Abciximab therapy improves 1-month survival rate in unselected patients with acute myocardial infarction undergoing routine infarct artery stent implantation

Background The impact of abciximab therapy on mortality in unselected patients with acute myocardial infarction (AMI) undergoing routine primary infarct-related artery (IRA) stent implantation is not yet defined, and previous randomized studies have produced conflicting results. Methods A strategy of IRA stenting alone as opposed to IRA stenting plus abciximab was compared in a series of 561 consecutive unselected patients with AMI. Abciximab tretament was strongly encouraged for all patients. The contraindication for abciximab therapy was a high risk of major bleeding as assessed by the operator before mechanical intervention. Results Of 561 patients, 348 patients underwent abciximab therapy and 213 underwent primary IRA stenting alone. The 1-month overall mortality rate was 2.9% in the abciximab group and 10.8% in the stent alone group (P < .001). The relative reduction in mortality rate was 73% for patients overall, 77% in the subset of patients aged ≤70 years (mortality rate, 1.2% vs 5.2%, P = .020), 57% in patients aged >70 years (7.7% vs 18%, P = .043), 63% in patients with cardiogenic shock (17% vs 46%, P = .022), and 77% in patients without cardiogenic shock (1.3% vs 5.6%, P = .002). Multivariate analyses on the basis of all patients, and on the subset of patients aged ≤70 years, showed that abciximab therapy was independently related to the risk of death at 1 month. No differences were seen between groups in the procedural success rate (99.1% vs 98.1%) or in the incidence rates of nonfatal reinfarction (0.3% vs 1.9%) or repeat target vessel revascularization (1.7% vs 1.9%). Conclusion The results of this study strongly support the use of abciximab therapy in nonselected patients with AMI undergoing routine IRA stent implantation. The mechanism of the clinical benefit of abciximab was not related to the patency of the IRA. (Am Heart J 2002;144:315-22.)     

A new type of congenital dysfibrinogenaemia with defective fibrin lysis—Dusard syndrome: possible relation to thrombosis

S ummary . Congenital dysfibrinogenaemia is described in three members of a family presenting with recurrent thrombosis and in two other young members not yet affected. An abnormality in the polymerization of fibrin monomers was noted. In addition, the pathological fibrin clots were found to be less sensitive to degradation by a post venous occlusion euglobulin solution than normal fibrin. After fibrin clot incubation with lys-plasminogen at different concentrations, the biological activity of plasminogen in patient fibrin clot on S 2251 after SK-addition, was less than that observed with normal fibrin. It is speculated that defective in vivo thrombolysis might explain the recurrent thrombosis observed in this family. This finding represents a new concept in understanding thromboembolic diseases.     

Acute myocardial infarction and underlying stenosis severity.

OBJECTIVES: The objective of this study was to investigate the underlying stenosis severity of the culprit lesion in acute myocardial infarction. BACKGROUND: It is widely believed that myocardial infarction often occurs in angiographically mild luminal stenosis. This, however, is in contradiction with experience from interventional practice in primary PCI. METHODS: We performed quantitative coronary angiography (QCA) in 250 consecutive patients referred for acute percutaneous coronary intervention (PCI) because of acute myocardial infarction (AMI). Fundamental for analysis was that a realistic estimate of underlying luminal narrowing before the infarction could be made angiographically that QCA could be performed and that one of two criteria was met: (1) spontaneous reflow allowing assessment of the lumen proximal and distal to the culprit lesion, or (2) coronary artery closed at arrival but reflow after uncomplicated wiring allowing assessment of the lumen proximal and distal to the culprit lesion. RESULTS: Of 250 consecutive patients (mean age 61.7 +/- 12.7 years, 48 women) referred for acute PCI, 156 patients (62%) fulfilled at least one of the above criteria for reliable QCA. In 151 of these patients (96%) the severity of the underlying stenosis was >50% and in 103 (66%) it was >70%. There were no differences in stenosis severity between the left anterior descending [LAD, (72 +/- 13)%, n = 57], left circumflex [Cx, (74 +/- 10)%, n = 20], and right coronary artery territory [RCA, (74 +/- 12)%, n = 76] (ANOVA, P = 0.76). There were no differences in stenosis severity between women [(73 +/- 13)%, n = 36] and men [(75 +/- 11)%, n = 120; P = 0.35]. CONCLUSION: In contrast to what is often believed, the majority of myocardial infarctions occurs in significant stenosis.     

A Critical Role for CD48 Antigen in Regulating Alloengraftment and Lymphohematopoietic Recovery After Bone Marrow Transplantation

The binding of CD2, present on T cells, to its counterreceptor CD48facilitates adhesion, signaling, alloantigen-induced cytokine production, and cytotoxic T-lymphocyte responses. Becausethese T-cell functions have been implicated in graft-versus-hostdisease (GVHD) pathogenesis, we have analyzed the effects of theCD2:CD48 pathway on GVHD mediated by CD4⁺ andCD8⁺ T cells infused into sublethally irradiatedrecipients. CD4⁺ T-cell-mediated, and to a lesserextent, CD8⁺ T-cell-mediated GVHD was inhibited byCD2 + 48 monoclonal antibody (MoAb) infusion. To assessthe effects of combined MoAb infusion on alloengraftment, two differentalloengraftment bone marrow transplantation (BMT) models were used. Inboth, MoAb infusion markedly inhibited alloengraftment andhematopoietic recovery post-BMT. To determine if the adverse effects onlymphohematopoiesis in the allogeneic BMT recipients were caused by animmune or nonimmune mechanism, studies were performed in congenic BMTrecipients to preclude an immune mechanism as the cause for delayedrecovery post-BMT. MoAb infusion resulted in impairedlymphohematopoietic recovery in congenic BMT recipients and markedlyreduced day 12 colony-forming unit-spleen formation in syngeneic BMTrecipients, consistent with a nonimmune mediated mechanism. Because thespleen is a site of early hematopoietic recovery post-BMT, studies were performed using adult splenectomized syngeneic BMT recipients. MoAbinfusion delayed recovery in both nonsplenectomized and splenectomized recipients post-BMT, indicating that the delayed hematopoietic recoverywas not the consequence of an abnormal homing pattern of hematopoieticprogenitors to the spleen early post-BMT. CD48 MoAb was necessaryand sufficient for the inhibition of GVHD lethality and delayedlymphohematopoietic effects of the combined MoAb regimen. CD48 MoAbwas found to induce a profound modulation of CD48 antigen expression onBM cells, suggesting that the CD48 antigen may have an importantfunction in hematopoiesis in the BM compartment. Taken together, thesedata provide evidence that the CD48 antigen plays a critical role inregulating hematopoiesis in post-BMT.     

Release of nonesterified fatty acids during cerulein-induced pancreatitis in rats

During acute pancreatitis, data obtainedin vitro suggest that pancreatic lipase, acting on circulating or tissular triglycerides, might generate nonesterified fatty acids (NEFA) that could promote pancreatic and fat tissue necrosis. This work determined whether NEFA were actually producedin vivo in pancreatic tissue and in blood during cerulein-induced pancreatitis in rats. Intraperitoneal injections of cerulein induced pancreatitis. To promote the possible NEFA release by pancreatic lipase, a venous infusion of human very low density lipoprotein (VLDL) was used to cause hypertriglyceridemia. NEFA were measured in portal and aortic blood and in tissue extracts prepared from pancreas homogenates. NEFA did not increase either in peripheral or in portal blood. In pancreatic tissue, NEFA levels did not differ from controls. The major hypertriglyceridemia produced by human VLDL intravenous infusion neither altered the course of the disease nor promoted plasma NEFA release. The role commonly attributed to NEFA in acute pancreatitis seems questionable.Dr. Paye was the recipient of a scholarship from the Fondation pour la Recherche Médicale (Paris). Partial financial support of the work was provided by the Conseil Scientifique of Faculté X. Bichat and by Association Charles Debray.     

Informed consent for medical procedures: local and national practices

BACKGROUND: No studies have assessed whether clinicians obtain informed consent for invasive medical procedures, and there are no explicit national standards to guide the process. HYPOTHESIS: Informed consent practices are inconsistent for commonly performed invasive medical procedures. METHODS: A simple questionnaire was electronically mailed and/or faxed to training program directors of critical care medicine and internal medicine departments, and to ICU directors in the state of Connecticut. The questionnaire listed common invasive medical procedures and asked the respondents to check those for which practitioners routinely obtain informed consent in their hospital. RESULTS: The three samples, national intensivists (88 respondents), Connecticut intensivists (29 respondents), and national internists (56 respondents) demonstrated heterogeneity of consenting practices. The rate of obtaining consent for common vascular access procedures ranged from 20 to 90%. The rates of obtaining consent for Foley catheterization and nasogastric intubation were uniformly < 10%, and those for endoscopic procedures were > 90%. Separate consent (beyond the general consent to treat) was not uniformly obtained for the transfusion of blood products (range, 74 to 93%) and common diagnostic medical procedures (eg, thoracentesis, paracentesis, or lumbar puncture; range, 77 to 96%). Surgical intensivists reported that the obtaining of consent for invasive procedures was less routine compared to medical intensivists. Lower rates of consent were noted by those respondents who used a "blanket" consent form, which was signed at the time of hospital admission, to cover subsequent procedures. CONCLUSIONS: In this relatively small sample, there was no uniform practice of informed consent for commonly performed invasive medical procedures. Consent was routinely obtained for GI endoscopy, bronchoscopy, and medical research, and was not obtained for Foley catheterization and nasogastric intubation. The obtaining of consent for vascular cannulation and diagnostic procedures was not routine in the ICUs of a substantial number of respondents. Explicit standards that delineate specifically which procedures require consent may be required to assure more uniform practices.     

The rehabilitation of clinical assessment for the diagnosis of pulmonary embolism

Pulmonary angiography is the gold standard for diagnosis of segmental pulmonary embolism, but no longer for subsegmental pulmonary embolism because the inter-observer agreement for angiographically documented subsegmental pulmonary embolism is only 60%. A normal rapid ELISA VIDAS D-dimer test result and a normal perfusion scan exclude pulmonary embolism with a negative predictive value of >99%, irrespective of clinical score. The positive predictive value for pulmonary embolism of a high probability VP-scan compared to pulmonary angiography is 87% indicating that 13% of patients with a high probability VP-scan do not have pulmonary embolism. The combination of a negative CUS, a low clinical score, and a non-diagnostic VP-scan safely excludes pulmonary embolism. Patients with a non-diagnostic VP-scan, a negative CUS, but a moderate to high clinical score are candidates for pulmonary angiography. The positive predictive value of helical spiral CT is >95 to 99%. The combination of a negative CUS, a low clinical score, and the presence of a clear alternative diagnosis is predicted to safely exclude pulmonary embolism. Helical spiral CT detects all clinical relevant pulmonary emboli and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic or a high-probability VP-scan. The negative predictive value during 3 months followup after a negative spiral CT for pulmonary embolism in 4 retrospective studies and 1 prospective management study was >99%. Only a small group of patients (1-2%) with a non-diagnostic spiral CT are candidates for pulmonary angiography. Therefore, it is predicted that the spiral CT will replace both VP-scanning and pulmonary angiography to safely exclude or diagnose pulmonary emboli in patients with suspected pulmonary embolism.     

Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)     

Raynaud’s phenomenon in undifferentiated connective tissue disease (UCTD)

The aim of this study was to ascertain which clinical and immunological factors are associated with Raynauds phenomenon (RP) in patients with undifferentiated connective tissue disease (UCTD) and to investigate microvascular involvement. A total of 78 patients were evaluated. They all showed symptoms suggestive of a connective tissue disorder (CTD), but did not fulfil the criteria for any of the defined CTDs. They all had a disease duration of at least 1 year. Nailfold capillaroscopy (NC) was performed using a computerised videomicroscope. We diagnosed RP in 52.5% of our patients. Patients with RP showed a higher occurrence of oesophageal dysmotility (p=0.001) and anti-ribonucleoprotein (RNP) antibodies (p=0.004) than those without RP. The distinguishing capillaroscopic characteristics of UCTD patients with RP were widened and irregularly enlarged loops (75 and 55%, respectively), giant capillaries (35%), and less than two haemorrhages per finger (40%). The combination of features indicative of a slow scleroderma pattern was present in 18 of 40 patients with UCTD and RP (p=0.0003). Only 3 of the original 78 patients (3.8%) developed a definite CTD. In none of our patients did we observe avascular areas or changes from the original capillaroscopic pattern during follow-up examination. Our study indicates that patients with UCTD would seem to have a benign form of RP, since they show the absence of cutaneous complications, the existence of a mild microvascular damage and a stable nailfold capillary pattern. Further examinations of these patients will be required in order to confirm our findings.     

Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients

OBJECTIVES: We sought to assess the electromechanical parameters, using tissue Doppler echocardiography, as potential independent predictors of heart failure (HF) worsening. BACKGROUND: Ventricular conduction disorders worsen the prognosis for HF patients. However, the relationships between the QRS width and morphology, hemodynamic parameters, and presence and magnitude of intra-left ventricular (LV) and inter-ventricular (V) asynchrony have not been well clarified. METHOD: A total of 104 patients with an LV ejection fraction (EF) 相似文献