Acute and Chronic Response to CRT in Narrow QRS Patients

Previous studies suggest that CRT may benefit narrow QRS patients with mechanical dyssynchrony (MD). We conducted an acute and chronic study, evaluating the response of heart failure patients with a narrow QRS to cardiac resynchronization therapy (CRT). ESTEEM-CRT was a multi-center, single-arm, feasibility study that evaluated ICD-indicated, medically-optimized patients with EF ≤ 35%, NYHA class III heart failure, QRS duration <120 ms, and MD as defined by the standard deviation of time to peak systolic velocity of 12 segments (Ts-SD). Sixty-eight patients received a CRT defibrillator, exercise testing, and echo exams, and 47 of these patients underwent invasive hemodynamic testing at implant. Follow-up was at 6 and 12 months. The average maximal improvement in LV dP/dt_max was minor (2 ± 2%). NYHA and quality of life scores were substantially improved at 6 and 12 months (P < 0.001), while exercise capacity and LV volumes were unchanged. The echo indices of MD were difficult to collect, discordant, and failed to predict clinical outcomes. ESTEEM-CRT patients with a narrow QRS and MD as defined in this study did not improve as measured by acute hemodynamics, chronic exercise performance, or reverse remodeling. These multi-center results support the notion that dyssynchrony indices are ineffective or at least require greater refinement for the selection of narrow QRS patients for CRT.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

The effect of fibrin polymers on thrombin-catalyzed plasma factor XIIIa formation

The effect of fibrin polymers on thrombin-catalyzed factor XIIIa formation was studied in afibrinogenemic plasma. Fibrin polymers derived from des A fibrinogen and des A,B fibrinogen increased sixfold the rate of thrombin-catalyzed factor XIIIa formation in the presence of EDTA. Calcium chloride accelerated factor XIIIa formation 14-fold in the presence of des A,B fibrinogen without increasing the rate of thrombin formation. Fibrinopeptides A and B had no effect on factor XIIIa formation in afibrinogenemic plasma. Des A,B fibrinogen reduced by 20- to 40-fold the thrombin concentration required to activate factor XIII. Glycyl-L-prolyl-L-arginyl-L-proline (gly-pro-arg-pro), a fibrin polymerization inhibitor, inhibited des A and des A,B fibrinogen from enhancing thrombin-catalyzed factor XIIIa formation. Gly-pro-arg- pro did not modify factor XIIIa formation in afibrinogenemic plasma and did not inhibit thrombin cleavage of the chromogenic substrate S-2238. These results demonstrate that fibrin polymers accelerate thrombin- catalyzed plasma factor XIIIa formation.     

AP-1和肿瘤的关系研究进展

转录因子AP-1(activatorprotein1),主要由Jun、Fos、ATF及JDP亚家族组成,亚家族单体以同源或异源二聚体的形式结合DNA靶序列,参与靶基因调节.对基因修饰小鼠和细胞的研究表明,AP-1参与细胞的正常生长和癌性转化过程,其在细胞中的作用取决于细胞类型、AP-1的组成和各组分的相对比例,也与刺激的种类密切相关.AP-1的活性受多种核因子调节,同时单体间也存在相互促进或拮抗作用.AP-1对各种刺激如应激、辐射或生长信号等作出生理或病理应答,参与细胞的增殖、分化和转化等过程,在肿瘤的形成、转移和侵袭中发挥重要作用,已经有学者研究通过抑制AP-1活性来发展抗肿瘤药物.     

Comparison of clinical and self-reported diagnoses for participants on a community-based arthritis self-management programme

OBJECTIVE: With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self- reported diagnoses of participants attending an Arthritis Self- Management Programme (ASMP). METHODS: Participants enrolling on the ASMP were asked to (a) identify their type of arthritis via a self- administered postal questionnaire and (b) obtain a written confirmation of their diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D. 12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in 534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and 96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The concordance rate for all other types of arthritis combined was lower at 60.5% (95% CI: 49.5-71.5%). There were no significant differences with respect to age, gender, education, physical functioning, duration of disease and number of GP visits between those who correctly identified their type of arthritis and those who did not. CONCLUSIONS: This study suggests that the majority of RA and OA participants attending an arthritis education programme can correctly identify their specific type of arthritis.      

A gain-of-function voltage-gated sodium channel 1.8 mutation drives intense hyperexcitability of A- and C-fiber neurons

Therapeutic use of general sodium channel blockers, such as lidocaine, can substantially reduce the enhanced activity in sensory neurons that accompanies chronic pain after nerve or tissue injury. However, because these general blockers have significant side effects, there is great interest in developing inhibitors that specifically target subtypes of sodium channels. Moreover, some idiopathic small-fiber neuropathies are driven by gain-of-function mutations in specific sodium channel subtypes. In the current study, we focus on one subtype, the voltage-gated sodium channel 1.8 (Na_v1.8). Na_v1.8 is preferentially expressed in nociceptors, and gain-of-function mutations in Na_v1.8 result in painful mechanical hypersensitivity in humans. Here, we used the recently developed gain-of-function Na_v1.8 transgenic mouse strain, Possum, to investigate Na_v1.8-mediated peripheral afferent hyperexcitability. This gain-of-function mutation resulted in markedly increased mechanically evoked action potential firing in subclasses of Aβ, Aδ, and C fibers. Moreover, mechanical stimuli initiated bursts of action potential firing in specific subpopulations that continued for minutes after removal of the force and were not susceptible to conduction failure. Surprisingly, despite the intense afferent firing, the behavioral effects of the Na_v1.8 mutation were quite modest, as only frankly noxious stimuli elicited enhanced pain behavior. These data demonstrate that a Na_v1.8 gain-of-function point mutation contributes to intense hyperexcitability along the afferent axon within distinct sensory neuron subtypes.