Pacemaker Mediated Tachycardias In Single Chamber Rate Responsive Pacing

LAU, C.-P., ET AL.: Pacemaker Mediated Tachycardias In Single Chamber Rate Responsive Pacing. Although pacemaker mediated tachycardias are classically associated with dual chamber pacemakers, single chamber rate responsive pacemakers are also susceptible to such tachycardias under special circumstances. A unipolar activity sensing rate responsive pacemaker (Activitrax 8403) was implanted in an 83-year-old man with complete atrioventricular block. The pacemaker was programmed at an output of 5 V, activity threshold medium, rate response 5, and lower and upper rates of 70 and 125 beats/min, respectively. He presented with palpitations at rest and muscle twitching of the pacemaker pocket 4 months after implantation. Examination confirmed that the pacemaker had flipped over, resulting in pocket pacing which in turn activated the activity sensor, resulting in a rate response. The increase in pacing rate lead to a higher frequency of pocket pacing, thus leading to positive feedback increase in rate. With the patient at rest, pacemaker mediated rates were 106, 91, and 74 beats/min at low, medium and high thresholds, respectively. Decreasing the output to 2.5 V eliminated pocket pacing and the tachycardia. As a result of the reversal of the pacemaker, a similar rate response during exercise could only be achieved at a more sensitive rate responsive setting. Thus, pacemaker mediated tachycardia can complicate pacemaker "flipping" in single chamber activity sensing rate responsive pacemakers. Methods for the avoidance and treatment of pacemaker flipping are discussed. A review of other sensor mediated tachycardias is also presented.     

α‐Actinin‐4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin‐induced podocyte injury

Aim: Glucocorticoid therapy has been used in childhood nephrotic syndrome since the 1950s, where the characteristic change is effacement of the actin‐rich foot process of glomerular podocytes. Recent studies have shown that glucocorticoids, in addition to their general immunosuppressive and anti‐inflammatory effects, have a direct effect on podocytes, regulate some apoptotic factors, and increase the stability of actin filaments. However, the precise mechanism(s) underlying the protective effects of glucocorticoids on podocytes remain unclear. It is known that adriamycin (ADR) can induce podocyte foot process effacement and trigger massive proteinuria in rodent models. However, few reports have examined the direct role of ADR in podocyte actin rearrangement in vitro. In this study, we investigated how ADR directly induced podocyte actin cytoskeleton rearrangement and further analyzed how dexamethasone prevented such injury. Methods: We used confocal microscopy to assess podocyte actin rearrangement. Western blot analysis and real‐time polymerase chain reaction were performed to measure the protein and mRNA levels of α‐actinin‐4. Results: We demonstrated that there was a time‐dependent ADR‐induced podocyte actin rearrangement with less than 12 h of ADR treatment in cultured podocytes. Dexamethasone could protect podocytes from ADR‐induced injury and also stabilize the expression of α‐actinin‐4. Conclusion: This study showed that dexamethasone had direct effects on podocytes: α‐actinin‐4 may be one of the potential target molecules.     

基于反转恢复实时快速小角度激发成像的心肌T1值量化方法

目的验证反转恢复实时快速小角度激发(IR-rttfl)成像的心肌T1量化方法。方法对仿体、健康志愿者和心肌坏死患者分别进行成像,在3.0T磁场中使用IR-rttfl的扫描方法量化心肌T1值,与MOLLI方法的结果进行对比,并将T1量化的结果用于分析心肌的异常区域。结果 IR-rttfl方法将扫描时间缩短到6s以内,T1量化结果比MOLLI方法更准确,并且能够有效区分患者心肌的异常区域。结论这种方法能够有效抑制心律不齐造成的影响,提高心肌T1量化结果的准确性,对心肌坏死的诊断具有重要意义。     

Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers

Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers. APMIS 2009; 117: 880–5. Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia‐inducible factor 1α (HIF1α) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1α is upregulated not only by hypoxia but also by genetic alterations in HIF1α‐related genes, including VHL. Cullin 2 (CUL2) interacts with the trimeric VHL‐elongin B‐elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1α. The aim of this study was to explore whether HIF1α and CUL2 genes are somatically mutated, and contribute to HIF1α activation in common human cancers. For this, we have analyzed the coding region of oxygen‐dependent degradation domain of HIF1α in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single‐strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in CUL2 in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one HIF1α mutation (p.Ala593Pro) in the hepatocellular carcinomas (1/47; 2.1%), but none in other cancers. We found two CUL2 frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2/41). Our data indicate that somatic mutation of HIF1α is rare in common cancers, and somatic mutation of CUL2 occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither HIF1α nor CUL2 mutation may play a central role in HIF1α activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.     

A challenge to chronic kidney disease in Asia: The report of the second Asian Forum of Chronic Kidney Disease Initiative

Background: The Asian Forum of Chronic Kidney Disease Initiative started in 2007 in Hamamatsu, Japan when delegates from 16 countries joined together to facilitate collaboration in studying chronic kidney disease (CKD) in the Asia–Pacific region. Based on the outcome of the first meeting, the second meeting was organized as a consensus conference to frame the most relevant issues, and develop research recommendations and action plan. Proceedings: The meeting was held on 4 May 2008 as a pre‐conference meeting to the 11th Asian Pacific Congress of Nephrology in Kuala Lumpur. This meeting consisted of three sessions: Session I was dedicated to the estimation of glomerular filtration rate and the standardization of serum creatinine measurements. Session II discussed specific considerations in the aetiology of and risk factors for end‐stage renal disease in Asia. We concluded that there were regional specific problems that might lead to a very high prevalence of end‐stage renal disease. Session III discussed the issue of facilitation of coordination and integration of the CKD initiative between developed and developing countries in the Asia–Pacific region. Conclusion: The following action plans were formulated: (i) validating the existing global estimated glomerular filtration rate equation or creating a new one using serum creatinine standardized by a central laboratory; (ii) establishing a pan‐Asian CKD registry to facilitate risk analysis of CKD and its comorbidities; (iii) adapting existing clinical practice guidelines for CKD detection and management to address specific problems in this region; and (iv) working closely with other international professional organizations to promote manpower development and education in different aspects of CKD in developing countries.     

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation

Abstract In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS ( P < 0.05) or tubercle bacilli ( P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1β, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.