Metabolic Signaling and Spatial Interactions in the Oral Polymicrobial Community.

Oral supra- and subgingival biofilms are complex communities in which hundreds of bacteria, viruses, and fungi reside and interact. In these social environments, microbes compete and cooperate for resources, such as living space and nutrients. The metabolic activities of bacteria can transform their microenvironment and dynamically influence the fitness and growth of cohabitating organisms. Biofilm communities are temporally and spatially organized largely due to cell-to-cell communication, which promotes synergistic interactions. Metabolic interactions maintain biofilm homeostasis through mutualistic cross-feeding, metabolic syntrophy, and cross-respiration. These interactions include reciprocal metabolite exchanges that promote the growth of physiologically compatible bacteria, processive catabolism of complex substrates, and unidirectional interactions that are globally important for the polymicrobial community. Additionally, oral bacterial interactions can lead to detoxification of oxidative compounds, which will provide protection to the community at large. It has also been established that specific organisms provide terminal electron acceptors to partner species that result in a shift from fermentation to respiration, thus increasing ATP yields and improving fitness. Indeed, many interspecies relationships are multidimensional, and the net outcome can be spatially and temporally dependent. Cross-kingdom interactions also occur as oral yeast are antagonistic to some oral bacteria, while numerous mutualistic interactions contribute to yeast-bacterial colonization, fitness in the oral community, and the pathogenesis of caries. Consideration of this social environment reveals behaviors and phenotypes that are not apparent through the study of microbes in isolation. Here, we provide a comprehensive overview of the metabolic interactions that shape the oral microbial community.

Avoidance learning and classical eyeblink conditioning as model systems to explore a learning diathesis model of PTSD.

Experiencing a trauma is necessary, but not sufficient, for the development of post-traumatic stress disorder (PTSD) in that most individuals who experience a trauma do not go on to develop PTSD. This suggests that identifiable vulnerabilities (i.e., diatheses) exist that increase the risk for the development of PTSD. One such factor is the personality temperament of behavioral inhibition (BI). Organisms that exhibit BI were studied in the context of avoidance learning and classical eyeblink conditioning. We present a body of evidence supporting a learning diathesis model in which behaviorally inhibited organisms exhibit enhanced acquisition and resistance to extinction in these tasks. Vulnerable individuals show learning-related enhancements when the learning situation involves some degree of uncertainty. We review the known brain circuitry involved in classical eyeblink conditioning in the context of the learning diathesis model. Finally, the data reviewed here demonstrate the value of studying vulnerability factors in humans and a rodent model using cerebellar-dependent learning tasks for understanding the acquisition and endurance of PTSD symptomatology.

Plasminogen binding and degradation by Treponema denticola: Identification of the plasminogen binding interface on the FhbB protein.

Treponema denticola is a proteolytic-anaerobic spirochete whose abundance in the subgingival crevice correlates with periodontal disease severity. Treponema denticola evades serum-mediated killing through the binding of factor H (FH), a negative regulator of the complement system. The T. denticolaFH receptor has been identified as FhbB, an 11.4kDa immunodominant lipoprotein. Three distinct subfamilies of FhbB proteins have been delineated and designated as FhbB1, FhbB2 and FhbB3. In this study we demonstrate that all FhbB variants bind human plasminogen (Plg). Competitive binding analyses revealed that FH and Plg do not compete for binding. Binding studies with FhbB135405 site-directed amino acid substitution mutants demonstrated that the interaction domains for FH and Plg on FhbB are separable. Inhibition of Plg-FhbB binding by ε-aminocaproic acid (a lysine analog) indicates that binding is mediated by electrostatic interactions that presumably occur with Lys binding sites contained within Plg "Kringle" domains 1, 2, 4 or 5. Similar to that demonstrated for FH, Plg can also serve as a substrate for the T. denticola protease, dentilisin. The in vivo consequences of dentilisin-mediated cleavage of Plg remained to be determined. The data presented demonstrate that FhbB is a multi-functional protein that may contribute to virulence through several mechanisms including immune evasion, manipulation of the host immune response, adherence or tissue invasion.

Transcriptome analysis of Porphyromonas gingivalis and Acinetobacter baumannii in polymicrobial communities.

Acinetobacter baumannii is a nosocomial, opportunistic pathogen that causes several serious conditions including meningitis, septicemia, endocarditis, and pneumonia. It can be found in the oral biofilm, which may be a reservoir for pneumonia and chronic obstructive pulmonary disease. Subgingival colonization by A. baumannii is associated with chronic and aggressive periodontitis as well as refractory periodontal disease. Porphyromonas gingivalis, a keystone periodontal pathogen localized to subgingival plaque, is also implicated in several chronic conditions including aspiration pneumonia. Although both bacteria are found together in subgingival plaque and can cause multiple polymicrobial infections, nothing is known about the interactions between these two important human pathogens. In this study, we used RNA sequencing to understand the transcriptional response of both species as they adapt to heterotypic communities. Among the differentially regulated genes were those encoding a number of important virulence factors for both species including adhesion, biofilm formation, and protein secretion. Additionally, the presence of A. baumannii increased the abundance of P. gingivalis in model dual-species communities. Collectively these results suggest that both P. gingivalis and A. baumannii adapt to each other and have synergistic potential for increased pathogenicity. In identifying the mechanisms that promote pathogenicity and refractory disease, novel approaches to mitigate polymicrobial synergistic interactions may be developed to treat or prevent associated diseases.

Structure-function aspects of the Porphyromonas gingivalis tyrosine kinase Ptk1.

The development of synergistically pathogenic communities of Porphyromonas gingivalis and Streptococcus gordonii is controlled by a tyrosine-phosphorylation-dependent signaling pathway in P. gingivalis. The Ptk1 bacterial tyrosine (BY) kinase of P. gingivalis is required for maximal community development and for the production of extracellular polysaccharide. We show that the consensus BY kinase Walker A and B domains, the RK cluster, and the YC domain of Ptk1 are necessary for autophosphorylation and for substrate phosphorylation. Mass spectrometry showed that six tyrosine residues in a 16-amino-acid C-terminal region were phosphorylated in recombinant (r) Ptk1. Complementation of a ptk1 mutant with the wild-type ptk1 allele in trans restored community development between P. gingivalis and S. gordonii, and extracellular polysaccharide production by P. gingivalis. In contrast, complementation of Δptk1 with ptk1 containing a mutation in the Walker A domain failed to restore community development or extracellular polysaccharide production. rPtk1 was capable of phosphorylating the tyrosine phosphatase Ltp1 and the transcriptional regulator CdhR, both of which are involved in the development of P. gingivalis communities with S. gordonii.

Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma.

Traditionally, non-small cell lung cancer (NSCLC) has been evaluated as a unique entity in genotyping studies. However, recent biological data suggest that different NSCLC subtypes, specifically adenocarcinomas (AC) and squamous cell carcinomas (SCC), differentially alter cancer behavior. Several studies have associated a p53 polymorphism at codon 72 with NSCLC susceptibility. This study investigated whether different p53 genotypes altered the overall risk of developing AC versus SCC. Polymorphisms in metabolizing enzymes, together with prolonged exposure to tobacco carcinogens, can result in accumulation of DNA damage; these effects may potentiate the effects of subtle differences in p53 function. Thus, interactions between polymorphisms of p53 and either GSTM1 or GSTT1 were also evaluated. We analyzed 1168 incident lung cancer cases and 1256 control subjects using multiple logistic regression. Histological data were available for 1144 cases (98%): 585 with AC, 284 with SCC, and 275 with other histological subtypes (large cell, small cell, mixed, and other). An increase in the NSCLC risk posed by the p53 Pro allele (versus Arg/Arg) was seen in AC compared with controls [adjusted odds ratio (OR), 1.36; 95% confidence interval (CI), 1.1-1.7] but not in SCC (adjusted OR, 1.04; 95% CI, 0.8-1.4). Among AC and SCC cancer patients, individuals with the GSTM1-null genotype had an OR of 1.80 (95% CI, 1.1-2.8; case-only analysis) of having AC versus SCC if they also carried a p53 Pro allele. We conclude that different genotype combinations of p53 and GSTM1 increase the risk of developing specific histological subtypes of NSCLC.

The relationship between periprocedural myocardial infarction and subsequent target vessel revascularization following percutaneous coronary revascularization: insights from the EPIC trial. Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications.

OBJECTIVES: We sought to determine whether periprocedural myocardial infarction complicating percutaneous coronary revascularization is associated with subsequent clinical restenosis, as judged by the need for target vessel revascularization. BACKGROUND: Although myocardial enzyme elevation following angioplasty is associated with increased late mortality, its effect on subsequent clinical restenosis, as assessed by the need for late target vessel revascularization (TVR), is unknown. METHODS: Serial myocardial enzyme determinations were performed on 2,099 patients who underwent angioplasty or atherectomy in the Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial. Thirty-day survivors were prospectively followed for three years for adverse clinical events including death and need for TVR. RESULTS: Within the study population, periprocedural creatine kinase (CK) elevation was a predictor of late mortality. Among patients with elevated CK, however, a paradoxical decrease in the need for late TVR was present. This relationship became progressively more profound as the magnitude of CK release increased. Late TVR occurred in 29.8% of patients with no CK elevation, 24.8% with CK elevation to >3 times normal, and 16.9% with >10 times elevation (hazard ratio 0.51, 95% CI 0.29, 0.91). CONCLUSIONS: In the EPIC study, patients with periprocedural MI were less likely to develop clinical restenosis as measured by the need for TVR. Mechanistically, although it is unlikely that CK elevation prevents vascular renarrowing per se, myocardial necrosis impairs the clinical manifestation of restenosis, thereby reducing the need for ischemia-driven TVR. This novel finding 1) highlights the potential discordance between angiographic and clinical measures of restenosis, and 2) has implications for clinical trials, as therapies that reduce periprocedural MI may be associated with a perceived excess of restenosis when measured by the need for TVR.

Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. BACKGROUND: Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. METHODS: We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. RESULTS: Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non-insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p < 0.001). Mortality was lowest among those with diabetes receiving accelerated t-PA, which is consistent with the results of the overall patient cohort. Although stroke occurred more frequently among diabetic (1.9%) than nondiabetic patients (1.4%, p < 0.001), there was no significant difference in the rates of intracranial hemorrhage. Cardiac failure, shock, atrioventricular block and atrial flutter/ fibrillation were more common among diabetic patients. The proportion of patients undergoing revascularization was similar between patients with and without diabetes, although diabetic patients were more likely to undergo coronary artery bypass graft surgery (10.4% vs. 8.3%). Diabetes remained an independent predictor for mortality at 1-year follow-up (14.5% vs. 8.9%, p < 0.001). CONCLUSIONS: Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction.

Cost of cardiac care in the three years after coronary catheterization in a contained care system: critical determinants and implications.

OBJECTIVES: We sought to determine the clinical, angiographic, treatment and outcome correlates of the intermediate-term cost of caring for patients with suspected coronary artery disease (CAD). BACKGROUND: To adequately predict medical costs and to compare different treatment and cost reduction strategies, the determinants of cost must be understood. However, little is known about the correlates of costs of treatment of CAD in heterogeneous patient populations that typify clinical practice. METHODS: From a consecutive series of 781 patients undergoing cardiac catheterization in 1992 to 1994, we analyzed 44 variables as potential correlates of total (direct and indirect) in-hospital, 12- and 36-month cardiac costs. RESULTS: Mean (+/-SD) patient age was 65+/-10 years; 71% were men, and 45% had multiple vessel disease. The initial treatment strategy was medical therapy alone in 47% of patients, percutaneous intervention (PI) in 30% and coronary artery bypass graft surgery (CABG) in 24%. The 36-month survival and event-free (death, infarction, CABG, PI) survival rates were 89.6+/-0.2% and 68.4+/-0.4%, respectively. Median hospital and 36-month costs were $8,301 and $28,054, respectively, but the interquartile ranges for both were wide and skewed. Models for log(e) costs were superior to those for actual costs. The variances accounted for by the all-inclusive models of in-hospital, 12- and 36-month costs were 57%, 60% and 71%, respectively. Baseline cardiac variables accounted for 38% of the explained in-hospital costs, whereas in-hospital treatment and complication variables accounted for 53% of the actual costs. Noncardiac variables accounted for only 9% of the explained costs. Over time, complications (e.g., late hospital admission, PI, CABG) and drug use to prevent complications of heart transplantation became more important, but many baseline cardiac variables retained their importance. CONCLUSIONS: 1) Variables readily available from a comprehensive cardiovascular database explained 57% to 71% of cardiac costs from a hospital perspective over 3 years of care; 2) the initial revascularization strategy was a key determinant of in-hospital costs, but over 3 years, the initial treatment become somewhat less important, and late complications became more important determinants of costs.

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications.

OBJECTIVES: We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation. BACKGROUND: The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related. METHODS: The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation. RESULTS: Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 +/- 2.5 (mean +/- SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022). CONCLUSIONS: Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.

Acute myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics and outcome in the thrombolytic era. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the outcome of patients with acute myocardial infarction (MI) and bundle branch block in the thrombolytic era. BACKGROUND: Studies of patients with acute MI and bundle branch block have reported high mortality rates and poor overall prognosis. METHODS: The North American population with acute MI and bundle branch block enrolled in the Global Utilization of Streptokinase and t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial was matched by age and Killip class with an equal number of GUSTO-I patients without conduction defects. RESULTS: Of all 26,003 North American patients in GUSTO-I, 420 (1.6%) had left (n = 131) or right (n = 289) bundle branch block. These patients had higher 30-day mortality rates than matched control subjects (18% vs. 11%, p = 0.003, odds ratio [OR] 1.8) and were more likely to experience cardiogenic shock (19% vs. 11%, p = 0.008, OR 1.78) or atrioventricular block/asystole (30% vs. 19%, p < 0.012, OR 1.57) and to require ventricular pacing (18% vs. 11%, p = 0.006, OR 1.73). Bundle branch block also carried an independent 53% higher risk for 30-day mortality. Thirty-day mortality rates for patients with complete, partial and no reversion of the bundle branch block were 8%, 12% and 20%, respectively (two-tailed chi-square test for trend 5.61, p = 0.02, OR 0.34 for complete reversion, OR 0.55 for partial reversion). CONCLUSIONS: Bundle branch block at hospital admission in patients with acute MI predicts in-hospital complications and poor short-term survival.

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI. BACKGROUND: Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation. METHODS: In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves. RESULTS: A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; p = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab. CONCLUSIONS: The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.

Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis.

Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.

The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer.

Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CI), 0.74-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28). When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P = 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers.

The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior.

We conducted a hospital-based case-control study of 814 lung cancer patients and 1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphism with lung cancer susceptibility. Using PCR-RFLP genotyping assay techniques, we analyzed DNA samples to detect the variant forms of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and smoking behavior using generalized additive modeling. We found no overall association between NQO1 genotypes and lung cancer susceptibility, regardless of age, gender, family history of cancer, or histological cell type. However, our data demonstrated that in both former and current smokers, there was an association between NQO1 genotypes and lung cancer susceptibility that was dependent upon cigarette smoking duration and smoking intensity. For both current and former smokers, smoking intensity was more important in predicting cancer risk than smoking duration for all of the genotypes. Among former smokers, individuals with the T/T genotype were predicted to have a greater cancer risk than those with the C/C genotype for smoking durations up to 37 years. The predicted cancer risk for former smokers with the C/T versus T/T genotype depended on both smoking intensity and smoking duration. Our results support the concept that differential susceptibility to lung cancer is a function of both an inheritable trait in NQO1 metabolism and individual smoking characteristics.

The potential size of the hospitalist workforce in the United States.

PURPOSE: In the United States, there are currently 1,000 to 2,000 physicians who specialize in inpatient hospital care. The number of such hospitatists appears to be growing rapidly, but the ultimate size of the hospitalist workforce is not known. METHODS: We obtained workload data from 365 practicing hospitalists who completed a survey by the National Association of Inpatient Physicians. We then estimated the number of potential hospitalists, based on published national hospital census data. We assumed that hospitalists would care for all medical inpatients, but only at hospitals large enough to require > or = 3 hospitalists. We also made estimates based on the primary care physician referral base and international benchmarks. We estimated hospitalists' primary care referral base from telephone interviews with key informants. Official sources in England and Germany provided international workforce data. RESULTS: Hospitalists reported an average workload of 13 inpatients. To cover all adult medical inpatients in the United States, we estimate a potential workforce of 19,000 hospitalists. Sensitivity analysis yielded 10,000 to 30,000 hospitalists. Our alternative models yielded estimates within this same range. CONCLUSIONS: The future hospitalist workforce is potentially quite large. This finding highlights the need to evaluate the economic and clinical outcomes of hospitalist systems.

Inability of serum myocyte death markers to predict acute cardiac allograft rejection.

Acute cardiac rejection involves myocyte necrosis. Hence, markers of myocyte death may be useful in diagnosing rejection. Creatine kinase MB, MB isoforms, and troponins I and T were measured in 186 patients undergoing 365 endomyocardial biopsies. No differences were noted with rejection (rejectors vs. nonrejectors: CK=63.8 U/L and 86.6 U/L, P=0.0881; CK MB=2.04 ng/ml and 2.06 ng/ml, P=0.949; troponin T=0.134 ng/ml and 0.0881 ng/ml, P=0.374; troponin I=0.216 ng/ml and 0.707 ng/ml, P=0.357). The time course of troponins T and I levels in rejectors and nonrejectors do not differ with both groups having early elevations. Markers of myocyte death are inadequate predictors of acute rejection in cardiac allografts. The time course of troponins T and I suggests a possible role as prognostic indicators of outcome.

Analysis of risk factors for development of atrial fibrillation early after cardiac valvular surgery.

Atrial fibrillation (AF) commonly develops after cardiac valvular surgery. The objective of this study was to identify risk factors for postoperative AF following valvular surgery. A cohort of 915 consecutive adult patients undergoing isolated valvular surgery with preoperative sinus rhythm was analyzed. Univariate and independent multivariate risk factors for postoperative AF were determined. A second cohort of 305 patients with the same inclusion criteria was used to validate the multivariate predictors. Patients studied had a mean age of 56.1 +/- 14.7 years, 57.9% were men, 79.6% had a normal left ventricular ejection fraction, and their mean left atrial size was 46.2 +/- 9.3 mm. The incidence of postoperative AF was 36.7%. Independent predictors of postoperative AF included: advanced age (odds ratio [OR] 1.506 per decade, 95% confidence interval, [CI] 1.35 to 1.68, p = 0.0001); mitral stenosis (OR 2.066, CI 1.21 to 3.52, p = 0.0077); left atrial enlargement (OR 1.468, CI 1.07 to 2.01, p = 0.0165); use of systemic hypothermia (OR 0.572, CI 0.422 to 0.776, p = 0.0003); and a history of cardiac surgery (OR 0.676, CI 0.465 to 0.981, p = 0.0393). Among these variables, advanced age, mitral stenosis, and left atrial enlargement were confirmed as independent risk factors in the validation cohort.

Natural history of isolated bundle branch block.

The purpose of this study was to determine the long-term outcome of patients with bundle branch block (BBB) who have no clinical evidence of cardiovascular disease. Among 110,000 participants in a screening program, 310 subjects with BBB without apparent of suspected heart disease were identified. Their outcome after a mean follow-up of 9.5 years was compared with that of 310 similarly screened age- and sex-matched controls. Among the screened population, isolated right BBB was more prevalent than isolated left BBB (0.18% vs 0.1%, respectively; p<0.001), and the prevalence of each abnormality increased with age (p<0.001). Total actuarial survival was no different for those with left BBB or right BBB and their respective controls. Cardiac mortality, however, was increased in the left BBB group when compared with their controls (p=0.01, log rank test). Left BBB, but not right BBB, was associated with an increased prevalence of cardiovascular disease at the follow-up (21% vs 11%; p=0.04). In the absence of clinically overt cardiac disease, the presence of left BBB or right BB is not associated with increased overall mortality. Isolated left BBB is associated with an increased risk of developing overt cardiovascular disease and increased cardiac mortality.

Results of percutaneous transluminal coronary angioplasty in patients greater than or equal to 65 years of age (from the 1985 to 1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry).

The 1985 to 1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry series of 1,801 initial procedures included 486 patients age greater than or equal to 65 years (elderly). In comparison to younger patients, a greater proportion of elderly patients were women and had unstable angina. Elderly patients had more history of hypertension and more history of congestive heart failure. Although the elderly had more extensive vessel disease, the numbers of lesions and vessels attempted with PTCA were similar in the older and younger cohorts. Angiographic success rates were similar for all age groups. Although complication rates in the catheterization laboratory did not differ, patients greater than or equal to 65 years were much more likely to require emergency coronary artery bypass graft surgery (CABG) (5.4 vs 2.8%, p less than 0.05) or elective CABG (3.9 vs 1.6%, p less than 0.01). The in-hospital death rate was considerably higher among the elderly (3.1 vs 0.2%, p less than 0.01). At 2-year follow-up, symptomatic status and cumulative rates of myocardial infarction, CABG and repeat PTCA were similar for elderly and younger patients. The death rate after 2 years was higher among elderly patients (8.8% of patients greater than or equal to 65 years vs 2.9% of patients less than 65 years, p less than 0.01). When the relative risk of death for the elderly was adjusted for factors more prevalent among those greater than or equal to 65 years (history of congestive heart failure, multivessel disease, unstable angina, history of hypertension and female gender), the relative risk remained significant but was substantially reduced (from 3.3 to 2.4).