Long-term results of a randomized controlled trial analyzing the role of systematic pre-operative coronary angiography before elective carotid endarterectomy in patients with asymptomatic coronary artery disease.

OBJECTIVES: To evaluate the potential benefit of systematic preoperative coronary-artery angiography followed by selective coronary-artery revascularization on the incidence of myocardial infarction (MI) in patients undergoing carotid endarterectomy (CEA) without a previous history of coronary artery disease (CAD). METHODS: We randomised 426 patients who were candidates for CEA, with no history of CAD, a normal electrocardiogram (ECG), and a normal cardiac ultrasound. In group A (n = 216) all patients underwent coronary angiography before CEA. In group B (n = 210) CEA was performed without coronary angiography. Patients were not blinded for relevant assessments during follow-up. Primary end-point was the occurrence of MI at 3.5 years. The secondary end-point was the overall survival rate. Median length of follow-up was 6.2 years. RESULTS: In group A, coronary angiography revealed significant coronary artery stenosis in 68 patients (31.5%). Among them, 66 underwent percutaneous Intervention (PCI) prior to CEA and 2 received combined CEA and coronary-artery bypass grafting (CABG). Postoperatively, no MI was observed in group A, whereas 6 MI occurred in group B, one of which was fatal (p = .01). During the study period, 3 MI occurred in group A (1.4%) and 33 were observed in group B (15.7%), 6 of which were fatal. The Cox model demonstrated a reduced risk of MI for patients in group A receiving coronary angiography (HR,.078; 95% CI, 0.024-0.256; p < .001). In addition, patients with diabetes and patients <70 years presented with an increased risk of MI. Survival analysis at 6 years by Kaplan-Meier estimates was 95.6 ± 3.2% in Group A and 89.7 ± 3.7% in group B (Log Rank = 6.54, p = .01). CONCLUSIONS: In asymptomatic coronary-artery patients, systematic coronary angiography prior to CEA followed by selective PCI or CABG significantly reduces the incidence of late MI and increases long-term survival. (ClinicalTrials.gov number, NCT02260453).

A simple circuit for cerebral perfusion during cardiopulmonary bypass surgery of the ascending aorta and the aortic arch.

INTRODUCTION: A circuit was developed to allow for rapid reaction to the needs of perfusion during extracorporeal circulation (ECC) in surgery of the aortic arch and ascending aorta. METHOD: From January 2008 through January 2010, a home-designed circuit was used on 30 patients with aortic dissection who underwent surgery to replace the ascending aorta and the aortic arch and, in some cases, the aortic valve and re-implant of the coronary arteries using Bentall's technique.

Extracardiac left to right shunt in a patient with biventricular postinfarction rupture and pseudoaneurysm.

A 68 year old man had a diaphragmatic myocardial infarction and 9 months later was admitted with severe congestive heart failure (functional class IV). Cardiac catheterization demonstrated a postinfarction pseudoaneurysm. Because of a massive left to right shunt (pulmonary to systemic flow ratio = 2.7), concomitant rupture of the ventricular septum was suspected. At surgery the pseudoaneurysm communicated with the right ventricle through two different orifices and with the left ventricle through another ostium. The ventricular septum was intact. Therefore, the shunt was extracardiac through the pseudoaneurysm (left ventricle----pseudoaneurysm----right ventricle). The unique combination of lesions allowed the patient to survive. The false aneurysm was excised and primary repair was performed in the orifices of the right and left ventricular walls. The postoperative course was uneventful and 10 months later the patient was in functional class I.

Plasmid vectors for constructing translational fusions to the B subunit of cholera toxin.

A family of plasmid cloning vectors has been developed for creating translational fusions to the ctxB gene encoding the B subunit of cholera toxin (CTB) in Escherichia coli. These vectors permit insertion of transcriptionally and translationally competent gene sequences upstream from ctxB. To test the utility of the system, a portion of the glucosyltransferase B (GTF) gene (gtfB) from the cariogenic bacterium Streptococcus mutans GS-5 (Bratthall serotype c), encoding the N-terminal one-third of the protein, was inserted into each vector. E. coli lysates containing the constructs were partially purified by passage over a GM1 ganglioside affinity column. Western blotting analysis of the column retentate from one of the lysates revealed the presence of a novel 58-kDa protein which cross-reacted with antisera to GTF and CTB. These vectors are of general use for making other translational fusions to ctxB. The high binding affinity of CTB can be exploited in purifying large polypeptides fused to this relatively small protein. Moreover, these vectors can be used to create neoantigens with altered immunogenicity for use in polypeptide-based vaccines.

A cloning vector able to replicate in Escherichia coli and Streptococcus sanguis.

A plasmid that is able to replicate in both Escherichia coli and Streptococcus sanguis has been constructed by the in vitro joining of the pACYC184 (Cmr Tcr) and pVA749 (Emr) replicons. This plasmid, designated pVA838, is 9.2 kb in size and expresses Emr in both E. coli and S. sanguis. Its Cmr marker is expressed only in E. coli and may be inactivated by addition of DNA inserts at its internal EcoRI or PvuII sites. The pVA838 molecule also contains unique SalI, SphI, BamHI, NruI and XbaI cleavage sites suitable for molecular cloning. pVA838 may be amplified in E. coli but not in S. sanguis. We have used the pVA838 plasmid as a shuttle vector to clone streptococcal plasmid fragments in E. coli. Such chimeras isolated from E. coli were readily introduced into S. sanguis by transformation.

Novel shuttle plasmid vehicles for Escherichia-Streptococcus transgeneric cloning.

A novel plasmid vector that is able to replicate both in Escherichia coli and in Streptococcus sanguis is described. This 9.2-kb plasmid, designated pVA856, carries Cmr, Tcr, and Emr determinants that are expressed in E. coli. Only the Emr determinant is expressed in S. sanguis. Both the Cmr and the Tcr of pVA856 may be insertionally inactivated. This plasmid affords several different cleavage-ligation strategies for cloning in E. coli followed by subsequent introduction of chimeras into S. sanguis. In addition, we have modified a previously described E. coli-S. sanguis shuttle plasmid [pVA838; Macrina et al., Gene 19 (1982) 345-353], so that it is unable to replicate in S. sanguis. The utility of such a plasmid for cloning and selecting sequences enabling autonomous replication in S. sanguis is demonstrated.

Construction and immunologic evaluation of a Porphyromonas gingivalis subsequence peptide fused to hepatitis B virus core antigen.

Several proteins of Porphyromonas gingivalis contain multiple copies of a 47 amino acid conserved repeated sequence. A fusion protein was constructed in which the P. gingivalis peptide was fused to the carboxy terminus of the hepatitis B core protein. This fusion protein was expressed in Escherichia coli, purified, and used to vaccinate mice that were later challenged with P. gingivalis W83 using the mouse abscess model. Although the mice were not protected against bacterial challenge, Western blot analysis showed that sera from the mice and from rabbits immunized with the fusion protein reacted with a number of vesicle proteins from P. gingivalis W83. These data suggested that this peptide is recognized by the host's immune system but that the antibodies are not protective.

Sucrose-derived exopolymers have site-dependent roles in Streptococcus mutans-promoted dental decay.

We have constructed a panel of mutants of S. mutans V403 which are defective in one or more of the glucosyltransferase genes (gtfB, C or D) or the fructosyltransferase gene (ftf). These strains have been tested for virulence in a gnotobiotic rat caries model with reference to both buccal (smooth surface) and sulcal (pit and fissure) carious lesions. Our data suggest differing roles for degradable and non-degradable polymers at buccal and sulcal sites. Non-degradable polymers (made by products of the gtfB and C genes) contributed significantly to the severity of smooth surface lesions. However, our studies suggested their role in pit and fissure lesions was not as important as the role of degradable polymers. Specifically, a mutant deficient in the major insoluble glucan synthesizing activity (product of the gtfB gene) was 25% more cariogenic on sulcal surfaces than was the wild-type V403 strain. We propose that extracellular glucosyltransferases and fructosyltransferase compete for sucrose and that this competition influences pathogenicity at differing tooth sites.

Infectivity of a glucan synthesis-defective mutant of Streptococcus gordonii (Challis) in a rat endocarditis model.

Streptococcus gordonii, a member of the human indigenous oral microflora, colonizes smooth tooth surfaces and contributes to dental plaque formation. Although it is not recognized as being a cariogenic pathogen, it may cause endocarditis following invasion of the bloodstream. Using allelic exchange mutagenesis, we have constructed a mutant of S. gordonii (Challis) which is defective in its single functional glucosyltransferase gene and, hence, is unable to synthesize glucan exopolymers from sucrose. When examined in a rat endocarditis model, the sucrose-grown mutant did not differ significantly from S. gordonii wild-type, suggesting that glucan polymers did not contribute to infectivity. This result was in striking contrast to that previously observed with a polymer-defective S. mutans mutant.

Graduate teaching in principles of scientific integrity.

Training in the responsible conduct of research in the biomedical sciences is on its way to being a standard component in the graduate biomedical curriculum. Emphasis in this area has been catalyzed by certain requirements for such training imposed by the National Institutes of Health and by an increased awareness of relevant issues created by the publicity and discussion of incidents of scientific misconduct. The authors describe the development and formalization of a course about the responsible conduct of science for students in the biomedical disciplines at Virginia Commonwealth University. In addition, they discuss general considerations of course content important in teaching scientific integrity; examine the use of published resource materials and documents from professional societies, institutions, states, and the federal government as teaching tools; and describe the importance of case studies as vehicles for teaching scientific integrity.

Nitroglycerin-induced changes in myocardial sestamibi uptake to detect tissue viability: radionuclide comparison before and after revascularization.

BACKGROUND: Nitroglycerin (NTG) is known to increase the blood supply to the myocardium, and would thus increase the delivery of a perfusional tracer such as sestamibi (MIBI) to the tissue. The latter, in turn, would take up and concentrate the tracer to a greater extent than in basal conditions only if energy-dependent mechanisms were still available-that is, only if the cells were still viable. METHODS: We evaluated the changes that intravenous administration of NTG induced on the uptake of MIBI by akinetic myocardial areas, using tomographic perfusional imaging in 23 patients with previously ascertained anterior myocardial infarction who were undergoing myocardial revascularization procedures. Changes in uptake were compared with echocardiographic and perfusional changes occurring after operation. RESULTS: The improvement of MIBI uptake after NTG correctly identified 12 of the 16 patients (75%) showing postoperative wall motion improvement; they comprised 12 of the 14 (86%) patients with NTG-induced increase in MIBI uptake who showed improved wall motion after operation. A close correlation (r = 0.88, P < 0.001) was found between the increase in myocardial MIBI uptake induced by NTG infusion and that induced by revascularization. The presence of collaterals to the akinetic area was associated with a significantly (P < 0.01) greater increase in MIBI uptake both during NTG infusion and after operation. CONCLUSIONS: The results of this study suggest that MIBI perfusional myocardial scintigraphy during infusion of NTG is capable of detecting viable but chronically hypoperfused myocardium, predicting postoperative wall motion and perfusional improvement, and reflecting the postoperative pattern of perfusion. The best results were achieved in patients with evidence of collateral circulation supplying the infarcted area.

Left ventricular aneurysmectomy; comparison between two techniques; early and late results.

OBJECTIVE: The aim of the present study was to evaluate early and late results of two different surgical techniques for left ventricular aneurysms repair. The conventional aneurysmectomy and direct closure of the ventricular wall and the endoventricular patch plasty. METHODS: We retrospectively reviewed 118 patients operated on for postinfarction left ventricular aneurysm from 1981 to 1994. Eighty-seven patients (Group A) were operated upon between 1981 and 1991 with the conventional technique and 31 patients (Group B) between 1992 and 1994 with the endoventricular patch plasty technique. Preoperative clinical, hemodynamic and echocardiographic evaluation with operative procedures and early postoperative results of all patients are reported. We also analyzed results of late clinical and echocardiographic controls of 34 patients of Group A and all patients of Group B after a mean follow-up of 42 and 28 months, respectively. RESULTS: Mean number of by-pass grafts was 1.9 in Group A and 2.6 in Group B (P = 0.01). The left anterior descending coronary artery was revascularized in 27 patients of Group A (34.6%) and 26 of Group B (89.7%) (P < 0.001); the left internal mammary artery was used in seven patients of Group A (8.9%) and 24 of Group B (82.8%) (P < 0.001). Hospital mortality in Group A was 10.3% (9/87), in Group B there was no hospital mortality (P > 0.05). Thirty-two patients of Group A (36.8%) and 3 of Group B (9.7%) suffered of low cardiac output syndrome (P = 0.01). At late control, improvements observed in NYHA and CCS classes, left ventricular ejection fraction (all P < 0.001 in both groups versus preoperative values) and left ventricular end-diastolic diameter (P > 0.05 in Group A and P < 0.001 in Group B) proved to be statistically higher in patients of Group B. CONCLUSIONS: Endoventricular patch plasty associated with a complete myocardial revascularization, in particular of the anterior descending coronary, and a larger use of the internal mammary artery, permits, by means of reconstruction of the left ventricular geometry, a better outcome for patients undergoing left ventricular aneurysmectomy.

Extrachromosomal gene systems in Streptococcus mutans.

1) Four of 86 S. mutans strains of human origin harbor a 3.6 Mdal multicopy plasmid while 2 of 13 strains of rat origin carry multiple copies of a 2.3 Mdal and 2.5 Mdal plasmid. 2) There is no evidence to support that any of these plasmids confers clinically or ecologically important phenotypes. 3) The restriction endonucleases Hind III and Bam HI cleave the 3.6 Mdal plasmid once, thus facilitating the use of this extrachromosomal element in gene cloning systems.

Liposomes and conjugate vaccines for antigen delivery and induction of mucosal immune responses.

In this brief review, emphasis was placed on the effectiveness of liposomes as carriers/vehicles of soluble antigens and as adjuvants for use in oral vaccine development. Evidence was provided that oral administration of antigen in liposomes resulted in a mucosal response which was higher than that obtained when the oral vaccine consisted of antigen alone. Specific mucosal responses were enhanced by incorporating lipophilic MDP into the antigen/liposome vaccines. Antigens shown to be effective in inducing a protective mucosal response when given in an oral liposome vaccine were anti-idiotypic antibodies, purified S. mutans GTF, CHO and Ag I/II. Evidence is also provided that CTB may be an effective oral adjuvant when coupled to proteins or peptides by either chemical or genetic methods. Further studies, however, will be required to characterize the effectiveness and safety of CTB in conjugate vaccines for inducing specific mucosal responses and to develop practical means to prepare oral liposome vaccines for use in humans.

Left ventricular thrombosis after blunt chest trauma.

A 22-year-old man was admitted to our observation with left ventricular thrombus arising after blunt chest trauma occurring during a ski accident one year before. None was obtained from a review of instrumental and laboratory data at trauma time. Transesophageal echocardiography showed an intraventricular thrombus and severe hypokinesia at the apex. Standard cardiac surgery procedure was performed and postoperative period was uneventful. Echocardiography controls at 6/12 months showed a normal apex kinesia. This case shows the importance of hospitalization, hemodynamics monitorization and late serial echocardiographic controls for timely diagnosis and management of myocardial contusion and consecutive ventricular thrombus formation to prevent life-threatening complications.

Factors influencing immediate and long-term results after button's technique.

BACKGROUND: Aim of this study was to evaluate the factors influencing immediate and long-term results in patients undergoing aortic root replacement with a composite graft. METHODS: Between January 1989 and February 1999, 105 patients (83 males, 22 females) who underwent Bentall technique were studied. Preoperative diagnosis was annulo-aortic ectasia in 54, aortic dissection in 27, atherosclerotic aneurysm in 21, and aortitis in 3 cases. Seventeen patients were affected by Marfan's syndrome. All cases, elective, urgent, and emergency were included. Button technique was performed and the associated surgical procedures were coronary artery bypass grafting in 21, total aortic arch replacement in 15, proximal hemi arch in 5, and mitral valve replacement in 5 cases. RESULTS: The overall hospital mortality rate was 7.6% (n=8). Univariate analysis using chi(2) and/or two-sample "t"-test showed that dissection, aortitis, aneurysm rupture into-pleura or pericardium, emergency status, redo, prolonged pump times and circulatory arrest, were predictors influencing in-hospital mortality. Coagulopathy, low cardiac output, stroke, perioperative myocardial infarction, surgical bleeding leading to reoperation, were significantly related to in-hospital mortality (by correlation analysis). A multivariate analysis showed that, emergency status (p=0.027), aortic dissection (p=0.029), perioperative myocardial infarction (p=0.0021), reoperation for bleeding (p=0.0023), and pump time >180 min (p=0.011), were significant. The actuarial survival rate at 10 years follow-up was 84.7%. There were 8 late deaths. The Kaplan-Meier showed significant differences when considering dissection vs non-dissection (p=0.018), but did not reach significance in Marfan vs non-Marfan groups (p=0.83). NYHA class IV (p=0.052), previous cardiac surgery procedure (p=0.041), concomitant CABG (p=0.021), total aortic arch reconstruction (p=0.001), and mitral valve replacement (p=0.016), were identified as significant by Log Rank test. CONCLUSIONS: The Bentall procedure for aortic root replacement is safe and durable; in hospital mortality in elective status it was 1.28%; early and long-term mortality higher in patients with acute dissection. Six late deaths were procedures related. Sixty-six patients (76.4%) were in NYHA I class at follow-up. The incidence of late outcomes, thromboembolism (1.03%), graft infection (2.06%), pseudoaneurysm (0%), reoperation in ascending aorta or aortic valve (3.1%), operations on the remaining aorta (6.7%), and hemorrhage due to anticoagulant therapy (1.03%), are very low.

Iliac arteriovenous fistula complicating lumbar laminectomy.

An iliac arteriovenous fistula may rarely complicate lumbar laminectomy, particularly at the L4-L5 level. We present such a complication in a 45-year-old man who presented in our institution with a postlaminectomy iliac arteriovenous fistula and severe congestive heart failure. Repair of the fistulous orifice and tubular reconstruction of the iliac artery were successfully performed.

The case study approach to teaching scientific integrity in nursing and the biomedical sciences.

Scientific integrity courses for graduate trainees are emerging at many institutions. The content of such courses varies and is evolving as faculty strive to meet the needs of their specific student audiences. Typical course subject matters include responsible authorship, conflict of interest, handling of scientific misconduct, data management, and the use of humans and animals in biomedical experimentation. These and other topic areas are amenable to teaching methods that use the case study approach. In this article we discuss our experiences in teaching scientific integrity using the case study approach. Issues covered include underlying philosophy of the approach, preparation and use of cases, desired inclass preparation and teaching. Examples of short cases are presented and, where appropriate, discussed in the context of these issues.