The configuration of clinics and the use of biopsy and photography in oral premalignancy: a survey of consultants of the British Association of Oral and Maxillofacial Surgeons

Oral dysplastic lesions may have an increased chance of becoming oral squamous cell carcinoma, but to date their management remains controversial. The aim of this survey was to explore the current practical aspects of the management of patients with dysplasia by oral and maxillofacial consultants in the UK. In the survey we asked consultants about the numbers of patients they see with oral premalignant lesions, the frequency and specialty of designated hospital clinics, their use of photographs and biopsy, factors that influence their decision whether to biopsy a lesion at the first appointment, the procedure for treatment and follow-up and their use (if any) of chemopreventive agents. We found a wide variation in the practical aspects of managing patients with dysplasia, and the lack of consistency among clinicians supports the idea of an initiative to establish more robust national guidelines to use as a gold standard in the future.     

Risk of cancer in patients with chronic pouchitis after restorative proctocolectomy for ulcerative colitis

Aim The aim of this study was to evaluate the consequences of chronic pouchitis after restorative proctocolectomy for ulcerative colitis. Method Forty‐two patients with chronic pouchitis underwent pouch endoscopy with biopsies after a median of 8.3 years of postoperative follow up. The pouchitis disease activity index (PDAI) was calculated. Morphological changes were recorded. Immunohistochemical analyses for cyclooxygenase 2 (COX‐2), Ki‐67 and p53 were performed, as was DNA flow cytometry. Endoscopy was also carried out in 10 patients without pouchitis and in nine healthy subjects. Results In patients with chronic pouchitis, the PDAI was 6 (standard error of the mean ± 4). Eighteen (43%) patients used continuous medication. The PDAI correlated positively with villous atrophy (P < 0.05). None of the pouch biopsies showed dysplasia. COX‐2 immunostaining was detected in 35 (83.3%) patients with chronic pouchitis, in five (50%) without pouchitis, but in none of the normal controls. COX‐2 expression correlated with mucosal atrophy (P < 0.01). In 15 (35.7%) of 42 patients with chronic pouchitis, Ki‐67 immunostaining was increased, but no increase was observed in either control group (P < 0.002). No p53 immunopositivity was found, and DNA flow cytometry was normal in all pouches. One of the patients developed adenocarcinoma at the anal anastomosis. Conclusion No dysplastic changes were detected during the first decade after surgery. Routine follow up of patients with chronic pouchitis with a hand‐sewn anastomosis may not be necessary, although a small risk of cancer seems to remain at the anal anastomosis. The follow up should be focused on at‐risk groups.     

Catheter ablation of stable and unstable ventricular tachycardias in patients with arrhythmogenic right ventricular dysplasia

INTRODUCTION: A reentrant circuit within an area of abnormal myocardium is suspected as the origin of ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular dysplasia (ARVD). OBJECTIVES: To examine the relationship between the reentrant circuits of VT and the abnormal electrograms in ARVD, and to assess the feasibility of a block line formation in the reentrant circuit isthmus utilizing electroanatomical mapping system (CARTO) guidance. METHODS AND RESULTS: An electrophysiological study and catheter ablation (CA) were performed in 17 ARVD patients (13 men, 47 +/- 17 year) using CARTO. Endocardial mapping during sinus rhythm demonstrated electrogram abnormalities extended from the tricuspid annulus (TA) or the right ventricular outflow tract in 16 of 17 patients. In 13 hemodynamically stable VTs, the reentrant circuits and critical slow conduction sites for the CA were investigated during VTs. The entire macro-reentrant pathway was identified in 6/13 stable VTs (figure-of-8 in 4, single loop in 2). In the remaining seven VTs, a focal activation pattern was found in four and an unidentifiable pattern in three. CA successfully abolished all the macro-reentrant and focal tachycardias, however, not effective in three unidentifiable VTs. In the 13 cases with unstable VT, the linear conduction block zone was produced between the sites with abnormal electrograms and the TA. Ultimately, 23/26 VTs (88%) became noninducible after the CA. During follow-up (26 +/- 15 months), 13/17 patients remained free from any VT episodes. CONCLUSIONS: CARTO is useful for characterizing the anatomical and electrophysiological substrates, and for identifying the optimal ablation sites for VT associated with ARVD.     

两个新RUNX2基因突变引起家族性锁骨颅骨发育不全

目的 探讨RUNX2基因突变在锁骨颅骨发育不全病因研究中的意义及两个中国家族性锁骨颅骨发育不全家系发病的分子机制.方法 提取收集到的2个锁骨颅骨发育不全家系中4例患者和4名家系健康成员、102名无关正常对照外周血基因组DNA,应用PCR扩增产物双向直接测序方法 检测RUNX2基因第1～7外显子及相邻侧翼区的DNA序列,测序结果 与RUNX2基因正常序列对比分析.对发现的突变位点用酶切方法 证实.结果 测序结果 发现一家系中两例父子患者的RUNX2基因第1外显子发生错义突变c.346T＞A(W116R),该错义突变通过Bsr Ⅰ限制性内切酶对PCR扩增产物行酶切分析得到进一步确认.另一家系中两例患者的RUNX2基因第3外显子发生无义突变c.610A＞T(K204X).在两个家系中的正常家系成员和无关正常对照RUNX2基因DNA序列中没有发现上述突变.结论 通过RUNX2基因,检测在中国人群中发现两个RUNX2基因新致病突变,扩展了遗传性锁骨颅骨发育不全的基因突变谱,对阐明该病发病机制及其基因诊断和遗传咨询有重要意义.     

SEDL基因及其突变体真核表达载体的构建与鉴定

目的构建SEDL基因及其突变体与增强型绿色荧光蛋白(EGFP)表达载体的融合表达质粒pEGFP-C3-SEDL并获得表达。方法分别提取X连锁迟发性脊柱骨骺发育不良(SEDT)患者和正常对照外周血淋巴细胞RNA,RT-PCR方法扩增SEDL基因cDNA,双酶切后克隆至pEGFP-C3空载体,构建表达质粒pEGFP-C3-SEDL。双酶切和DNA测序鉴定后,转染COS-7细胞,通过流式细胞仪和荧光显微镜观察重组蛋白表达情况。结果 DNA测序显示重组真核表达载体pEGFP-C3-SEDL构建成功,SEDL基因c.370-371ins A突变位点被成功克隆到突变体重组质粒中。荧光倒置显微镜观察证实重组质粒均能在细胞内进行蛋白表达。结论 SEDL基因及其突变体真核表达载体的成功构建为其进一步研究SEDL基因突变致SEDT的分子机制奠定了基础。     

先天性缺指（趾）-外胚层发育不良-唇/腭裂综合征的临床研究

目的探讨先天缺指（趾）-外胚层发育不良-唇/腭裂综合征的临床表现,诊断标准,遗传学特点及治疗措施。方法 2008年3月至2009年9月收集先天缺指（趾）-外胚层发育不良-唇/腭裂综合征女性患者一例,针对上唇缺损行手术修补,对其进行家系问卷和DNA检查,观察患者的临床表型和发病特点,分析可能的遗传方式。结果术后患者伤口愈合良好,无并发症发生,此例患者随访半年,术后明显改善了患者的外观,研究收集的这个典型病例未追溯到明显家族遗传史。结论收集的一个患者属典型的散发病例,通过对该患者的诊疗,证明治疗应是多学科的,主要是针对外观进行整形外科手术,临床的早期检查和正确诊断对后期治疗具有重要意义。产前诊断意义尤为重大。     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

BNP concentrations and cardiovascular adaptation in preterm and fullterm newborn infants

To evaluate and compare cardiovascular adaptation of 36 preterm and 34 fullterm newborns, we analyzed BNP concentration and echocardiographic parameters at day 3 of life and at day 28 (± 2). On day 3 BNP concentrations (pg/ml) resulted higher in PDA preterm group (n = 11; 125, IQR 56.1-301) than preterm without PDA (n = 25; 25.5 IQR 10.9-49; p < 0.001) than fullterms (n = 34; 55.1 IQR 23.6-82.7; p = 0.013). No difference resulted in all groups at 28 days (respectively: 12.7 IQR 4.9-23.8; 15.6 IQR 10-22; 8.9 IQR 5.6-20.6). Because of the newborns' growth, all echocardiographic parameters increased with linear relationship with body weight. On day 3 BNP concentration and echocardiographic parameters were not correlated besides LA/AO in preterms with PDA (p = 0.0015). On day 28, BNP was significantly correlated with mVTI (p = 0.019), M (p = 0.007) and LA (p = 0.005) in fullterms and only with LA (p = 0.007) in preterms.In conclusion, BNP concentrations and echocardiographic measures confirm that preterm, and fullterm newborns conduct themselves in a similar manner during the transition from foetal to post-natal circulation, reaching low levels at a month of life. The presence of PDA during first days of life has no significant impact in this adaptation. LA is the echocardiographic parameter mostly related to BNP concentration in the newborns.