可溶性CD40配体与急性冠状动脉综合征的关系

目的探讨急性冠脉综合征(ACS)患者血清可溶性CD40L水平变化的临床意义。方法正常对照组22名,将患者分为稳定型心绞痛(SA)组20例、不稳定型心绞痛(UA)组22例和急性心肌梗死(AMI)组15例。其中20例(UA组15例、AMI组5例)行经皮冠状动脉介入术(PCI)。所有受试者均采用双抗夹心酶联免疫测定法(ELISA)对sCD40L水平进行检测,同时观察冠脉造影和PCI术前和术后30dsCD40L的水平变化。结果①UA组及AMI组血清sCD40L水平明显较对照组高(P<0.01)。②UA组与SA组相比差异有统计学意义(P<0.05),AMI组明显较SA组高(P<0.01)。③SA组与对照组相比差异有统计学意义(P<0.01)。④AMI组患者血清sCD40L水平与UA组差异有统计学意义(P<0.01)。⑤PCI后30d血清sCD40L明显低于PCI前(P<0.01)。结论血清可溶性sCD40L的升高在ACS发生和发展中起重要作用,是反应斑块不稳定性的指标之一。     

Soleus and lateral gastrocnemius H‐reflexes during standing with unstable footwear

Introduction: Unstable footwear has been shown to increase lower extremity muscle activity, but the reflex response to perturbations induced by this intervention is unknown. Methods: Twenty healthy subjects stood in stable and unstable footwear conditions (presented randomly) while H‐reflex amplitude and background muscle activity were measured in the soleus and lateral gastrocnemius (LG) muscles. Results: Wearing unstable footwear resulted in larger H‐reflexes (normalized to the maximal M‐wave) for the LG (+12%; P = 0.025), but not for the soleus (+4%; P > 0.05). Background activity of both muscles was significantly higher in the unstable condition. Conclusions: The H‐reflex facilitation observed with unstable footwear was unexpected, as challenging postural conditions usually result in reflex depression. Increased muscle activity, decreased presynaptic inhibition, and/or more forward postural position may have (over‐)compensated the expected reflex depression. Differences between LG and soleus H‐reflex modulation may be due to diverging motor unit recruitment thresholds. Muscle Nerve 51 :764–766, 2015     

Additional antianginal and anti-ischemic efficacy of mibefradil in patients concomitantly treated with long-acting nitrates for chronic stable angina pectoris

Background: Mibefradil, a newly approved antihypertensive and antianginal drug, is the first member of a new class of calcium antagonists (CAs), the tetralol derivatives, that selectively blocks T-type Ca²⁺ channels in contrast to classical CAs which, at therapeutic concentrations, block only L-type Ca²⁺ channels. Since patients with chronic stable angina pectoris typically may be treated with the combination of a long-acting nitrate and a CA, the additive efficacy and safety of mibefradil in combination with nitrate therapy needs to be determined. Hypothesis: This study was designed to assess the efficacy, tolerability, and safety of mibefradil when added to longacting nitrate therapy in patients with chronic stable angina pectoris. Methods: Following a 1 -week placebo run-in period, patients were randomized to receive either mibefradil 50 mg (n = 96) or placebo (n = 93) once daily in addition to their nitrate therapy. After 2 weeks of active treatment, patients receiving the mibefradil were force titrated to 150 mg once daily for an additional 2 weeks. Exercise tolerance tests (ETTs) were per formed at the end of Weeks 2 and 4; patients also maintained an anginal diary during the 4-week treatment period. Results: After 2 weeks of treatment with 50 mg mibefradil (within the current recommended dose range), a statistically significant but modest increase in total exercise duration was observed (treatment effect 16.4 s, p = 0.04). Similarly, there was a significant increase in time to onset of ischemia (treatment effect 26 s, p = 0.008). The adverse event profile of the 50 mg dose was indistinguishable from placebo, indicating that this dose was extremely well tolerated. At Week 4, the mibefradil-treated patients were taking 150 mg, which is above the current recommended dose range. The increase in total exercise duration was larger for the mibefradil 150 mg group than for the placebo group. For the intent-to-treat population, this difference did not reach statistical significance, whereas in the standard population it did (treatment effect 21 s, p = 0.05). The other two ETT variables, time to onset of angina and time to onset of 1 mm ST-segment depression, demonstrated significantly greater effect with mibefradil 150 mg (treatment effects 40 s, p = 0.002, and 55 s, p < 0.001, respectively, for the intent-to-treat population). Mibefradil 150 mg was associated with more adverse events than placebo, specifically, dizziness, leg edema, and postural hypotension. Conclusions: This study demonstrates that mibefradil 50 mg once daily in the setting of the background long-acting nitrate therapy produces additive antianginal and anti-ischemic effects and is extremely well tolerated.     

阿托伐他汀对不稳定型心绞痛患者C-反应蛋白的影响

目的探讨阿托伐他汀对不稳定型心绞痛(UA)患者C-反应蛋白(CRP)和血脂的影响。方法选择76例UA患者,随机分成两组,治疗组给予常规治疗加阿托伐他汀每晚10mg口服,对照组给予常规治疗,持续8周。然后比较两组患者治疗前、后CRP和血脂水平的变化。结果经用药后治疗组血清CRP水平及血脂水平较对照组降低明显,与对照组相比差异有统计学意义(P<0.05)。结论阿托伐他汀可降低UA患者血清CRP及血脂水平。     

Ludwig’s angina by Salmonella Typhi: A clinical dilemma

Salmonella Typhi has rarely been associated with focal abscesses; and in literature, there is no evidence of its association with abscesses in the neck spaces. Ability of Salmonella Typhi to invade and localise in the neck spaces not only poses a diagnostic challenge but also underscores the necessity to understand the mechanisms that facilitate Salmonella Typhi to establish infections at sites completely non-traditional to the organism.     

Optimal medical therapy is a proven option for chronic stable angina

The authors of the meta-analysis of a percutaneous coronary intervention (PCI)-based invasive strategy for improving prognosis for the treatment of angina conclude that a pooling of data from various studies can be sufficiently powered to evaluate the impact of PCI on long-term mortality. However, most randomized coronary artery patient trials have insufficient power to detect significant differences in hard end points. Randomized trials in patients with chronic stable angina enroll few patients who are over age 65 years, have depressed ventricular function, have clinical instability, or who have undergone previous coronary artery bypass grafting (CABG) or PCI. "Medical therapy" today no longer means the absence of PCI, but rather the presence of intensive, evidence-based pharmacologic intervention. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial randomized 2,287 patients to optimal medical therapy alone or optimal medical therapy plus PCI. Optimal medical therapy consisted of antiplatelet therapy, anti-ischemic therapy, and aggressive lipid and blood pressure control. Based on the strength of the evidence, the author of this commentary recommends more-aggressive medical therapy for patients with moderate-to-severe angina, and PCI or CABG for many patients in whom symptoms persist. Optimal medical therapy is a proven option for chronic stable angina.     

Variable response to atrial pacing after intravenous propranolol in patients with stable exertional angina

The effect of propranolol administration on regional coronary haemodynamics were investigated in 14 patients with stable exertional angina and isolated left anterior descending artery disease. Thermodilution was used to measure great cardiac vein flow (GCVF) and anterior regional coronary resistance (ARCR) under control conditions, at peak atrial pacing, after i.v. propranolol administration (0.1 mg kg-1) and at the peak of repeated atrial pacing. Propranolol did not change peak pacing heart rate, systolic blood pressure or double product. Peak pacing GCVF decreased slightly but non-significantly after drug administration from 84 +/- 20 to 79 +/- 24 ml min-1, while ARCR increased, but again non-significantly, from 1.36 +/- 0.44 to 1.45 +/- 0.45. Analysis of individual patient responses revealed that propranolol prolonged peak pacing time and hence peak pacing heart rate (from 126 +/- 24 to 140 +/- 23 beats min-1, P less than 0.05) in five patients. In such patients, peak pacing systolic blood pressure was lower than the pre-propranolol atrial pacing (145 +/- 35 vs 165 +/- 33, P less than 0.001) so that double product remained unchanged. Moreover, peak pacing ARCR did not change after propranolol (pre-propranolol 1.47 +/- 0.46, after propranolol 1.40 +/- 0.56 mmHg.ml-1.min, P = ns) while it increased significantly in the nine patients who did not improve after the drug (before propranolol 1.30 +/- 0.44, after propranolol 1.48 +/- 0.41 mmHg.ml-1.min, P less than 0.02). These data suggest that the response to atrial pacing after i.v. propranolol administration is variable as some patients tolerate higher heart rates while others do not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris

Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6− subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm–Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm–Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6− subjects (P = 0.017; 95% CI, 1.73–6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23–7.15). Analyses of telomere lengths between iciHHV-6− without angina, iciHHV-6− with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6− subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.Human herpesvirus (HHV)-6A (1) and HHV-6B (2) are worldwide ubiquitous human pathogens belonging to the β herpesvirus subfamily. Primary HHV-6B infection occurs early in life (6 mo to 3 y) and causes roseola or exanthem subitum (3). Fewer details exist on the epidemiology of HHV-6A, and at present, primary HHV-6A infections have not been linked to diseases. The fact that HHV-6B is more widely distributed, acquired earlier in life, and likely to provide cross-protective immunity (HHV-6A and HHV-6B proteins are 80% identical) could explain, at least in part, the apparent lack of disease association with primary HHV-6A infection.All herpesviruses possess a bimodal replicative cycle that allow them to replicate and generate new infectious viral particles or allow them to enter a state of latency where viral gene expression is minimal and no viruses are produced. Latency allows these viruses to escape immune surveillance enabling them to persist for life within their host. Reactivation from latency and viral replication can be triggered by several stimuli such as UV exposure or hormonal changes. Depending on the immunological competency of the host, such secondary infections can either be contained (asymptomatic) or disseminated, often resulting in pathogenic outcomes (4). HHV-6A and HHV-6B latency is unique among human herpesviruses in that these viruses have developed the ability to integrate their genomes into human chromosomes (5), much like Marek’s disease virus (MDV), whose genomic integration is tightly associated with lymphoma development (6). HHV-6 integration can occur in several distinct chromosomes but invariably takes place within the telomeric regions (7). When integration occurs in germinal cells, integrated HHV-6A and HHV-6B can be passed on to descendants according to Mendelian genetics (8). Consequently, individuals with such inherited chromosomally integrated HHV-6 (iciHHV-6) carry a copy of the viral genome in every cell of their body. Diagnosis of iciHHV-6 is easily made by measuring and comparing the relative number of HHV-6 DNA copy per cell either using quantitative PCR (qPCR) and/or digital droplet PCR (9, 10). iciHHV-6+ subjects have approximately one million copies per million cells, whereas those that have acquired HHV-6 naturally typically have between 60 and 80 viral DNA copies per million cells (11). In vitro and in vivo studies have indicated that, once integrated, HHV-6 can express genes and reactivate from latency with pathogenic outcomes (12–15). Based on several studies, including the present one, we estimate that between 40 and 70 million individuals worldwide carry iciHHV-6 (7).It is well established that the self-renewal potential of cells is directly proportional to telomere lengths and telomerase activity (16, 17). It is also known that the shortest telomere, not average telomere length, is critical for cell viability and chromosome stability (18). When the number of telomeric repeated sequences (TRSs) falls below 13, chromosomal instability is observed (19). Integration of HHV-6 within the telomeric region is unlikely to be without consequences (7). In fact, Huang et al. recently reported that the chromosome harboring integrated HHV-6 is often the shortest, suggesting that integration affects telomeric integrity (20). Several diseases are linked with telomere dysfunctions and/or telomerase mutations such as cardiovascular diseases, hematopoietic dysfunction, pulmonary fibrosis, liver disease, degenerative diseases, and cancer (21–31). Alterations within telomeric regions are therefore a likely cause for cellular dysfunctions linked to diseases, but many of the factors affecting telomere integrity remain to be identified. Interestingly, by compiling several small independent studies, it has been reported that iciHHV-6 is 2.3 times more frequent (P < 0.001) in diseased (various diseases) individuals relative to healthy ones, suggesting that iciHHV-6 represents a risk factor in disease development (32). Knowing this, we undertook a large-scale population study to assess the prevalence of iciHHV-6 in the CARTaGENE (CaG) cohort. The CaG biobank (www.cartagene.qc.ca), consists of both biological samples and complete medical records on the health and lifestyles of randomly selected Quebecers (Canada) between 40 and 69 y of age. The bank contains in-depth information on nearly 20,000 individuals (17% born outside Canada), including sociodemographic, lifestyle, health data, and familial history of disease, 190 physiological parameters, biochemical analyses, and hematological analyses (33). Genomic DNA extracted from blood-spotted filters was used for HHV-6 qPCR and droplet digital PCR (ddPCR) analyses. Because iciHHV-6 individuals carry one viral genome copy per cell, identification of subjects with iciHHV-6 is easily made (9, 34). The overall prevalence of iciHHV-6 in the CaG cohort was determined, and disease prevalence in subjects with iciHHV-6 was compared with that of subjects without iciHHV-6.     

麝香保心丸治疗不稳定性心绞痛的临床疗效观察

[目的]观察麝香保心丸治疗不稳定性心绞痛的临床疗效。[方法]将110例不稳定性心绞痛患者,随机分为观察组和对照组,观察组采用麝香保心丸治疗,对照组采用单硝酸异山梨醇酯片治疗,疗程30 d,观察心绞痛每周的平均发作次数及硝酸甘油的每周用量。[结果]观察组与对照组治疗后心绞痛发作次数、硝酸甘油用量方面优于治疗前,且观察组优于对照组,两组间差异有统计学意义(P0.05)。[结论]麝香保心丸治疗不稳定性心绞痛具有一定的临床疗效,可能优于单硝酸异山梨酯片。