扩张型心肌病抗心肌β1与M2受体自身抗体的初步研究

目的研究抗β１与抗Ｍ２受体的自身抗体是否与扩张型心肌病（ＤＣＭ）有关。方法以心脏β１与Ｍ２受体细胞外第二环表位肽段的合成肽作为抗原，应用酶联免疫吸附测定（ＥＬＩＳＡ）技术检测５２例ＤＣＭ患者和４１例正常人血清中抗β１与Ｍ２受体的自身抗体。结果ＤＣＭ患者血清中有２２例（４２．３％）与２９例（５５．８％）的抗β１与抗Ｍ２受体的自身抗体，均显著高于正常人血清中仅５例（１２．２％）与４例（９．８％）相应抗体的检出（Ｐ＜０．０１）；ＤＣＭ患者血清中抗β１与Ｍ２受体的自身抗体滴度分别为１１０３与１１２８，远高于正常人１４０与１２４的相应抗体滴度（Ｐ＜０．０１）；心功能Ⅱ～Ⅲ级的阳性率是心功能Ⅳ级的２倍以上且抗体滴度大多在１１６０～１２５６０，而心功能Ⅳ级的抗体滴度全部在１２０～１８０。患者血清中抗β１与抗Ｍ２受体自身抗体的出现呈显著正相关（ｒ＝０．９６）。结论ＤＣＭ患者不仅存在抗心肌β１和Ｍ２的自身抗体而且他们的抗体滴度也明显高于正常对照组。     

Predictors and implications of residual plaque burden after coronary stenting: an intravascular ultrasound study

Background Residual plaque burden after coronary stenting may be visualized by use of intravascular ultrasound. Determinants and implications of residual atherosclerotic plaque burden after coronary stenting are not well established. In particular, the implications of residual plaque burden, after adjusting for confounding factors, are still unknown. Methods Sixty-two consecutive patients (age 56 ± 9 years) undergoing coronary stenting under intravascular ultrasound imaging guidance were prospectively studied. A total of 616 slices were analyzed (every 2 mm of stent length) from motorized pull-back recordings. Residual plaque burden was calculated as residual plaque/vessel area × 100. Results In 565 slices (89%), both residual plaque area and stent area could be measured. Mean residual plaque burden was 46.5% ± 6%. By use of multiple regression analysis, lesion plaque area and reference segment plaque burden were identified as independent predictors of residual plaque burden after stenting. In addition, a significant correlation was found between residual plaque burden and most relevant angiographic parameters at follow-up (including minimal lumen diameter, percent diameter stenosis, and loss index), which persisted after adjustment. Furthermore, stents with a residual plaque burden ≥46% had higher a restenosis rate (relative risk [RR] 4.4, 95% CI 1.09-18.2, P = .03). On logistic regression analysis, residual plaque burden (RR 4.8, 95% CI 4.1-5.6, P = .01) and diabetes (RR 4.3, 95% CI 3.6-5.1, P = .03) emerged as the only independent predictors of restenosis. Conclusions The amount of residual plaque burden after coronary stenting plays an independent role on the late angiographic outcome of these patients. (Am Heart J 2003;145:254-61.)     

Intravascular ultrasound assessment of the effect of laser energy on the arterial wall during the treatment of femoro-popliteal lesions: a CliRpath excimer laser system to enlarge lumen openings (CELLO) registry study

The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) registry included patients treated with modified excimer laser catheters for the endovascular treatment of peripheral artery disease affecting the superficial femoral artery (SFA) and proximal popliteal artery. The aim of this study was to assess, via intravascular ultrasound (IVUS) the dissections in the vessel wall following treatment with the laser catheters. IVUS grayscale images from the CELLO registry were systematically reviewed for dissections in the treated vessel segments by two investigators. Images from 33 patients; 66 pullbacks (1867 IVUS frames in 2 phases), were successfully matched frame-to-frame to evaluate identical segments of the treated vessels in the two phases; post-2 mm Turbo-Elite laser pilot channel creation and post Turbo-Booster laser atherectomy. Dissections were categorized as; (1) intimal, (2) medial, (3) intramural hematoma, and (4) adventitial according to the ACC Clinical Expert Consensus Document classification of dissections. An average of 57 frames was evaluated per pullback, giving a total of 3734 frames (1867 matched for pre-ablation (post channel creation) and post-ablation phases). Treatments with the modified Excimer laser catheters resulted in a significant increase in lumen area of 5.5?±?3.2-mm² (95% CI 4.3–6.8, p?<?0.0001) and reduction in plaque plus media volume of ?10.6?±?36.0 mm³ (95% CI ?25.8 to 4.6, p?=?0.1619) whilst giving rise to mainly intramural hematoma formations post Turbo-Booster laser treatment in 55% of frames assessed and 24% medial dissections with less than 1% adventitial disruption. The Excimer laser based Turbo-Booster treatment of peripheral artery lesions resulted in significant plaque debulking and increased lumen diameter with negligible degree of adventitial layer injury.     

Safety and tolerability of a single administration of AR-301, a human monoclonal antibody,in ICU patients with severe pneumonia caused by <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>: first-in-human trial

Purpose

Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.

Methods

Eligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤?30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start <?36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement.

Results

Thirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days.

Conclusions

Adjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.

     

Prevalence and severity of paravalvular regurgitation in the Artificial Valve Endocarditis Reduction Trial (AVERT) echocardiography study

OBJECTIVES: The purpose of this study was to determine the prevalence and severity of paravalvular regurgitation (PVR) in the Artificial Valve Endocarditis Reduction Trial (AVERT) cohort. BACKGROUND: The initial AVERT cohort consisted of 807 patients randomized to receive either a Silzone-coated prosthetic valve or a conventional prosthetic valve; early clinical reports showed higher rates of valve explant caused by PVR for Silzone-coated prosthetic valve. METHODS: Of the 678 eligible patients, 575 (85%) underwent postoperative transthoracic echocardiograms. The presence and severity of PVR were identified by color flow Doppler. Reviewers were blinded to the type of prosthetic valve and the demographic and clinical variables. RESULTS: Among those who underwent echocardiography (Silzone-coated prosthetic valve, n = 285 and conventional prosthetic valve, n = 290), 59% had prosthetic aortic valves, 32% prosthetic mitral valves, and 9% had both; demographic and clinical findings (i.e., prosthetic valve endocarditis, thromboembolism, bleeding, and all-cause death) were similar for the two groups. Echocardiographically determined PVR was present in 50 valves: Silzone-coated prosthetic valve, 29 of 285 (10%) and conventional prosthetic valve, 21 of 290 (7%, p = NS); the severity of PVR was similar in both groups. Kaplan-Meier analysis showed no significant differences in PVR at 24 months from valve implantation between the two groups (24-month event-free rate: 93% Silzone-coated prosthetic valve vs. 94% conventional prosthetic valve, p = NS). CONCLUSIONS: Excluding those patients who had initial prosthetic valve explant, the two-year echocardiographic follow-up of the AVERT cohort shows no statistically significant differences in the prevalence or severity of PVR in the Silzone-coated prosthetic valve compared with the conventional prosthetic valve. Further monitoring is warranted to determine whether these clinical outcomes remain similar on long-term follow-up.     

Rationale and design of diabetics exposed to telmisartan and enalapril (DETAIL) study

The DETAIL (diabetics exposed to telmisartan and enalapril) study will compare the long-term renal outcome of treatment with the angiotensin II receptor antagonist (ARA) telmisartan versus the angiotensin-converting enzyme (ACE) inhibitor enalapril in patients with mild-to-moderate hypertension and diabetic nephropathy. In short-term clinical studies, ACE inhibitors reduce microalbuminuria and, in the longer term, they are superior to conventional therapies in maintaining normal renal function. ARAs also appear to be renoprotective in diabetic animals. In this double-blind, parallel-group study, 252 patients with Type 2 diabetes and concurrent hypertension (mean seated systolic blood pressure < or = 180 mm Hg, on treatment seated diastolic blood pressure < or = 95 mm Hg) have been randomised to once-daily telmisartan 40 mg or enalapril 10 mg; doses are mandatorily titrated to 80 and 20 mg once daily, respectively, after 4 weeks. The primary endpoint will be the change from baseline in glomerular filtration rate (GFR) after 5 years of therapy, using the iohexol method and central laboratory analysis. The secondary endpoints to be evaluated will be: changes in GFR in relation to baseline after 1-4 years of therapy; percentage changes in albumin excretion rate after 1-5 years; and incidences of end-stage renal disease, cardiovascular events, all-cause mortality, and adverse events. The planned date for the completion of the study is 2005.     

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study

OBJECTIVES: The causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths. METHODS: Analyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients. Incidence rates of pre-AIDS deaths were compared to overall rates. Factors relating to pre-AIDS deaths were identified using Cox regression. RESULTS: Death rates declined from 15.6 to 2.7 per 100 person-years of follow-up (PYFU) between 1994 and 2001. Pre-AIDS incidence declined from 2.4 to 1.1 per 100 PYFU. The ratio of overall to pre-AIDS deaths peaked in 1996 at 8.4 and dropped to < 3 after 1998. The adjusted odds of dying following one AIDS defining event (ADE) increased yearly (odds ratio, 1.53; P < 0.001), conversely the odds of dying following three or more ADE decreased yearly (odds ratio, 0.79; P < 0.001). The proportion of deaths that followed an HIV-related disease decreased by 23% annually; in contrast there was a 32% yearly increase in the proportion of deaths due to known causes other than HIV-related or suicides. Injecting drug users (IDU) were significantly more likely to die before an ADE than homosexuals (relative hazard, 2.97; P < 0.0001) and patients from northern/eastern Europe (relative hazard, 2.01; P < 0.0001) were more likely to die pre-AIDS than southern patients. CONCLUSIONS: The proportion of pre-AIDS deaths increased from 1994 to 2001; however, the incidence of pre-AIDS deaths and deaths overall declined. IDU and subjects from northern/eastern Europe had an increased risk of pre-AIDS death. HIV-positive patients live longer therefore it is essential to continue to monitor all causes of mortality to identify changes.     

Prognostic value of erythrocyte sedimentation rate in ST segment elevation myocardial infarction: interaction with hyperglycaemia

OBJECTIVES: Many inflammatory markers are associated with an adverse prognosis after ST segment elevation myocardial infarction (STEMI). Hyperglycaemia may exacerbate this inflammatory response. We investigated whether the erythrocyte sedimentation rate (ESR) was associated with an adverse prognosis and whether this was mediated by glucose levels. RESEARCH DESIGN AND METHODS: It concerns a post hoc analysis of a prospective randomised trial. In 346 patients with STEMI treated with reperfusion therapy, we investigated long-term outcome. Patients with ESR in the upper quartile (>14 mm h(-1)) were compared to patients with a normal ESR. Hyperglycaemia was defined as admission glucose >or=7.8 mmol L(-1). Median follow up was 7.4 years (range: 5.7-8.3). MAIN OUTCOME MEASURES: All cause mortality, cardiovascular mortality, sudden death, death as a result of heart failure. RESULTS: Both elevated ESR and hyperglycaemia were associated with a worse prognosis and increased mortality. Elevated ESR was particularly associated with an increased risk of sudden death (OR: 3.3, 17% vs. 6%, P < 0.01) whereas hyperglycaemia was especially associated with an increased risk of death because of heart failure (OR: 6.5, 8% vs. 1%, P < 0.01). There was no association between increased ESR and elevated glucose levels. Multivariate analysis did reveal that both elevated ESR and admission glucose were independent predictors of long-term mortality. CONCLUSIONS: Elevated ESR and admission glucose are independent predictors of mortality in STEMI patients treated with reperfusion therapy. There is no association or interaction between glucose levels and the inflammatory response as reflected by ESR.