例报告和分析

为了进一步探讨自身免疫病与RTA之间的关系,本文报告14例自身免疫病所致RTA,均为I型,其中完全性者2例,不完全性者12例。并结合文献复习对其临床特点、发病机理进行了讨论。认为自身免疫病是继发性RIA的常见病因;对自身免疫病进行尿PH测定和血气分析筛选,必要时行氯化铵负荷试验有助于RTA的早期诊断;免疫性因素在其发病过程中可能起主导作用,某些非免疫性因素也参与发病;RTA的预后取决于原发病。     

Nonlinearities in amoxycillin pharmacokinetics. I. Disposition studies in the rat.

Several features of amoxycillin pharmacokinetics in man are not well known in spite of the extensive clinical use of the antibiotic. In this paper it is demonstrated that amoxycillin disposition kinetics in rats is clearly nonlinear, and that this may be due mainly to its elimination mechanisms. At different intravenous bolus dose levels, and in steady-state perfusion studies, the most striking feature is an increased renal clearance as dose increases (from 3.5 to 7.0 mg kg-1 for intravenous bolus, and from 4.6 to 20.0 micrograms min-1 for intravenous perfusions). This phenomenon has been attributed to a saturation of the active renal tubular reabsorption of the antibiotic. When the intravenous dose is substantially increased (28.0 mg kg-1 bolus), plasma clearance tends to stabilize, probably because saturation of the active tubular secretion of amoxycillin takes place at these doses. Extrarenal clearance seems to remain linear throughout the entire dose range. On the basis of these observations and a review of selected bibliography, an interpretation of the kinetic disposition behaviour of amoxycillin in man is attempted.     

On a dominantly inherited myopathy with tubular aggregates

A 19-year-old patient presented with exercise-related myalgia, fatigue and elevated creatine kinase levels. Histology of a muscle biopsy was characterized by the presence of very large amounts of tubular aggregates. Both his father and paternal grandfather had elevated creatine kinase and large amounts of tubular aggregates in their muscle biopsies. The aggregates consisted of closely packed vesicles and tubules filled with electron-dense material or with one to several smaller tubules. Disorders with tubular aggregates in the muscle fibres such as hyperornithinaemia with gyrate atrophy of the retina, hypokalaemic periodic paralysis, hyperkalaemic periodic paralysis, myotonia congenita, alcoholism, osteomalacic myopathy etc. have been excluded. Tubular aggregates can be found in muscle disorders characterized by exercise-induced cramps, pain and stiffness. They also represent the predominant histological feature of some familial myopathies due to a yet unidentified genetic defect. In our family, there was male-to-male transmission, confirming dominant inheritance.     

Epithelial–mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis

Tubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker α-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered α-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans.     

高脂蛋白（a）的冠心病患者内皮祖细胞功能受损

目的比较高脂蛋白(a)[Lp(a)]的冠心病患者和低Lp(a)的冠心病患者内皮祖细胞(EPC)的功能差异。方法酶联免疫法测定Lp(a),差速贴壁法分离EPC,Dil-ac-LDL吞噬及lectin结合鉴定EPC并计数。MTT法检测EPC存活与增殖,改良Boyden小室检测细胞迁移,明胶玻片法检测细胞黏附,杂交瘤皿上观察并计数单个细胞克隆数,基质胶上测量管状结构形成长度。结果高Lp(a)的冠心病患者循环EPC数显著低于低Lp(a)的冠心病患者(109.4±13.8个/视野比384.0±37.0个/视野,P=0.0023);MTT分析显示,低Lp(a)组OD值为0.77±0.05,而高Lp(a)组OD值为0.23±0.04(P=0.0018),表明高Lp(a)的冠心病患者EPC的生存状态较差,这一点在凋亡检测中进一步得到体现,高Lp(a)组EPC凋亡率显著高于低Lp(a)组(14.9%±3.3%比4.1%±0.8%,P=0.035)。与低Lp(a)组比较,高Lp(a)组EPC的黏附(25.3±4.6个/视野比78.6±6.8个/视野,P=0.0030)、迁移(22.0±2.6个/视野比56.0±4.9个/视野,P=0.0037)、克隆形成(2.4±0.4个/视野比11.0±1.3个/视野,P=0.0003)、管状结构形成(7.4±1.2 mm/field比33.3±2.6 mm/field,P=0.0001)均显著受损。结论与低Lp(a)的冠心病患者相比,高Lp(a)的冠心病患者EPC功能受损更严重。     

Ampullary Adenoma Treated by Endoscopic Double-Snare Retracting Papillectomy

We report herein improved methods for the safe and successful completion of endoscopic papillectomy (EP). Between January 2008 and November 2011, 12 patients underwent double-snare retracting papillectomy for the treatment of lesions of the major duodenal papilla. The main outcomes were en bloc resection rates, pathological findings, and adverse events. All of the patients (mean age, 60.1 years; range, 38 to 80 years) were diagnosed with ampullary adenoma by endoscopic forceps biopsies prior to endoscopic snare papillectomy. En bloc resection by double-snare retracting papillectomy was successfully performed for all lesions (median size, 12.3 mm), comprising six tubular adenomas, one tubulovillous adenoma, three cases of epithelial atypia, one hamartomatous polyp, and one case of duodenitis with regenerative change. Significant hemorrhage and pancreatitis were observed in one case after EP. Adenoma recurrence occurred in three patients during follow-up (median, 28.5 months) at a mean interval of 2 months postoperatively (range, 1 to 3 months). No serious adverse events were observed. Double-snare retracting papillectomy is effective and feasible for treating lesions of the major duodenal papilla. Further treatment experience, including a single-arm phase II study, needs to be accumulated before conducting a randomized controlled study.