Clopidogrel attenuates coated-platelet production in patients undergoing elective coronary catheterization.

INTRODUCTION: Coated-platelets are a subclass of highly thrombotic activated platelets with an enhanced ability to generate thrombin. Excessive numbers of coated-platelets are believed to increase thrombotic risk. A previous report demonstrated that P2Y12 inhibition in vitro attenuates coated-platelet formation. The aim of this study was to determine the effect clopidogrel has on coated-platelet formation. METHODS AND RESULTS: We enrolled 27 patients undergoing elective coronary angiography. A total of 3 blood samples were taken from eligible patients: baseline, 24-hour postclopidogrel (preangiography), and 6-hour postangiography. Coated-platelet levels, expressed as percentage of total platelets, were determined with convulxin and thrombin with or without 1.5 or 6 microM adenosine diphosphate (ADP). Baseline levels of coated-platelets were 40.0% +/- 14.3% (mean +/- 1 SD). After clopidogrel exposure, the coated-platelet level was 32.8% +/- 13.6%, representing a significant 7.2% absolute reduction (AR) (17.8% relative reduction (RR); P < 0.0001). Clopidogrel significantly lowered the convulxin, thrombin plus ADP coated-platelet production (11.0% AR; 20.1% RR for 1.5 microM and 11.2% AR; 19.1% RR for 6 microM). CONCLUSIONS: This is the first report on the impact of in vivo administration of a P2Y12 antagonist on coated-platelet formation. The significance of a partial attenuation in coated-platelet potential has yet to be determined, but this could represent a new antithrombotic mechanism of clopidogrel beyond inhibition of ADP-induced aggregation.

Angiotensin-converting enzyme gene polymorphism in a cohort of coronary angiography patients.

An association between a polymorphism of the angiotensin-converting enzyme (ACE) gene and myocardial infarction (MI) in men has been previously reported. The present study examines the association between ACE genotype, atherosclerosis, MI, hypertension and other cardiovascular risk factors in Caucasian men (n=576) and women (n=124) who have undergone coronary angiography. Gene frequencies are also reported for African-American men (n=56). Genotype determination was based on the presence (allele I) or absence (allele D) of a 287 nucleotide Alu sequence in intron 16 of the ACE gene. Genotype frequencies for DD, ID and II were: 30.9, 47.7, 21.4% for Caucasian men; 28.2, 48.4, 23.4% for Caucasian women; and 30.4, 46.4, 23.2% for African-American men. There were no statistically significant associations between ACE genotype and number of plaques (> or =10% obstruction), lipid variables, or body mass index (BMI) for Caucasian men. Caucasian women with the DD genotype had on average fewer plaques, but this was accounted for by their younger ages. In Caucasian males, the DD genotype independently contributed to the presence of hypertension (odds ratio=1.8, 95% CI 1.1-2.9) after adjusting for age and BMI. In Caucasian males with total cholesterol levels less than 200 mg/dl (n=237), the DD (odds ratio=2.5, 95% CI 1.2-5.4) and ID genotypes (odds ratio=2.2, 95% CI 1.1-4.4) were associated with a history of MI.

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts.

BACKGROUND: Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. METHODS: We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had >/=60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. RESULTS: Median percent diameter stenosis improved from 69% to 45% (P =.0001) after local delivery, and TIMI thrombus grade >/=1 incidence reduced from 68% to 34% (P =.0001). TIMI flow grade was not significantly affected (P =.12). All patients had a successful intervention (

Predictions of coronary artery stenosis by artificial neural network.

Data from angiography patient records comprised 14 input variables of a neural network. Outcomes (coronary artery stenosis or none) formed both supervisory and output variables. The network was trained by backpropagation on 332 records, optimized on 331 subsequent records, and tested on final 100 records. If 0.40 was chosen as the output distinguishing stenosis from no stenosis, 81 patients who had stenosis would have been identified, while 9 of 19 patients who did not have stenosis might have been spared angiography. The results demonstrated that artificial neural networks could identify some patients who do not need coronary angiography.

Safety and efficacy of abciximab use in conjunction with intracoronary urokinase in patients requiring angioplasty.

Abciximab decreases ischemic complications during angioplasty. Intracoronary urokinase lyses intracoronary thrombus. We studied the combination of both drugs. Twenty-six consecutive patients with acute coronary syndromes and intracoronary thrombus underwent intervention with abciximab and intracoronary urokinase. All received aspirin and IV heparin. The dose of abciximab was a weight-adjusted bolus and a 12-hr infusion. The dose of urokinase was 250,000 to 633,000 units. Hemorrhagic complications were classified according to the TIMI study group. Hemoglobin and platelet counts were measured before and 12 and 48 hr after the procedure. Procedural success was achieved in 24 patients. There were no deaths or repeat interventions. No patient had a major bleeding complication. Only two had minor complications. One patient needed blood transfusion. None had a stroke or thrombocytopenia. The use of abciximab and intracoronary urokinase in the presence of intracoronary thrombus is associated with encouraging efficacy and few complications. Cathet. Cardiovasc. Intervent. 49:113-116, 2000.

Industry, occupation, and disability insurance beneficiary work return.

This article uses the New Beneficiary Data System to describe the first job held after award of Disability Insurance benefits, in terms of occupation and industry. It examines work activity within sectors of employment, and looks at the issues of whether work return in certain industries and occupations varies according to the demographic characteristics of the beneficiaries. The article also presents data on sector-specific employer accommodations that can aid in sustained work return. Postentitlement work was fairly evenly distributed across occupational and industrial sectors. Persons with higher levels of educational attainment were found to be in white-collar employment sectors. There were noticeable differences in the availability of employer accommodations across postentitlement occupations and industries.

Low- versus high-dose recombinant urokinase for the treatment of chronic saphenous vein graft occlusion.

Recanalization of a totally occluded saphenous vein graft (SVG) using commercially available urokinase from human kidney cells has been shown to be effective, but the duration of infusion and complications such as allergic reactions, bleeding events, and non-Q-wave myocardial infarction have limited its acceptance. Recently, genetic engineering has allowed the synthesis of recombinant urokinase (r-UK). Patients with an occluded SVG from 37 centers were randomized to receive a 6-hour infusion of either low-dose (125,000 IU/hour) or high-dose (350,000 IU/hour) r-UK followed by up to a maximum of 18 hours of r-UK (125,000 IU/hour) via a subselective catheter directly into the occluded vein graft. The primary study end point was final preintervention achievement of Thrombolysis In Myocardial Infarction (TIMI) flow > or = 2 using core angiographic analysis. One hundred seven patients were randomized and 98 received the study drug (low dose 52 patients, high dose 46 patients). TIMI flow > or = 2 after completion of the study drug was higher in the high-dose group (51% vs 24%, p = 0.019). This difference narrowed, but a trend was still evident on the final angiogram after adjunctive mechanical intervention (72% vs 58%, p = 0.254). Bleeding complications were frequent; severe or life-threatening bleeding occurred in 12% of patients on the low dose and 11% of patients on the high dose (p = NS), including 2 intracerebral bleeds, both of which were fatal with 1 in each group. Thus, in patients with an occluded SVG, a randomized trial of direct low-dose versus high-dose r-UK infusion demonstrated increased recanalization rates (TIMI flow > or = 2) in the high-dose arm. Percutaneous revascularization of SVG with r-UK can be accomplished with acceptable success rates, but complications are frequent.

Plasma immunoglobulins in patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess immunoglobulin (Ig) concentrations in plasma and ascitic fluid of patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Tertiary medical center. PATIENT(S): Ten patients with severe OHSS after ovulation induction for IVF and 10 controls who had undergone similar ovulation induction and did not develop OHSS. INTERVENTION(S): Three blood samples were obtained from each OHSS patient: one at the time of hospitalization for severe OHSS, one when significant clinical improvement was evident, and one at the first follow-up visit after discharge from the hospital. Blood samples were drawn from control patients 6-8 days after ET. Ascitic fluid was obtained from all patients with OHSS by therapeutic paracentesis. MAIN OUTCOME MEASURE(S): Immunoglobulin concentrations were assayed by radial immunodiffusion. RESULT(S): Significantly lower levels of gamma-globulins, specifically IgG and IgA, were detected in the plasma of patients with severe OHSS, whereas alpha- and beta-globulin levels as well as IgM levels were not significantly different from those in controls. Both IgG and IgA levels increased as patients clinically improved. Ascitic fluid contained high IgG, moderate IgA, and negligible IgM levels. CONCLUSION: Severe OHSS is characterized by hypogammaglobulinemia, attributed to leakage of medium-molecular-weight immunoglobulins such as IgG and IgA to the peritoneal cavity.

Primary stent implantation for acute myocardial infarction during pregnancy: use of abciximab, ticlopidine, and aspirin.

Recent evidence suggests that coronary stenting and the use of antiplatelet agents during coronary interventions will improve the outcome of patients with acute myocardial infarction (AMI). We describe the management of AMI in a 30-year-old woman, 38 weeks pregnant, with primary stenting and antiplatelet agents.

Role of factor V Leiden mutation in patients with angiographically demonstrated coronary artery disease.

The study sought to determine whether coagulation factor V Leiden (FV Leiden) plays a role in the pathogenesis of coronary artery disease and/or myocardial infarction. Association of FV Leiden with venous thromboembolism is well established in the literature, but the role of the mutation in arterial thrombotic events is controversial. Some studies have documented an association between the mutation and myocardial infarction and stroke in juveniles. Few studies have explored its possible contribution to coronary atherosclerosis. We screened FV genotype in 850 predominantly white coronary angiography patients. Coronary artery disease risk factors and history of myocardial infarction were then analyzed by genotype. The FV Leiden mutation occurred in 54 (6.4%) patients. There was one homozygote; a 37-year-old, white male smoker with a history of myocardial infarction. Gene frequencies for white males and females were similar: 0.965 for the normal allele and 0.035 for FV Leiden. Gene frequencies for both genders were in Hardy-Weinberg equilibrium. FV Leiden was not a useful predictor (p=0.23) of the presence of clinically defined atherosclerosis (> or = 50% stenosis) in a logistic regression model adjusting for age, lipoprotein (a), total cholesterol, triglycerides, high density lipoprotein cholesterol, and fibrinogen. In addition, there was no difference in frequency of FV Leiden among those with and without medical histories of myocardial infarction (p=0.51). Allelic frequencies of FV Leiden in this patient group do not differ significantly from those reported for white populations. The FV Leiden mutation in its heterozygous state is not independently associated with coronary artery disease or myocardial infarction.

Long-term angiographic follow-up of occluded saphenous bypass grafts treated with prolonged urokinase infusion.

We report on 10 occluded saphenous vein bypass grafts in nine patients treated with prolonged urokinase infusion. Our purpose was to evaluate the patency of these grafts during long-term follow-up. We retrospectively analyzed consecutive patients treated at a single center. All patients had angiography 0.25 to 54 months after treatment. Results indicated that clot lysis was achieved in all grafts with urokinase infusions of 1,790,000 to 25,920,000 units given over 17 to 108 hours. In two grafts there was no filling of the distal native vessel and in one, a 50% stenosis with ulceration remained. There was a progressive loss of graft patency over the first 18 months, but 50% of the grafts that were opened with prolonged urokinase infusion remain patent. Long-term patency depends upon successful opening without residual obstruction and with good flow into the distal native vessel.

Iron measures in coronary angiography patients.

Excess iron has been postulated as a risk factor for coronary artery disease (CAD) because of its presence in atherosclerotic lesions, its ability to oxidize low density lipoprotein cholesterol (LDLc), and its promotion of oxygen reperfusion damage after an ischemic event. Whether iron, indirectly measured by its storage protein ferritin and its transport protein transferrin, is related to CAD was examined in a consecutive series of white male (n = 457) and female (n = 114) cardiac patients. Atherosclerosis measures were analyzed in patients grouped by tertiles of ferritin. A similar analysis was done with tertiles of transferrin. Contrary to expectations, men in the third tertile of ferritin had a smaller mean number of stenoses than men in the two lower tertiles (4.9 versus 5.6 and 5.9; P = 0.027); otherwise, there were no statistically significant differences in either number of lesions or extent of arterial narrowing based on tertiles of either measure. Separate multiple logistic regression models with age, fibrinogen, LDLc and triglycerides as covariates provided no evidence that ferritin (odds ratio = 0.88 with 95% C.I. = 0.72-1.07 for men and odds ratio = 0.79 with 95% C.I. = 0.54-1.16 for women) or transferrin (odds ratio = 0.60 with 95% C.I. = 0.31-1.16 for men and odds ratio = 1.33 with 95% C.I. 0.52-3.42 for women) were important correlates of the presence of atherosclerosis in this study.

Activated factor VII levels in patients with angiographically confirmed coronary artery disease.

We have examined factor VIIa levels in consecutive consenting patients undergoing coronary angiography (n = 702) to determine if levels are related to the presence of coronary arterial narrowing and to the degree and extent of that narrowing. Both men and women with clinically defined coronary artery disease (> or = 50% stenosis in at least 1 vessel) had factor VIIa levels that were similar to men and women with less stenosis or normal coronary arteries.

Work while receiving disability insurance benefits: additional findings from the New Beneficiary Followup Survey.

From the foregoing analyses, the following picture emerges about persons who work after award of DI benefits: Almost one-quarter of the sample population attempted to reenter the labor force in the 10-year NBS-NBF period. The higher the level of education, the greater the proportion of persons who worked. Younger beneficiaries were more likely to work than older beneficiaries. About half of the beneficiaries who worked did so on a full-time (40-hour-or-more per week) basis. Most beneficiaries worked because of financial need. The profile of reasons for working did not vary across demographic groups and aspects of the first job held. Most beneficiaries began working without attributing this decision to an improvement in their health. Individuals pursued different methods of job search. No single approach emerged as the most successful. Job search modes did not vary for different groups and different jobs. Four activities were most likely to lead to job offers: persons checking where they had worked before, asking a friend, answering an ad, and following up a vocational rehabilitation lead. These findings were not conclusive because small numbers of persons engaged in these activities. Thirty percent of DI workers returned to their preentitlement employer. The beneficiaries' first postentitlement jobs had less exertion, fewer hours, and lower pay than did their job held prior to award. The likelihood of working was the same across a broad range of disabling health conditions. In terms of work return policy, formal work return programs aimed at young beneficiaries and those with higher levels of educational attainment would produce the greatest number of job placements. It appears that no targeting of programs is necessary along gender lines. The anomalous finding of an absence of the relationship between improvement in health and labor-force reentry requires further investigation. Any followup in this area of inquiry should plan to have the data collected close to the time of postentitlement job entry.

Fibrinogen levels in women having coronary angiography.

Fibrinogen has emerged as a risk factor for coronary artery disease in men that equals cholesterol in importance. It is known to play an important role in reparative processes, and evidence is accumulating that fibrinogen/fibrin accumulates at the site of minimal vascular injury. Fibrinogen contributes significantly to blood viscosity and its adherence to endothelium may mediate progression of atheromatous lesions. This study was designed to examine a number of markers of risk in a consecutive series of cardiology patients undergoing coronary catheterizations over a 15-month period. This article examines the level of fibrinogen in relation to the number of reported coronary stenoses and disease severity in a series of Caucasian female patients (n = 101). Women were classified as diseased if they had at least 1 lesion > or = 25% in the coronary anatomy and nondiseased if they had no lesions > or = 25%. The number of reported lesions correlates significantly with fibrinogen levels (r = 0.36, p = 0.0002). Women with fibrinogen levels > or = 283 mg/dl had a 3.2-fold increased risk (95% confidence interval 1.2 to 9.1) of having at least 1 stenosis > or = 25% after adjusting for age and diabetic status. Smoking and body mass index did not differ by disease status and thus did not confound the finding. Mean fibrinogen levels showed a progressive positive association with increasing clinically defined vessel involvement (stenosis > or = 50%).

Prostate specific antigen is metabolized in the liver.

PURPOSE: The site of metabolism of prostate specific antigen (PSA) was determined. MATERIALS AND METHODS: In a prospective study, during clinically indicated left and right heart catheterizations for various cardiac diseases in 12 men (mean age 62.5 +/- 8.3 years, standard deviation), selective blood samples were obtained from the infra-renal, infra-hepatic and supra-hepatic inferior vena cava, renal vein, superior vena cava, pulmonary artery and femoral artery. Mean PSA concentration was calculated for all vascular sites. Using a paired Student t test, the mean difference between the afferent and efferent PSA concentrations across the renal, hepatic, pulmonary and pelvic circulation was calculated. RESULTS: The hepatic gradient between the infra-hepatic and suprahepatic inferior vena cava showed the greatest decrease (0.11 +/- 0.16 ng./ml. or 8.3%) in PSA concentration and was statistically significant (p = 0.04). A smaller decrease across the pulmonary circulation was statistically insignificant. No decrease in the PSA concentration was noted across the renal circulation. The PSA concentration increased significantly (0.19 +/- 0.18 ng./ml. or 16.3%, p = 0.003) across the pelvic circulation, confirming the release of PSA from the prostate. CONCLUSIONS: PSA is released from the prostate. The kidneys and lungs do not have a significant role in elimination of PSA, and the liver appears to be the most likely site of its metabolism. Although our sample size is small and the PSA range is narrow, our results strongly support these conclusions.

Characterization of the cspB gene encoding PS2, an ordered surface-layer protein in Corynebacterium glutamicum.

PS2 is one of two major proteins detected in the culture media of various Corynebacterium glutamicum strains. The coding and promoter regions of the cspB gene encoding PS2 were cloned in lambda gt11 using polyclonal antibodies raised against PS2 for screening. Expression of the cspB gene in Escherichia coli led to the production of a major anti-PS2 labelled peptide of 63,000 Da, corresponding presumably to the mature form of PS2. It was detected in the cytoplasm, periplasm and surrounding medium of E. coli. Three other slower migrating bands of 65,000 68,000 and 72,000 Da were detected. The largest one probably corresponds to the precursor form of PS2 in E. coli. Analysis of the nucleotide sequence revealed an open reading frame (ORF) of 1533 nucleotides. The deduced 510-amino-acid polypeptide had a calculated molecular mass of 55,426 Da. According to the predicted amino acid sequence, PS2 is synthesized with a N-terminal segment of 30-amino-acid residues reminiscent of eukaryotic and prokaryotic signal peptides, and a hydrophobic domain of 21 residues near the C-terminus. Although no significant homologies were found with other proteins, it appears that some characteristics and the amino acid composition of PS2 share several common features with surface-layer proteins. The cspB gene was then disrupted in C. glutamicum by gene replacement. Freeze-etching electron microscopy performed on the wild-type strain indicated that the cell wall of C. glutamicum is covered with an ordered surface of proteins (surface layer, S-layer) which is in very close contact with other cell-wall components. These structures are absent from the cspB-disrupted strain but are present after reintroduction of the cspB gene on a plasmid into this mutant. Thus we demonstrate that the S-layer protein is the product of the cspB gene.

Cloning and nucleotide sequence of the csp1 gene encoding PS1, one of the two major secreted proteins of Corynebacterium glutamicum: the deduced N-terminal region of PS1 is similar to the Mycobacterium antigen 85 complex.

Two proteins, PS1 and PS2, were detected in the culture medium of Corynebacterium glutamicum and are the major proteins secreted by this bacterium. No enzymatic activity was identified for either of the two proteins. Immunologically cross-reacting proteins were found in a variety of C. glutamicum strains but not in the coryneform Arthrobacter aureus. The gene encoding PS1, csp1, was cloned in lambda gt11 using polyclonal antibodies raised against PS1 to screen for producing clones. The csp1 gene was expressed in Escherichia coli, presumably from its own promoter, and directed the synthesis of two proteins recognized by anti-PS1 antibodies. The major protein band, of lower M(r), was detected in the periplasmic fraction. It had the same M(r) as the PS1 protein band detected in the supernatant of C. glutamicum cultures and presumably corresponds to the mature form of PS1. The minor protein band appears to be the precursor form of PS1. The nucleotide sequence of the csp1 gene was determined and contained an open reading frame encoding a polypeptide with a calculated molecular weight of 70,874, with a putative signal peptide with a molecular weight of 4411. This is consistent with the M(r) determined for PS1 from C. glutamicum culture supernatant and E. coli whole-cell extracts. The NH2-half of the deduced amino acid is similar (about 33% identical residues and 52% including similar residues) to the secreted antigen 85 protein complex of Mycobacterium. The csp1 gene in C. glutamicum was disrupted without any apparent effect on growth or viability.

Complete block below the His bundle induced by left-sided cardiac catheterization.

A patient with right bundle branch block and left anterior fascicular block developed complete heart block during passage of a catheter into the left ventricle. Intracardiac electrograms showed the block to be in the distal His-Purkinje system. The block resolved without complications.

Electrocardiographic abnormalities during ritodrine administration.

Electrocardiographic abnormalities have been reported during ritodrine tocolysis. No previous studies, however, have included controls. The purpose of this study is to evaluate the electrocardiographic tracings of patients receiving ritodrine tocolysis and compare them with those of matched controls. Holter monitors were placed on eight patients receiving ritodrine tocolysis and eight control patients for 24 hours to make continuous electrocardiographic records. Twelve-lead electrocardiograms, serum glucose, and electrolyte concentrations were monitored serially in all patients. Four of the eight patients receiving ritodrine tocolysis demonstrated ST segment depression, while none of the control patients manifested any electrocardiographic abnormalities. The observed ST segment depression appears to be related to the degree of maternal tachycardia and the level of hypokalemia and hyperglycemia that occurs during early ritodrine tocolysis.