Optimizing implantable cardioverter-defibrillator treatment of rapid ventricular tachycardia: Antitachycardia pacing therapy during charging

BACKGROUND: Previous studies in implantable cardioverter-defibrillator (ICD) patients demonstrated the efficacy and safety of antitachycardia pacing (ATP) for rapid ventricular tachycardias (VT). To prevent shock delay in case of ATP failure, a new feature (ATP during charging) was developed to deliver ATP for rapid VT while charging for shock. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of this new feature. METHODS: In a prospective, nonrandomized trial, patients with standard ICD indication received an EnTrust ICD. VT and ventricular fibrillation (VF) episodes were reviewed for appropriate detection, ATP success, rhythm acceleration, and related symptoms. RESULTS: In 421 implanted patients, 116 VF episodes occurred in 37 patients. Eighty-four (72%) episodes received ATP during or before charging. ATP prevented a shock in 58 (69%) of 84 episodes in 15 patients. ATP stopped significantly more monomorphic (77%) than polymorphic VTs (44%, P = .05). Five (6%) episodes accelerated after ATP but were terminated by the backup shock(s). No symptoms were related to ATP during charging. In four patients, 38 charges were saved by delivering ATP before charging. Of 98 induced VF episodes, 28% were successfully terminated by ATP versus 69% for spontaneous episodes (P <.01). CONCLUSION: Most VTs detected in the VF zone can be painlessly terminated by ATP delivered during charging, with a low risk of acceleration or symptoms. ATP before charging allows delivery of two ATP attempts before shock in the same time that would otherwise be required to deliver only one ATP plus a shock. It also offers potential battery energy savings.     

Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells

Autoimmune disease results from the dysregulation of basic tolerogenic processes designed to control self/non-self-discrimination. Approaches to treat autoimmunity have focused historically on potent immunosuppressives that block the activation and expansion of antigen-specific T cells before they differentiate into pathogenic T cell responses. These therapies are very efficient in reducing clonal expansion and altering early signaling pathways. However, once the pathogenic responses are established (i.e., autoimmunity), the interventions are less effective on activated and differentiated T cell subsets (including memory T cells) or acting in the presence of an inflammatory milieu to abort immune responses at the target tissue and systemically. Moreover, the current immunotherapies require continuous use because they do not redirect the immune system to a state of tolerance. The continuous treatment leads to long-term toxicities and can profoundly suppress protective immune responses targeted at viruses, bacteria, and other pathogens. Over the past decade, there have been tremendous advances in our understanding of the basic processes that control immune tolerance. Among the most exciting has been the identification of a professional regulatory T cell subset that has shown enormous potential in suppressing pathologic immune responses in autoimmune diseases, transplantation, and graft vs. host disease. In this review, we summarize current efforts to induce and maintain tolerance in the autoimmune diabetes setting by using therapeutic vaccination with CD4(+)CD25(+) regulatory T cells. Emphasis will be placed on approaches to exploit regulatory T cells either directly or through the use of anti-CD3 immunotherapy.     

湖南省基本消灭丝虫病后的监测

目的：探讨自1986年湖南省达到基本消灭丝虫病后该病残存传染源消长规律及传播作用。方法：应用常规方法进行病原学、蚊媒和血清学纵向、横向监测以及流动人口监测，对薄弱环节采取适当的巩固措施。结果：在55个县（市）的横向监测中，末次检出微丝蚴阳性者系于1993年，蚊媒监测已有12年未查见人体幼丝虫感染蚊。血清学（IFAT）监测，平均人群抗体阳性率从1987年的13．15％至1996年降为1．06％，与非流行区人群水平相似。5个县（市）6个纵向监测点连续10－17年的观察结果，检获的11例残存微丝蚴血症者，有10例均在1－10年内阴转，另1例至14年未阴转。蚊媒监测，2个马来丝虫病监测点均未查见幼丝虫，4个班氏丝虫病监测点于第1－3年查见幼丝虫，其自然感染率为0．38％－1．98％，第4年以后均为阴性。结论：湖南省基本消灭丝虫病后残存传染源逐年减少，丝虫病传播已被阻断。     

置起搏器的老年人心律失常分析及随访观察

分析２５例置永久心脏起搏器的老年人缓慢性心律失常，其中以病态窦房结综合征（ＳＳＳ）多见（２２例）。原发病以冠心病为主（２１例）。随访２～６９个月，全部患者原有症状消失，生活自理。置心室按需型起搏器已能达到治疗目的，尤以双腔起搏器（ＤＤＤ）之类的生理性起搏器者生活质量明显提高。置起搏器后单纯型ＳＳＳ者心律失常有所改善，但仍有１６％发生房颤，置ＤＤＤ者尚可发生起搏介入性心动过速，随访及时发现和处理新的心律失常不可忽视。     

The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the disease were investigated in this study. Either the expression level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relationship between mdm2 and p53 revealed that mdm2 gene expression in HCC without p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indicated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasiveness of HCC through inactivating the tumor-suppressor function of the p53 gene. Received: 8 September 1997 / Accepted: 17 December 1997     

Stem water cryogenic extraction biases estimation in deuterium isotope composition of plant source water

The hydrogen isotope ratio of water cryogenically extracted from plant stem samples (δ²H_{stem_CVD}) is routinely used to aid isotope applications that span hydrological, ecological, and paleoclimatological research. However, an increasing number of studies have shown that a key assumption of these applications—that δ²H_{stem_CVD} is equal to the δ²H of plant source water (δ²H_source)—is not necessarily met in plants from various habitats. To examine this assumption, we purposedly designed an experimental system to allow independent measurements of δ²H_{stem_CVD}, δ²H_source, and δ²H of water transported in xylem conduits (δ²H_xylem) under controlled conditions. Our measurements performed on nine woody plant species from diverse habitats revealed a consistent and significant depletion in δ²H_{stem_CVD} compared with both δ²H_source and δ²H_xylem. Meanwhile, no significant discrepancy was observed between δ²H_source and δ²H_xylem in any of the plants investigated. These results cast significant doubt on the long-standing view that deuterium fractionation occurs during root water uptake and, alternatively, suggest that measurement bias inherent in the cryogenic extraction method is the root cause of δ²H_{stem_CVD} depletion. We used a rehydration experiment to show that the stem water cryogenic extraction error could originate from a dynamic exchange between organically bound deuterium and liquid water during water extraction. In light of our finding, we suggest caution when partitioning plant water sources and reconstructing past climates using hydrogen isotopes, and carefully propose that the paradigm-shifting phenomenon of ecohydrological separation (“two water worlds”) is underpinned by an extraction artifact.

The analysis of the stable isotope ratios of plant source water (δ_source) is a powerful tool enabling the elucidation of a range of plant physiological, ecological, and hydrological processes from scales ranging from individual plants to the planet. δ_source provides a foundation on which to form isotope signals of transpired water vapor and plant-derived biomarkers (i.e., cellulose and lipids) and thus is of high relevance to studies of terrestrial water fluxes (1, 2) and paleoclimate reconstructions (3, 4). δ_source also contains information on the spatial and temporal origins of water used by plants and so is commonly used for investigating plant water uptake patterns under natural conditions (5, 6). Moreover, dual-isotope (δ²H and δ¹⁸O) analysis of δ_source was critical in formulating the paradigm-shifting “two water worlds” (TWW) hypothesis, whereby ecohydrological separation exists between plant-accessible soil water pools and those recharging streams and groundwater (7, 8).Elucidation of the foregoing processes rest on the assumption that water extracted from plant stems is isotopically identical to water taken up by plant roots. Plant stem water is typically extracted with the cryogenic-vacuum distillation technique; δ generated with this method is hereinafter referred as δ_{stem_CVD} (9). For δ_{stem_CVD} to be an accurate indicator of δ_source (i.e., δ_{stem_CVD} = δ_source), two prerequisites must be met: 1) isotope change does not occur during root uptake and/or xylem transport of the source water (prerequisite I) and 2) stem water cryogenic extraction is a robust approach toward isotope recovery of xylem water (prerequisite II). The “δ_{stem_CVD} = δ_source” assumption is generally valid for oxygen isotopes of water, but numerous studies have used hydrogen isotopes to assess source water, and here this assumption has faced scrutiny, as multiple studies have reported significant depletion in δ²H_{stem_CVD} compared with δ²H_source in plants from various habitats (10–18).A frequently invoked explanation for the observed δ²H_{stem_CVD} depletion is a violation of prerequisite I, as it is believed that symplastic uptake of source water into the root xylem can give rise to hydrogen isotope fractionation (10, 11, 13, 19). The available evidence (10, 11) in support of such an explanation is largely peripheral, because direct, unambiguous confirmation of water uptake/transport-related fractionation would require a comparison of deuterium in source water and water transported within xylem conduits (δ²H_xylem). However, this type of comparison is difficult owing to the technical challenges in obtaining targeted measurements of δ²H_xylem in most plants. Intriguingly, in a field-grown riparian tree species (Populus euphratica) in which δ²H_xylem measurement was made possible with the aid of a syringe-aided xylem sap bleeding technique, no significant difference was observed between δ²H_xylem and δ²H_source (12). This led to the suggestion that, at least for the investigated species, δ²H_{stem_CVD} depletion arises not from a violation of prerequisite I, but rather from a violation of prerequisite II. The violation of prerequisite II has been deemed possible (12, 17) based on the argument that hydrogen isotope heterogeneity could be present within the bulk stem water (i.e., the outside xylem water may carry a metabolism-induced, more-depleted δ²H signature compared with the xylem water), potentially causing the stem water extraction technique to artifactually underestimate δ²H_xylem.Given the controvertible state of knowledge regarding the mechanism driving δ²H_{stem_CVD} depletion, it is imperative for us to build a better and more comprehensive understanding of the isotopic relationships among cryogenic extracted bulk stem water, source water, and xylem water in different plants, so as to put the application of the stem water cryogenic extraction technique in diverse fields on firmer ground. In this context, it should be pointed out that the xylem water direct sampling technique (12) is applicable only to a few riparian tree species. Recently, a new method relying on laser-enabled isotope measurement of water vapor in equilibrium with xylem water has demonstrated potential for in situ continuous monitoring of xylem isotope signatures in trees (20, 21); however, the method needs further development before it becomes broadly applicable to different plant types. Thus, a more generally applicable method is needed for determining xylem water signature across diverse plant types.Toward this goal, and capitalizing on the well-recognized mass balance-dictated principle that the isotopic composition of steady-state (SS) plant transpiration is identical to that of the xylem water supplying the plant canopy, we custom-designed a measurement system to enable independent quantification of xylem water isotope composition through isotope measurement of SS plant transpiration. This measurement system conferred the ability to compare values of δ_{stem_CVD}, δ_source, and δ_xylem across a number of plant species of varying native habitats. The data allowed us to confirm the common presence of δ²H_{stem_CVD} depletion across all plant types measured, and also to demonstrate that this phenomenon is caused by cryogenic extraction-associated artifact and not by water uptake/transport-related fractionation. We also performed a rehydration experiment to illustrate that the extraction artifact is unrelated to within-stem isotope heterogeneity as has been recently suggested, but rather is more likely linked to a deuterium-exchange process that occurs dynamically during cryogenic extraction. Using the TWW hypothesis as an example, we further discuss the ramifications for ecological/hydrological queries that rely on accurate isotopic information on plant source/xylem water.     

Correlates of carotid artery stiffness in young adults: The Bogalusa Heart Study

Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for prevention.