Tricuspid Valve Replacement in Rheumatic Heart Disease

The diagnosis of tricuspid valve disease is often difficult; the best treatment is not yet established. Twenty patients had tricuspid valve replacements at St. Thomas''s Hospital as part of multiple valve replacement procedures. The hospital mortality was 25%, most deaths being due to a low cardiac output causing hepatorenal failure. Preoperative cardiac cachexia had a fatal outcome in all cases. Except in two instances, surviving patients returned to a satisfactory level of activity.     

Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve Surgery for Aortic Stenosis

Background

The prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting.

Methods

This was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography.

Results

At baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (p<0.001), pulmonary hypertension (p = 0.003), more dilated RVs (p = 0.001), and more frequent RV dysfunction (p = 0.001). Patients were followed for an average of 5.2 (±2.8 SD) years. By multivariable Cox regression analysis TR (p = 0.014), RV dysfunction (p = 0.046), age (p = 0.001) and concomitant coronary artery bypass graft surgery (CABG, p = 0.003) were independently associated with overall mortality. By Kaplan-Meier analysis, survival rates were significantly worse in patients with significant than with non-significant TR (log rank p = 0.001).

Conclusions

TR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients.     

Analysis of Extracellular Superoxide Dismutase and Akt in Ascending Aortic Aneurysm With Tricuspid or Bicuspid Aortic Valve

Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of extracellular superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9). The results showed a significant reduction of SOD3, phospho-Akt and Akt protein levels in AsAA tissues from patients with BAV, compared to controls, whereas the differences observed between controls and patients with TAV were not significant. The decreased levels of SOD3 and Akt in BAV aortic tissues are associated with decreased Erk1/Erk2 phosphorylation and MMP-9 levels increase. The authors suggest a role of decreased SOD3 protein levels in the progression of AsAA with BAV and a link between ECM modifications of aortic media layer and impaired Erk1/Erk2 and Akt signaling in the late stages of the aortopathy associated with BAV.Key words: Ascending aortic aneurysm, bicuspid aortic valve, medial degeneration, smooth muscle cells, extracellular superoxide dismutase, Akt, tri-cuspid aortic valve     

不同三尖瓣成形术治疗风湿性二尖瓣病变合并三尖瓣关闭不全临床研究

目的:比较行不同成形术治疗风湿性二尖瓣病变合并功能性三尖瓣关闭不全的外科疗效。方法:选取风湿性二尖瓣病变合并功能性三尖瓣关闭不全患者119例,按照治疗方法将患者分为对照组、三尖瓣人工环植入成形术组(成形环组)以及三尖瓣缝线成形术(缝线组),分别统计患者年龄、性别、手术方式、术前及术后心功能分级等指标,采用t检验对患者术前、术后2周以及术后6个月心脏各腔内径进行统计学分析。结果:患者行三尖瓣人工环植入成形术以及三尖瓣缝线成形术治疗后,心脏各腔内径均明显缩小,成形环组患者术后心脏内径缩小最显著,行三尖瓣缝线成形术患者次之。术前成形环组左心房、右心房以及右心室内径较对照组扩大明显(P0.05);术前缝线组左心房、右心房以及右心室内径较对照组扩大明显(P0.05);术前成形环组与缝线组右心房、右心室内径组间无明显差异;术后2周以及术后6个月三组间左心房内径无明显差异(P0.05)。术后2周成形环组以及缝线组右心房以及右心室内径仍大于对照组(P0.05),术前成形环组与缝线组组间无显著差异。术后6个月成形环组右心房以及右心室内径较缝线组显著缩小(P0.05),成形环组和对照组间无明显差异。结论:治疗风湿性二尖瓣病变合并功能性三尖瓣关闭不全的方法中,三尖瓣人工环植入成形术效果优于三尖瓣缝线环缩术。     

Successful Ablation of Cavotricuspid Isthmus-dependent Atrial Flutter Guided by Contact Force Vector in a Patient After a Tricuspid Valve Replacement

A 46-year-old man after a tricuspid valve replacement due to traumatic severe tricuspid regurgitation developed cavotricuspid isthmus-dependent counterclockwise atrial flutter. During a linear ablation using a contact force-sensing irrigated ablation catheter, the flutter could be terminated by a radiofrequency application within a deep pouch just below the bioprosthetic tricuspid valve.     

阿奇霉素连续与间歇注射给药治疗支原体肺炎的疗效与耐药性比较

为了比较阿奇霉素连续与间歇注射两种给药方式治疗支原体肺炎的临床疗效及耐药性,选取120例支原体肺炎患者,随机分为连续给药组(A组)与间歇给药组(B组),两组患者均连续治疗1个疗程(14d),比较临床疗效及耐药性情况。结果显示,两组患者在临床疗效、症状及体征消失时间方面均无明显差异(p>0.05),但治疗7d、14d后A组的最小抑菌浓度(MIC)值均明显低于B组(p<0.05)。结果表明,阿奇霉素的两种不同给药方式治疗支原体肺炎效果类似,但间歇给药法可减轻因连续给药带来的耐药性,对提高抗生素用药安全有一定价值。     

涉及桡骨远端骨巨细胞瘤的外科手术疗效比较

目的：探讨和比较不同手术术式治疗涉及桡骨远端的骨肉瘤的手术适应症选择,临床疗效和安全性。方法：将2005 年-2014 年我院收治的涉及到桡骨远端并进行外科手术治疗的骨巨细胞瘤患者共88 例进行回顾性分析。根据影像学Campanacci分级,主 要手术方法分为以下三种,分别为：A组：微波天线高温原位灭活,自体髂骨,异体骨粒符合骨水泥重建修复术;B：瘤骨切除并腓 骨移植术;C：瘤骨刮除灭活并原位植骨术。结合详实的随访资料对两组患者在术后的复发率,腕关节功能（Enneking）等情况给予 分析和评价。结果：A 组复发率为10.87 %,腕关节功能MSTS93 功能评分为26.32± 2.92分。B 组复发率为0,腕关节术后的 MSTS93 功能评分为22.85± 4.16 分。C 组复发率为30.24 %。腕关节术后的MSTS93 功能评分为26.97± 2.84 分。三组相比,A、 B 与C 组在复发率中有明显统计学差异（P<0.05）,A 组、C组的术后功能评分明显优于B 组（P<0.05）,但两组之间无统计学差异 （P>0.05）。A 组中有1 例切口表层感染,B 组中有2 例皮肤感染,均经加强换药后治愈。结论：瘤段切除手术能够有效的降低复发 率,但局部功能恢复较差,容易出现切口感染等并发症。微波灭活手术可以有效的杀灭肿瘤组织并保证良好的功能性,但复发率 相对较高。在临床工作中应根据患者具体病情和需要给予针对性的手术方案。     

Comparison of artificial insemination versus embryo transfer in lactating dairy cows

Conception rates (CR) are low in dairy cows and previous research suggests that this could be due to impaired early embryonic development. Therefore, we hypothesized that CR could be improved by embryo transfer (ET) compared with AI. During 365 days, 550 potential breedings were used from 243 lactating Holstein cows (average milk production, 35 kg/day). Cows had their ovulation synchronized (GnRH-7d-PGF(2alpha)-3d-GnRH) and they were randomly assigned for AI immediately after the second GnRH injection (Day 0) or for transfer of one embryo 7 days later. Circulating progesterone concentrations and follicular and luteal size were determined on Days 0 and 7. Pregnancy diagnosis was performed on Days 25 or 32 and pregnant cows were reevaluated on Days 60-66. Single-ovulating cows with synchronized ovarian status had similar CR on Days 25-32 with ET (n = 176; 40.3%) and AI (n = 160; 35.6%). Pregnancy loss between Days 25-32 and 60-66 also did not differ (P = 0.38) between ET (26.2%) and AI (18.6%). When single (n = 334) and multiple (n = 57) ovulators were compared, independent of treatment, multiple ovulators had greater (P < 0.001) circulating progesterone concentrations on Day 7 (2.7 ng/ml versus 1.9 ng/ml) and there was a tendency (P = 0.10) for a greater CR in multiple ovulators (50.9% versus 38.1%). However, there was no difference in CR between AI and ET cows with multiple ovulations (50.0% versus 51.7%). In single-ovulating cows, CR tended to be lower for AI than ET in cows ovulating smaller follicles (diameter < or = 15 mm; 23.7% versus 42.3%; P = 0.06) but not average-diameter follicles (16-19 mm; 41.2% versus 37.3%; P = 0.81) or larger (> or =20 mm; 34.3 versus 51.0%; P = 0.36) follicles. Thus, although ET did not improve overall CR in lactating cows, follicle diameter and number of ovulating follicles may determine success with these procedures.     

Comparison of global DNA methylation profiles in replicative versus premature senescence

DNA methylation is considered to play an essential role in cellular senescence. To uncover the mechanism underlying cellular senescence, we established the model of premature senescence induced by hydrogen peroxide (H(2)O(2)) in human embryonic lung fibroblasts and investigated the changes of genome methylation, DNA methyltransferases (DNMTs) and DNA-binding domain proteins (MBDs) in comparison with those observed during normal replicative senescence. We found that premature senescence triggered by H(2)O(2) exhibited distinct morphological characteristics and proliferative capacity which were similar to those of replicative senescence. The genome methylation level decreased gradually during the premature as well as replicative senescence, which was associated with the reduction in the expression of DNMT1, reflecting global hypomethylation as a distinct feature of senescent cells. The levels of DNMT3b and methyl-CpG binding protein 2 (MeCP2) increased in both mid-aged and replicative senescent cells, while DNMT3a and MBD2 were upregulated in the mid-aged cells. Only DNMT3b was elevated in the cells in the premature senescence persistence status. Additionally, the expression for DNMTs, MBD2 and MeCP2 was increased rapidly upon H(2)O(2) treatment. These results indicate that H(2)O(2)-induced premature senescence share some features of replicative senescence, such as basic biological characteristics and global hypomethylation while there are slight differences in the profile of methylation-associated enzyme expression. Oxidative damage may hence be a causative factor in epigenetic alteration partly responsible for cellular senescence.     

Comparison of Hi-C results using in-solution versus in-nucleus ligation

BackgroundChromosome conformation capture and various derivative methods such as 4C, 5C and Hi-C have emerged as standard tools to analyze the three-dimensional organization of the genome in the nucleus. These methods employ ligation of diluted cross-linked chromatin complexes, intended to favor proximity-dependent, intra-complex ligation. During development of single-cell Hi-C, we devised an alternative Hi-C protocol with ligation in preserved nuclei rather than in solution. Here we directly compare Hi-C methods employing in-nucleus ligation with the standard in-solution ligation.ResultsWe show in-nucleus ligation results in consistently lower levels of inter-chromosomal contacts. Through chromatin mixing experiments we show that a significantly large fraction of inter-chromosomal contacts are the result of spurious ligation events formed during in-solution ligation. In-nucleus ligation significantly reduces this source of experimental noise, and results in improved reproducibility between replicates. We also find that in-nucleus ligation eliminates restriction fragment length bias found with in-solution ligation. These improvements result in greater reproducibility of long-range intra-chromosomal and inter-chromosomal contacts, as well as enhanced detection of structural features such as topologically associated domain boundaries.ConclusionsWe conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0753-7) contains supplementary material, which is available to authorized users.     

Robustness of Multiple Comparison Procedures: Treatment versus Control

Computer simulation techniques were used to investigate the Type I and Type II error rates of one parametric (Dunnett) and two nonparametric multiple comparison procedures for comparing treatments with a control under nonnormality and variance homogeneity. It was found that Dunnett's procedure is quite robust with respect to violations of the normality assumption. Power comparisons show that for small sample sizes Dunnett's procedure is superior to the nonparametric procedures also in non-normal cases, but for larger sample sizes the multiple analogue to Wilcoxon and Kruskal-Wallis rank statistics are superior to Dunnett's procedure in all considered nonnormal cases. Further investigations under nonnormality and variance heterogeneity show robustness properties with respect to the risks of first kind and power comparisons yield similar results as in the equal variance case.     

Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

Background

Although pregabalin therapy is beneficial for neuropathic pain (NeP) by targeting the CaV??₂??-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects.

Results

We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaV??₂??-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaV??₂??-1 protein within peripheral nerve, dorsal root ganglia (DRG), and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaV??₂??-1 protein (but not CACNA2D1 mRNA) expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaV??₂??-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation.

Conclusions

Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaV??₂??-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.